supplementary online content · 2 eappendix authors: su-hsin chang phd1, carolyn r.t. stoll mph,...

1

Supplementary Online Content

Chang S-H, Stoll CRT, Song J, Varela JE, Eagon CJ, Colditz GA. The effectiveness and risks of bariatric surgery: an updated systematic review and meta-analysis, 2003-2012. JAMA Surg. Published online December 18, 2013. doi:10.1001/jamasurg.2013.3654.

eAppendix.

eFigure 1. Network diagram.

eFigure 2. Funnel plots with pseudo 95% confidence limits and Egger’s test results.

eTable 1. Definitions of comorbid conditions and comorbidity improvement.

eTable 2. Summary of surgery types and classes.

eTable 3. Meta-analyses of surgery risk and comorbidities remission outcomes.

eTable 4. Meta-analyses of weight change outcomes.

eTable 5. Meta-regression results.

eTable 6. MTC Model 1 estimates: relative surgery effects (∆BMI) to LRYGB.

eTable 7. MTC Model 2 estimates: relative surgery effects (∆BMI) to LRYGB.

eTable 8. MTC Model 3 estimates: relative surgery category effects (∆BMI) to GB.

eTable 9. MTC Model 4 estimates: time-varying relative surgery effects (∆BMI) to LRYGB.

eTable 10. A comparison of findings across the systematic reviews and meta-analyses of bariatric surgery.

This supplementary material has been provided by the authors to give readers additional information about their work.

Downloaded From: https://jamanetwork.com/ by a Non-Human Traffic (NHT) User on 10/04/2020

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eAppendix

Authors: Su-Hsin Chang PhD1, Carolyn R.T. Stoll MPH, MSW 1, Jihyun Song PhD 2, J. Esteban Varela MD MPH FACS3, Christopher J. Eagon MD3, Graham A. Colditz MD DrPH1 1. Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine2. School of Management, New York Institute of Technology3. Minimally Invasive and Bariatric Surgery, Department of Surgery, Washington University School of Medicine

Corresponding Author:

Su-Hsin Chang, PhD Division of Public Health Sciences, Department of Surgery Washington University School of Medicine 660 S. Euclid Avenue, Campus Box 8100 St. Louis, MO 63110 Email: [email protected] Phone: (314) 362-8623 Cell phone: (410) 209-7926

1. Search terms

2. Models used to estimate operative mortality and complication rates and remission rate of the obesity-attributablecomorbidities

3. Mixed treatment comparison (MTC) of repeated measurement meta-analysis

4. Estimation results

1. Search terms

PubMed

“Bariatric surgery”[Mesh] OR “bariatric surgery” OR “bariatric surgeries” OR “Gastric bypass” [Mesh] OR “roux-en-y gastric bypass” OR “greenville gastric bypass” OR “gastroileal bypass” OR “gastrojejunostomy” OR “gastrojejunostomies” OR “gastroplasty”[Mesh] OR “gastroplasties” OR “collis gastroplasty” OR “vertical-banded gastroplasty” OR “vertical banded gastroplasty” OR “vertical-banded gastroplas” OR “Jejunoileal bypass”[Mesh] OR “jejunoileal bypass” OR “jejunoileal bypass” OR “jejuno-ileal bypasses” OR “ileojejunal bypass” OR “ileojejunal bypasses” OR “intestinal bypass” OR “intestinal bypasses” OR “lipectomy”[Mesh] OR “lipectomies” OR “aspiration lipectomy” OR “aspiration lipolysis” OR “suction lipectomy” OR “suction lipectomies” OR “ suction lipolysis” OR “liposuction” OR “liposuctions” OR “lipoplasty” OR “lipoplasties” OR “biliopancreatic bypass” OR “biliopancreatic diversion” OR “ duodenal switch” OR “pancreatobiliary bypass” OR “gastric banding” OR “ Stomach banding” OR “swedish gastric banding” OR “swedish adjustable gastric banding” OR “ laparoscopic adjustable gastric banding” OR “laparoscopic adjustable silicone banding” OR “bariatric operation” OR “ bariatric operations” OR “ bariatric procedure” OR “ bariatric procedures” OR “bariatric surgical procedure” OR “ bariatric surgical procedures” OR “obesity surgery” Or “sleeve gastrectomy” OR “gastric sleeve”

"Body Mass Index"[Mesh] OR "Body Mass Index" OR “Quetelet Index” OR “Quetelets Index” OR “BMI” OR “body ban mass”

Comorbidities – diabetes, coronary heart disease, hypertension, dyslipidemia, stroke, sleep apnea


3

“diabetes mellitus type 2” [Mesh] OR “Ketosis-Resistant Diabetes Mellitus” OR “Diabetes Mellitus Maturity-Onset” OR “Diabetes Mellitus Maturity Onset” OR “Non-Insulin-Dependent Diabetes Mellitus” OR “Type 2 Diabetes Mellitus” OR “Slow-Onset Diabetes Mellitus” OR “Stable Diabetes Mellitus” OR “Diabetes Mellitus Type II” OR “MODY” OR “NIDDM” OR “Adult-Onset Diabetes Mellitus” OR “lipoatrophic diabetes mellitus” OR “type 2 diabetes” OR “type II diabetes” OR “dm 2” OR “insulin independent diabetes” OR “insulin independent diabetes mellitus” OR “ketosis resistant diabetes mellitus” OR “non insulin dependent diabetes” OR “non insulin dependent diabetes mellitus” OR “type 2 diabetes mellitus ”

“cardiovascular diseases”[Mesh] OR “cardiovascular diseases” OR “cardiovascular disease” OR “cardiovascular abnormalities” OR “cardiovascular infections” OR “Heart diseases” OR “vascular diseases” OR “coronary artery insufficiency” OR “coronary artery occlusive disease” OR “coronary heart disease” OR “coronary insufficiency” OR “coronary occlusive disease” OR “ischemic heart disease” OR “ischaemic heart disease” OR “ ischemic heart disease” OR “ischemic cardiac disease” OR “ ischemic cardial disease” OR “ ischemic cardiopathy”

“sleep apnea obstructive”[Mesh] OR “obstructive sleep apnea” OR “obesity hypoventilation syndrome” OR “Upper Airway Resistance Sleep Apnea Syndrome” OR “obstructive sleep apnea syndrome” OR “sleep apnea” OR “nocturnal apnea” OR “obstructive sleep apnea hypopnea syndrome” OR “obstructive sleep apnoea”

“hypertension”[Mesh] OR “hypertension” OR “high blood pressure” OR “high blood pressures” OR “hypertension malignant” OR “ hypertension renal” OR “hypertensive retinopathy” OR “masked hypertension” OR “white coat hypertension” OR “acute hypertension” OR “ arterial hypertension” OR “cardiovascular hypertension” OR “controlled hypertension” OR “endocrine hypertension” OR “high renin hypertension” OR “hypertensive disease” OR “hypertensive effect” OR ” hypertensive response” OR “ increased blood pressure” OR “neurogenic hypertension” OR ”preexistent hypertension” OR” refractory hypertension” OR “salt high blood pressure” OR “salt hypertension” OR “secondary hypertension” OR “systemic hypertension”

“dyslipidemais”[Mesh] OR “dyslipidemia” OR “hyperlipidemias” OR “Hypolipoproteinemias” OR ”Smith-Lemli-Opitz Syndrome” OR “dyslipoproteinemias” OR “dyslipoproteinemia” OR “dys lipidemia”

“stroke”[Mesh] OR “stroke” OR “strokes” OR “cerebral stoke” OR “cerebral strokes” OR “brain vascular accident” OR “brain vascular accidents” OR “cerebrovascular apoplexy” OR “cerebrovascular stroke” OR “cerebralvascular strokes” OR “CVA” OR “CVAs” OR “apoplexy” OR “ ceberovascular accident” OR “ cerebrovascular accidents” OR “acute cerebrovascular accident” OR “acute cerebrovascular accidents” OR “brain infarction” OR “lacunar stroke” OR “acute cerebrovascular lesion” OR “acute focal cerebral vasculopathy” OR “apoplectic stroke” OR “apoplexia” OR “brain blood flow disturbance” OR “brain accident” OR “ brain attack” OR “brain insult” OR “brain insults” OR “brain ischemic attack” OR “cerebral apoplexia” OR “cerebral insult” OR “cerebral vascular accident” OR “cerebral vascular insufficiency” OR “cerebro vascular accident” OR “cerebrovascular arrest” OR “cerebrovascular failure” OR “cerebrovascular injury” OR “cerebrovascular insufficiency” OR “cerebrovascular insult” OR “cerebrovascular trauma” OR “cerebrum vascular accident” OR “ischaemic seizure” OR “ischemic cerebral attack” OR “ ischemic seizure”

Study design

“controlled clinical trial” OR “randomized controlled trial” OR ”controlled clinical trial” OR “randomized controlled trial” OR “groups” OR “trial” OR “randomly” OR “randomized”

Limits

NOT ((“animals” [Mesh] NOT (“Animals”[Mesh] AND “humans”[Mesh]))


4

Search: (("controlled clinical trial" OR "randomized controlled trial" OR "controlled clinical trial" OR "randomized controlled trial" OR "groups" OR "trial" OR "randomly" OR "randomized")) AND ((((((((("diabetes mellitus type 2"[Mesh] OR "Ketosis-Resistant Diabetes Mellitus" OR "Diabetes Mellitus Maturity-Onset" OR "Diabetes Mellitus Maturity Onset" OR "Non-Insulin-Dependent Diabetes Mellitus" OR "Type 2 Diabetes Mellitus" OR "Slow-Onset Diabetes Mellitus" OR "Stable Diabetes Mellitus" OR "Diabetes Mellitus Type II" OR "MODY" OR "NIDDM" OR "Adult-Onset Diabetes Mellitus" OR "lipoatrophic diabetes mellitus" OR "type 2 diabetes" OR "type II diabetes" OR "dm 2" OR "insulin independent diabetes" OR "insulin independent diabetes mellitus" OR "ketosis resistant diabetes mellitus" OR "non insulin dependent diabetes" OR "non insulin dependent diabetes mellitus" OR "type 2 diabetes mellitus ")) OR ("cardiovascular diseases"[Mesh] OR "cardiovascular diseases" OR "cardiovascular disease" OR "cardiovascular abnormalities" OR "cardiovascular infections" OR "Heart diseases" OR "vascular diseases" OR "coronary artery insufficiency" OR "coronary artery occlusive disease" OR "coronary heart disease" OR "coronary insufficiency" OR "coronary occlusive disease" OR "ischemic heart disease" OR "ischaemic heart disease" OR "ischemic heart disease" OR "ischemic cardiac disease" OR "ischemic cardial disease" OR "ischemic cardiopathy")) OR ("sleep apnea obstructive"[Mesh] OR "obstructive sleep apnea" OR "obesity hypoventilation syndrome" OR "Upper Airway Resistance Sleep Apnea Syndrome" OR "obstructive sleep apnea syndrome" OR "sleep apnea" OR "nocturnal apnea" OR "obstructive sleep apnea hypopnea syndrome" OR "obstructive sleep apnoea")) OR ("dyslipidemias"[Mesh] OR "dyslipidemia" OR "hyperlipidemias" OR "Hypolipoproteinemias" OR "Smith-Lemli-Opitz Syndrome" OR "dyslipoproteinemias" OR "dyslipoproteinemia" OR "dys lipidemia")) OR ("stroke"[Mesh] OR "stroke" OR "strokes" OR "cerebral stoke" OR "cerebral strokes" OR "brain vascular accident" OR "brain vascular accidents" OR "cerebrovascular apoplexy" OR "cerebrovascular stroke" OR "cerebralvascular strokes" OR "CVA" OR "CVAs" OR "apoplexy" OR "ceberovascular accident" OR "cerebrovascular accidents" OR "acute cerebrovascular accident" OR "acute cerebrovascular accidents" OR "brain infarction" OR "lacunar stroke" OR "acute cerebrovascular lesion" OR "acute focal cerebral vasculopathy" OR "apoplectic stroke" OR "apoplexia" OR "brain blood flow disturbance" OR "brain accident" OR "brain attack" OR "brain insult" OR "brain insults" OR "brain ischemic attack" OR "cerebral apoplexia" OR "cerebral insult" OR "cerebral vascular accident" OR "cerebral vascular insufficiency" OR "cerebro vascular accident" OR "cerebrovascular arrest" OR "cerebrovascular failure" OR "cerebrovascular injury" OR "cerebrovascular insufficiency" OR "cerebrovascular insult" OR "cerebrovascular trauma" OR "cerebrum vascular accident" OR "ischaemic seizure" OR "ischemic cerebral attack" OR "ischemic seizure")) OR ("quality of life"[Mesh] OR "life style" OR "sickness impact profile" OR "value of life" OR "karnnofsky performance status" OR "activities of daily living"[Mesh] OR "daily living activities" OR "daily living activity" OR "ADL" OR "chronic limitation of activity" OR "self care" OR "self cares" OR "walking"[Mesh] OR "walking " OR "ambulation" OR "mobility limitations"[Mesh] OR "mobility limitations" OR "ambulation difficulty" OR "difficulty walking" OR "ambulatory difficulty"))) AND ((("Bariatric surgery"[Mesh] OR "bariatric surgery" OR "bariatric surgeries" OR "Gastric bypass"[Mesh] OR "roux-en-y gastric bypass" OR "greenville gastric bypass" OR "gastroileal bypass" OR "gastrojejunostomy" OR "gastrojejunostomies" OR "gastroplasty"[Mesh] OR "gastroplasties" OR "collis gastroplasty" OR "vertical-banded gastroplasty" OR "vertical banded gastroplasty" OR "vertical-banded gastroplas" OR "Jejunoileal bypass"[Mesh] OR "jejunoileal bypass" OR "jejunoileal bypass" OR "jejuno-ileal bypasses" OR "ileojejunal bypass" OR "ileojejunal bypasses" OR "intestinal bypass" OR "intestinal bypasses" OR "lipectomy"[Mesh] OR "lipectomies" OR "aspiration lipectomy" OR "aspiration lipolysis" OR "suction lipectomy" OR "suction lipectomies" OR "suction lipolysis" OR "liposuction" OR "liposuctions" OR "lipoplasty" OR "lipoplasties" OR "biliopancreatic bypass" OR "biliopancreatic diversion" OR "duodenal switch" OR "pancreatobiliary bypass" OR "gastric banding" OR "Stomach banding" OR "swedish gastric banding" OR "swedish adjustable gastric banding" OR "laparoscopic adjustable gastric banding" OR "laparoscopic adjustable silicone banding" OR "bariatric operation" OR "bariatric operations" OR "bariatric procedure" OR "bariatric procedures" OR "bariatric surgical procedure" OR "bariatric surgical procedures" OR "obesity surgery" OR "sleeve gastrectomy" OR "gastric sleeve")) AND ("Body Mass Index"[Mesh] OR "Body Mass Index" OR "Quetelet Index" OR "Quetelets Index" OR "BMI" OR "body ban mass"))) NOT (("animals"[MESH] NOT ("animals")[MESH] AND "humans"[MESH]))


5

EMBASE

‘Bariatric surgery’/exp OR ‘bariatric operation’ OR ‘ bariatric operations’ OR ‘ bariatric procedure’ OR ‘bariatric procedures’ OR ‘ bariatric surgical procedure’ OR ‘ bariatric surgical procedures’ OR ‘obesity surgery’ OR ‘sleeve gastrectomy’/exp OR ‘sleeve gastrectomy’ OR ‘gastric sleeve’ OR ‘biliopancreatic bypass’/exp OR ‘biliopancreatic diversion’ OR ‘duodenal switch’ OR ‘pancreatobiliary bypass’ OR ‘gastric banding’/exp OR ‘gastric banding’ OR ‘stomach banding’ OR ‘swedish gastric banding’ OR ‘swedish adjustable gastric banding’ OR ‘laparoscopic adjustable gastric banding’ OR ‘laparoscopic adjustable silicone banding’ OR ‘bariatric surgery’ OR ‘bariatric surgeries’ OR ‘Gastric bypass’ OR ‘roux-en-y gastric bypass’ OR ‘greenville gastric bypass’ OR ‘gastroileal bypass’ OR ‘gastrojejunostomy’ OR ‘gastrojejunostomies’ OR ‘gastroplasty’ OR ‘gastroplasties’ OR ‘collis gastroplasty’ OR ‘vertical-banded gastroplasty’ OR ‘vertical banded gastroplasty’ OR ‘vertical banded gastroplasties’ OR ‘jejunoileal bypass’ OR ‘jejuno ileal bypass’ OR ‘ileojejunal bypass’ OR ‘ileojejunal bypasses’ OR ‘intestinal bypass’ OR ‘intestinal bypasses’ OR ‘lipectomy’ OR ‘lipectomies’ OR ‘aspiration lipectomy’ OR ‘aspiration lipolysis’ OR ‘suction lipectomy’ OR ‘suction lipectomies’ OR ‘suction lipolysis’ OR ‘liposuction’ OR ‘liposuctions’ OR ‘lipoplasty’ OR ‘lipoplasties’

AND

'body mass'/exp OR ‘body mass’ OR ‘Body Mass Index’ OR ‘Quetelet Index’ OR ‘Quetelets Index’ OR ‘BMI’ OR ‘body ban mass’

AND

Comorbidities - diabetes, coronary heart disease, hypertension, dyslipidemia, stroke, sleep apnea

AND

‘non insulin dependent diabetes mellitus’/exp OR ‘diabetes mellitus type 2’ OR ‘Ketosis Resistant Diabetes Mellitus’ OR ‘Diabetes Mellitus Maturity Onset’ OR ‘Non Insulin Dependent Diabetes Mellitus’ OR ‘Type 2 Diabetes Mellitus’ OR ‘Slow Onset Diabetes Mellitus’ OR ‘Stable Diabetes Mellitus’ OR ‘Diabetes Mellitus Type II’ OR ‘MODY’ OR ‘NIDDM’ OR ‘Adult Onset Diabetes Mellitus’ OR ‘lipoatrophic diabetes mellitus’ OR ‘type 2 diabetes’ OR ‘type II diabetes’ OR ‘dm 2’ OR ‘insulin independent diabetes’ OR ‘insulin independent diabetes mellitus’ OR ‘non insulin dependent diabetes’

OR

‘ischemic heart disease’/exp OR ‘ischaemic heart disease’ OR ‘ ischemic heart disease’ OR ‘ischemic cardiac disease’ OR ‘ischemia heart disease’ OR ‘ischemic cardial disease’ OR ‘ ischemic cardiopathy’ OR ‘acute coronary syndrome’ OR ‘angina pectoris’ OR ‘cardiac allograft vasculpathy’ OR ’coronary artery atheroscloerosis’ OR ‘coronary artery constriction’ OR ‘ coronary artery obstruction’ OR ‘ cornary artery obstruction’ OR ‘coronary artery thrombosis’ OR ‘coronary subclavian steal syndrome’ OR ‘heart infarction’ OR ‘ heart muscle ischemia’ OR ‘ ischemic cardiomyopathy’ OR ‘kounis syndrome’ OR ‘myocardial hibernation’ OR ‘no reflow phenomenon’ OR ‘silent myocardial ischemia’ OR ‘takotsubo cadriomyopathy’ OR ‘cardiovascular diseases’ OR ‘cardiovascular disease’ OR ‘cardiovascular abnormalities’ OR ‘cardiovascular infections’ OR ‘heart diseases’ OR ‘vascular diseases’ OR ‘coronary artery insufficiency’ OR ‘coronary artery occlusive disease’ OR ‘coronary heart disease’

OR

‘Sleep Apnea Syndrome’/exp OR ‘obstructive sleep apnea’ OR ‘obesity hypoventilation syndrome’ OR ‘Upper Airway Resistance’ OR ‘obstructive sleep apnea syndrome’ OR ‘sleep apnea’ OR ‘nocturnal apnea’ OR ‘obstructive sleep apnea hypopnea syndrome’ OR ‘obstructive sleep apnoea’

OR


6

‘Hypertension‘/exp OR ‘apparent mineralocorticoid excess syndrome’ OR ‘borderline hypertension’ OR ‘borderline hypertension’ OR ‘diabetic hypertension’ OR ‘essential hypertension’ OR ‘gordon syndrome’ OR ‘hereditary hypertension’ OR ‘hypertensive crisis’ OR ‘intracranial hypertension’ OR ‘liddle syndrome’ OR ‘malignant hypertension’ OR ‘maternal hypertension’ OR ‘metabolic syndrome x’ OR ‘ocular ischemic syndrome’ OR ‘orthostatic hypertension’ OR ‘posterior reversible encephalopathy syndrome’ OR ‘prehypertension’ OR ‘renovascular hypertension’ OR ‘systolic hypertension’ OR ‘hypertension’ OR ‘high blood pressure’ OR ‘high blood pressures’ OR ’hypertension malignant’ OR ‘ hypertension renal’ OR ‘hypertensive retinopathy’ OR ‘masked hypertension’ OR ‘white coat hypertension’ OR ‘acute hypertension’ OR ‘arterial hypertension’ OR ‘cardiovascular hypertension’ OR ‘controlled hypertension’ OR ‘endocrine hypertension’ OR ‘high renin hypertension’ OR ‘hypertensive disease’ OR ‘hypertensive effect’ OR ‘hypertensive response’ OR ‘increased blood pressure’ OR ‘neurogenic hypertension’ OR ‘preexistent hypertension’ OR ’refractory hypertension’ OR ‘salt high blood pressure’ OR ‘salt hypertension’ OR ‘secondary hypertension’ OR ‘systemic hypertension’

OR

‘dyslipidemias’ OR ‘dyslipidemia’/exp OR ’dyslipidemia’ OR ’hyperlipidemias’ OR ‘Hypolipoproteinemias’ OR ‘Smith Lemli Opitz Syndrome’ OR ‘dyslipoproteinemias’ OR ‘dyslipoproteinemia’ OR ‘dyslipidemia’

OR

‘stroke’/exp OR ‘lacunar stroke’ OR ‘stroke’ OR ‘cerebral stoke’ OR ‘cerebral strokes’ OR ‘brain vascular accident’ OR ‘brain vascular accidents’ OR ‘cerebrovascular apoplexy’ OR ‘cerebrovascular stroke’ OR ‘cerebralvascular strokes’ OR ‘CVA’ OR ‘CVAs’ OR ‘apoplexy’ OR ‘ ceberovascular accident’ OR ‘cerebrovascular accidents’ OR ‘acute cerebrovascular accident’ OR ‘acute cerebrovascular accident’ OR ‘brain infarction’ OR ‘acute cerebrovascular lesion’ OR ‘acute focal cerebral vasculopathy’ OR ‘apoplectic stroke’ OR ‘apoplexia’ OR ‘brain blood flow disturbance’ OR ‘brain accident’ OR ‘brain attack’ OR ‘brain insult’ OR ‘brain insults’ OR ‘brain ischemic attack’ OR ‘cerebral apoplexia’ OR ‘cerebral insult’ OR ‘cerebral vascular accident’ OR ‘cerebral vascular insufficiency’ OR ‘cerebro vascular accident’ OR ‘cerebrovascular arrest’ OR ‘cerebrovascular failure’ OR ‘cerebrovascular injury’ OR ‘cerebrovascular insufficiency’ OR ‘cerebrovascular insult’ OR ‘cerebrovascular trauma’ OR ‘cerebrum vascular accident’ OR ‘ischaemic seizure’ OR ‘ischemic cerebral attack’ OR ‘ischemic seizure’

Study design

‘controlled clinical trial’/it OR ‘randomized controlled trial’/it OR 'controlled clinical trial'/exp OR 'randomized controlled trial'/exp OR (groups OR trial OR randomly OR randomized):ab OR (groups OR trial OR randomly OR randomized):ti

Limits

Not ([animals]/lim NOT [humans]/lim) AND [English]/lim

SCOPUS

{Bariatric surgery} OR {bariatric operation} OR {bariatric operations} OR {bariatric procedure} OR {bariatric procedures} OR { bariatric surgical procedure} OR {bariatric surgical procedures} OR {obesity surgery} OR {sleeve gastrectomy} OR {gastric sleeve} OR {biliopancreatic bypass} OR {biliopancreatic diversion} OR {duodenal switch} OR {pancreatobiliary bypass} OR {gastric banding} OR {gastric banding} OR {stomach banding} OR {swedish gastric banding} OR {swedish adjustable gastric banding} OR {laparoscopic adjustable gastric banding} OR {laparoscopic adjustable silicone banding} OR {bariatric surgeries} OR {Gastric bypass} OR {roux-en-y gastric bypass} OR {greenville gastric bypass} OR {gastroileal bypass} OR {gastrojejunostomy} OR {gastrojejunostomies} OR {gastroplasty} OR {gastroplasties} OR {collis gastroplasty} OR {vertical-banded gastroplasty} OR {vertical banded gastroplasty} OR {vertical banded gastroplasties} OR {jejunoileal bypass} OR {jejuno ileal bypass} OR {ileojejunal bypass} OR {ileojejunal bypasses} OR {intestinal bypass} OR {intestinal bypasses} OR {lipectomy} OR {lipectomies} OR {aspiration lipectomy} OR {aspiration lipolysis} OR


7

{suction lipectomy} OR {suction lipectomies} OR {suction lipolysis} OR {liposuction} OR {liposuctions} OR {lipoplasty} OR {lipoplasties}

{body mass} OR {body mass} OR {Body Mass Index} OR {Quetelet Index} OR {Quetelets Index} OR {BMI} OR {body ban mass}

Comorbidities - diabetes, coronary heart disease, hypertension, dyslipidemia, stroke, sleep apnea

{non-insulin dependent diabetes mellitus} OR {diabetes mellitus type 2} OR {Ketosis Resistant Diabetes Mellitus} OR {Diabetes Mellitus Maturity Onset} OR ‘{non-Insulin Dependent Diabetes Mellitus} OR {Type 2 Diabetes Mellitus} OR {Slow Onset Diabetes Mellitus} OR ‘{table Diabetes Mellitus} OR {Diabetes Mellitus Type II} OR {MODY’ OR ‘NIDDM} OR {Adult Onset Diabetes Mellitus} OR {lipoatrophic diabetes mellitus} OR {type 2 diabetes} OR {type II diabetes} OR {dm 2} OR {insulin independent diabetes} OR {insulin independent diabetes mellitus} OR {non-insulin dependent diabetes}

{ischemic heart disease} OR {ischaemic heart disease} OR {ischemic heart disease} OR {ischemic cardiac disease} OR {ischemia heart disease} OR {ischemic cardial disease} OR {ischemic cardiopathy} OR {acute coronary syndrome} OR {angina pectoris} OR {cardiac allograft vasculpathy} OR {coronary artery atherosclerosis} OR {coronary artery constriction} OR { coronary artery obstruction} OR {cornary artery obstruction} OR {coronary artery thrombosis} OR {coronary subclavian steal syndrome} OR {heart infarction} OR {heart muscle ischemia} OR { ischemic cardiomyopathy} OR {kounis syndrome} OR {myocardial hibernation} OR {no reflow phenomenon} OR {silent myocardial ischemia} OR {takotsubo cadriomyopathy} OR {cardiovascular diseases} OR {cardiovascular disease} OR {cardiovascular abnormalities} OR {cardiovascular infections} OR {heart diseases} OR {vascular diseases} OR {coronary artery insufficiency} OR {coronary artery occlusive disease} OR {coronary heart disease}

{Sleep Apnea Syndrome} OR {obstructive sleep apnea} OR {obesity hypoventilation syndrome} OR {Upper Airway Resistance} OR {obstructive sleep apnea syndrome} OR {sleep apnea} OR {nocturnal apnea} OR {obstructive sleep apnea hypopnea syndrome} OR {obstructive sleep apnoea}

{hypertension} OR {high blood pressure} OR {high blood pressures} OR {hypertension malignant} OR { hypertension renal} OR {hypertensive retinopathy} OR {masked hypertension} OR {white coat hypertension} OR {acute hypertension} OR {arterial hypertension} OR {cardiovascular hypertension} OR {controlled hypertension} OR {endocrine hypertension} OR {high renin hypertension} OR {hypertensive disease} OR {hypertensive effect} OR { hypertensive response} OR {increased blood pressure} OR {neurogenic hypertension} OR {preexistent hypertension} OR {refractory hypertension} OR {salt high blood pressure} OR {salt hypertension} OR {secondary hypertension} OR {systemic hypertension}

{dyslipidemias} OR {dyslipidemia} OR {hyperlipidemias} OR {Hypolipoproteinemias} OR {Smith-Lemli-Opitz Syndrome} OR {dyslipoproteinemias} OR {dyslipoproteinemia} OR {dys lipidemia}

{stroke} OR {strokes} OR {cerebral stoke} OR {cerebral strokes} OR {brain vascular accident} OR {brain vascular accidents} OR {cerebrovascular apoplexy} OR {cerebrovascular stroke} OR {cerebralvascular strokes}OR {CVA} OR {CVAs} OR{apoplexy} OR {ceberovascular accident} OR {cerebrovascular accidents} OR {acute cerebrovascular accident} OR {acute cerebrovascular accidents} OR {brain infarction} OR {lacunar stroke} OR {acute cerebrovascular lesion} OR {acute focal cerebral vasculopathy} OR {apoplectic stroke} OR {apoplexia} OR {brain blood flow disturbance} OR {brain accident} OR {brain attack} OR {brain insult} OR {brain insults} OR {brain ischemic attack} OR {cerebral apoplexia} OR {cerebral insult} OR {cerebral vascular accident} OR {cerebral vascular insufficiency} OR {cerebro-vascular accident} OR {cerebrovascular arrest} OR {cerebrovascular failure} OR {cerebrovascular injury} OR {cerebrovascular insufficiency} OR {cerebrovascular insult} OR {cerebrovascular trauma} OR {cerebrum vascular accident} OR {ischaemic seizure} OR {ischemic cerebral attack} OR{ischemic seizure}


8

Limits

AND (LIMIT –TO (EXACTKEYWORD, “Human’) OR LIMIT-TO (EXACTKEYWORD, “Humans”) AND (LIMIT-TO (LANGUAGE,”English”)

Your query: (({non-insulin dependent diabetes mellitus} OR {diabetes mellitus type 2} OR {Ketosis Resistant Diabetes Mellitus} OR {Diabetes Mellitus Maturity Onset} OR ' {non-Insulin Dependent Diabetes Mellitus} OR {Type 2 Diabetes Mellitus} OR {Slow Onset Diabetes Mellitus} OR ' {table Diabetes Mellitus} OR {Diabetes Mellitus Type II} OR {MODY' OR 'NIDDM} OR {Adult Onset Diabetes Mellitus} OR {lipoatrophic diabetes mellitus} OR {type 2 diabetes} OR {type II diabetes} OR {dm 2} OR {insulin independent diabetes} OR {insulin independent diabetes mellitus} OR {non-insulin dependent diabetes}) OR ({ischemic heart disease} OR {ischaemic heart disease} OR {ischemic heart disease} OR {ischemic cardiac disease} OR {ischemia heart disease} OR {ischemic cardial disease} OR {ischemic cardiopathy} OR {acute coronary syndrome} OR {angina pectoris} OR {cardiac allograft vasculpathy} OR {coronary artery atherosclerosis} OR {coronary artery constriction} OR { coronary artery obstruction} OR {cornary artery obstruction} OR {coronary artery thrombosis} OR {coronary subclavian steal syndrome} OR {heart infarction} OR {heart muscle ischemia} OR { ischemic cardiomyopathy} OR {kounis syndrome} OR {myocardial hibernation} OR {no reflow phenomenon} OR {silent myocardial ischemia} OR {takotsubo cadriomyopathy} OR {cardiovascular diseases} OR {cardiovascular disease} OR {cardiovascular abnormalities} OR {cardiovascular infections} OR {heart diseases} OR {vascular diseases} OR {coronary artery insufficiency} OR {coronary artery occlusive disease} OR {coronary heart disease}) OR ({Sleep Apnea Syndrome} OR {obstructive sleep apnea} OR {obesity hypoventilation syndrome} OR {Upper Airway Resistance} OR {obstructive sleep apnea syndrome} OR {sleep apnea} OR {nocturnal apnea} OR {obstructive sleep apnea hypopnea syndrome} OR {obstructive sleep apnoea}) OR ({hypertension} OR {high blood pressure} OR {high blood pressures} OR {hypertension malignant} OR { hypertension renal} OR {hypertensive retinopathy} OR {masked hypertension} OR {white coat hypertension} OR {acute hypertension} OR {arterial hypertension} OR {cardiovascular hypertension} OR {controlled hypertension} OR {endocrine hypertension} OR {high renin hypertension} OR {hypertensive disease} OR {hypertensive effect} OR { hypertensive response} OR {increased blood pressure} OR {neurogenic hypertension} OR {preexistent hypertension} OR {refractory hypertension} OR {salt high blood pressure} OR {salt hypertension} OR {secondary hypertension} OR {systemic hypertension}) OR ({dyslipidemias} OR {dyslipidemia} OR {hyperlipidemias} OR {Hypolipoproteinemias} OR {Smith-Lemli-Opitz Syndrome} OR {dyslipoproteinemias} OR {dyslipoproteinemia} OR {dys lipidemia}) OR ({stroke} OR {strokes} OR {cerebral stoke} OR {cerebral strokes} OR {brain vascular accident} OR {brain vascular accidents} OR {cerebrovascular apoplexy} OR {cerebrovascular stroke} OR {cerebralvascular strokes} OR {CVA} OR {CVAs} OR {apoplexy} OR {ceberovascular accident} OR {cerebrovascular accidents} OR {acute cerebrovascular accident} OR {acute cerebrovascular accidents} OR {brain infarction} OR {lacunar stroke} OR {acute cerebrovascular lesion} OR {acute focal cerebral vasculopathy} OR {apoplectic stroke} OR {apoplexia} OR {brain blood flow disturbance} OR {brain accident} OR {brain attack} OR {brain insult} OR {brain insults} OR {brain ischemic attack} OR {cerebral apoplexia} OR {cerebral insult} OR {cerebral vascular accident} OR {cerebral vascular insufficiency} OR {cerebro-vascular accident} OR {cerebrovascular arrest} OR {cerebrovascular failure} OR {cerebrovascular injury} OR {cerebrovascular insufficiency} OR {cerebrovascular insult} OR {cerebrovascular trauma} OR {cerebrum vascular accident} OR {ischaemic seizure} OR {ischemic cerebral attack} OR {ischemic seizure})) AND (({Bariatric surgery} OR {bariatric operation} OR { bariatric operations} OR {bariatric procedure} OR {bariatric procedures} OR { bariatric surgical procedure} OR { bariatric surgical procedures} OR {obesity surgery} OR {sleeve gastrectomy} OR {gastric sleeve} OR {biliopancreatic bypass} OR {biliopancreatic diversion} OR {duodenal switch} OR {pancreatobiliary bypass} OR {gastric banding} OR {gastric banding} OR {stomach banding} OR {swedish gastric banding} OR {swedish adjustable gastric banding} OR {laparoscopic adjustable gastric banding} OR {laparoscopic adjustable silicone banding} OR {bariatric surgeries} OR {Gastric bypass} OR {roux-en-y gastric bypass} OR {greenville gastric bypass} OR {gastroileal bypass} OR {gastrojejunostomy} OR {gastrojejunostomies} OR {gastroplasty} OR {gastroplasties} OR {collis gastroplasty} OR {vertical-banded gastroplasty} OR {vertical banded gastroplasty} OR {vertical banded gastroplasties} OR {jejunoileal bypass} OR {jejuno ileal bypass} OR {ileojejunal bypass} OR {ileojejunal bypasses} OR {intestinal bypass} OR {intestinal bypasses} OR {lipectomy} OR {lipectomies} OR {aspiration lipectomy} OR {aspiration lipolysis} OR {suction lipectomy} OR {suction lipectomies} OR {suction lipolysis}


9

OR {liposuction} OR {liposuctions} OR {lipoplasty} OR {lipoplasties}) AND ({body mass} OR {body mass} OR {Body Mass Index} OR {Quetelet Index} OR {Quetelets Index} OR {BMI} OR {body ban mass})) AND (LIMIT-TO(PUBYEAR, 2010) OR LIMIT-TO(PUBYEAR, 2009) OR LIMIT-TO(PUBYEAR, 2008) OR LIMIT-TO(PUBYEAR, 2007) OR LIMIT-TO(PUBYEAR, 2006) OR LIMIT-TO(PUBYEAR, 2005) OR LIMIT-TO(PUBYEAR, 2004) OR LIMIT-TO(PUBYEAR, 2003)) AND (LIMIT-TO(LANGUAGE, "English"))

COCHRANE

“Bariatric surgery” OR “bariatric surgery” OR “bariatric surgeries” OR “Gastric bypass” OR “roux-en-y gastric bypass” OR “greenville gastric bypass” OR “gastroileal bypass” OR “gastrojejunostomy” OR “gastrojejunostomies” OR “gastroplasty” OR “gastroplasties” OR “collis gastroplasty” OR “vertical-banded gastroplasty” OR “vertical banded gastroplasty” OR “vertical-banded gastroplas” OR “Jejunoileal bypass” OR “jejunoileal bypass” OR “jejunoileal bypass” OR “jejuno-ileal bypasses” OR “ileojejunal bypass” OR “ileojejunal bypasses” OR “intestinal bypass” OR “intestinal bypasses” OR “lipectomy”[Mesh] OR “lipectomies” OR “aspiration lipectomy” OR “aspiration lipolysis” OR “suction lipectomy” OR “suction lipectomies” OR “ suction lipolysis” OR “liposuction” OR “liposuctions” OR “lipoplasty” OR “lipoplasties” OR “biliopancreatic bypass” OR “biliopancreatic diversion” OR “ duodenal switch” OR “pancreatobiliary bypass” OR “gastric banding” OR “ Stomach banding” OR “swedish gastric banding” OR “swedish adjustable gastric banding” OR “ laparoscopic adjustable gastric banding” OR “laparoscopic adjustable silicone banding” OR “bariatric operation” OR “ bariatric operations” OR “ bariatric procedure” OR “ bariatric procedures” OR “bariatric surgical procedure” OR “ bariatric surgical procedures” OR “obesity surgery” Or “sleeve gastrectomy” OR “gastric sleeve”

"Body Mass Index" OR "Body Mass Index" OR “Quetelet Index” OR “Quetelets Index” OR “BMI” OR “body ban mass”

“diabetes mellitus type 2” OR “Ketosis-Resistant Diabetes Mellitus” OR “Diabetes Mellitus Maturity-Onset” OR “Diabetes Mellitus Maturity Onset” OR “Non-Insulin-Dependent Diabetes Mellitus” OR “Type 2 Diabetes Mellitus” OR “Slow-Onset Diabetes Mellitus” OR “Stable Diabetes Mellitus” OR “Diabetes Mellitus Type II” OR “MODY” OR “NIDDM” OR “Adult-Onset Diabetes Mellitus” OR “lipoatrophic diabetes mellitus” OR “type 2 diabetes” OR “type II diabetes” OR “dm 2” OR “insulin independent diabetes” OR “insulin independent diabetes mellitus” OR “ketosis resistant diabetes mellitus” OR “non insulin dependent diabetes” OR “non insulin dependent diabetes mellitus” OR “type 2 diabetes mellitus ”

“cardiovascular diseases” OR “cardiovascular disease” OR “cardiovascular abnormalities” OR “cardiovascular infections” OR “Heart diseases” OR “vascular diseases” OR “coronary artery insufficiency” OR “coronary artery occlusive disease” OR “coronary heart disease” OR “coronary insufficiency” OR “coronary occlusive disease” OR “ischemic heart disease” OR “ischaemic heart disease” OR “ ischemic heart disease” OR “ischemic cardiac disease” OR “ ischemic cardial disease” OR “ ischemic cardiopathy”

“sleep apnea obstructive” OR “obstructive sleep apnea” OR “obesity hypoventilation syndrome” OR “Upper Airway Resistance Sleep Apnea Syndrome” OR “obstructive sleep apnea syndrome” OR “sleep apnea” OR “nocturnal apnea” OR “obstructive sleep apnea hypopnea syndrome” OR “obstructive sleep apnoea”

“hypertension” OR “high blood pressure” OR “high blood pressures” OR “hypertension malignant” OR “ hypertension renal” OR “hypertensive retinopathy” OR “masked hypertension” OR “white coat hypertension” OR “acute hypertension” OR “ arterial hypertension” OR “cardiovascular hypertension” OR “controlled hypertension” OR “endocrine hypertension” OR “high renin hypertension” OR “hypertensive disease” OR “hypertensive effect” OR ” hypertensive response” OR “ increased blood pressure” OR “neurogenic hypertension” OR ”preexistent hypertension” OR” refractory hypertension” OR “salt high blood pressure” OR “salt hypertension” OR “secondary hypertension” OR “systemic hypertension”

“dyslipidemias” OR “dyslipidemia” OR “hyperlipidemias” OR “Hypolipoproteinemias” OR ”Smith-Lemli-Opitz Syndrome” OR “dyslipoproteinemias” OR “dyslipoproteinemia” OR “dys lipidemia”

“stroke” OR “strokes” OR “cerebral stoke” OR “cerebral strokes” OR “brain vascular accident” OR “brain vascular accidents” OR “cerebrovascular apoplexy” OR “cerebrovascular stroke” OR “cerebralvascular strokes” OR “CVA” OR “CVAs” OR “apoplexy” OR “ ceberovascular accident” OR “ cerebrovascular accidents” OR “acute cerebrovascular


10

accident” OR “acute cerebrovascular accidents” OR “brain infarction” OR “lacunar stroke” OR “acute cerebrovascular lesion” OR “acute focal cerebral vasculopathy” OR “apoplectic stroke” OR “apoplexia” OR “brain blood flow disturbance” OR “brain accident” OR “ brain attack” OR “brain insult” OR “brain insults” OR “brain ischemic attack” OR “cerebral apoplexia” OR “cerebral insult” OR “cerebral vascular accident” OR “cerebral vascular insufficiency” OR “cerebro vascular accident” OR “cerebrovascular arrest” OR “cerebrovascular failure” OR “cerebrovascular injury” OR “cerebrovascular insufficiency” OR “cerebrovascular insult” OR “cerebrovascular trauma” OR “cerebrum vascular accident” OR “ischaemic seizure” OR “ischemic cerebral attack” OR “ ischemic seizure”

Clinicaltrials.gov

Search terms

Bariatric surgery and body mass index and diabetes

Bariatric surgery and body mass index and cardiovascular disease

Bariatric surgery and body mass index and hypertension

Bariatric surgery and body mass index and dyslipidemia

Bariatric surgery and body mass index and stroke

Bariatric surgery and body mass index and sleep apnea

Bariatric surgery and body mass index and quality of life


2. Models used to estimate operative mortality and complication rates and remission rate of theobesity-attributable comorbidities

2.1 Meta-analytic approach proposed by Bhaumik et al. (Bhaumik models)

Denote as the observed percentage of interest. Let be the number of studies included in the meta-analysis, ,1,⋯ , , is the sample size for study . Bhaumik et al.1 proposed a meta-analytic method that eliminates much of the bias from moment-based estimators of combined treatment effects in rare binary event cases. The estimator is a simple (unweighted) average:

1

,

For the variance estimate, we slightly modified the variance estimate proposed by Bhaumik et al. to account for the different study conditions of our study as follows:

1 1 1

,

where is the estimated heterogeneity parameter and can be obtained from the solution of the following equation:

1 0,

where , in which , and

∑ ∑

.

2.2 Bayesian random-effects models

is denoted as the number of patients of interest. Assume ~ , . Let

exp1 exp

,

and

log1

For the priors, we use

~ , ,

~ 10, 10 , and

~ 0, 2 .2,3

(1)


3. Mixed treatment comparison meta-analysis

3.1 Network of evidence

Using mixed treatment comparison (MTC) meta-analysis,4 we estimated relative surgical effects on change in body mass index (BMI) from networks of evidence – randomized controlled trials (RCTs) comparing different surgical procedures in terms of post-surgery BMI change. eFigure 1 demonstrates the network of evidence across 17 studies included in the MTC meta-analysis. Each line presents one or two RCTs as indicated by the thickness of the line. The number at the end of each line corresponds to a type of bariatric surgery, which is detailed in eTable 3. Among these procedures, the laparoscopic Roux-en-Y Gastric Bypass (LRYGB) was most commonly compared with, having head-to-head comparisons against 6 other surgical procedures. Therefore, it was placed at the center of the network, and was treated as the reference surgery in the MTC meta-analysis.

3.2 MTC meta-analysis models

Let , , denote the observed mean BMI change (∆BMI) at timepoint in arm of study , which was assumed to have a

normal distribution with mean , , and variance , , .

, , ~ , , , , ,

Model 1:

, , , ,

where , is the mean BMI change at timepoint in the baseline arm (arm 1) of study , and , is the difference in mean

BMI change between arm and arm 1 for study ( , 0).

The pooled surgery effects, for surgery , relative to the reference surgery, LRYGB ( 1), are the parameters of interest. The surgery effects in arm of study , , , are assumed to be drawn from a common distribution with mean

, ,and (between study) standard deviation :

, ~ , ,, ,

where , denotes the surgical procedure used in arm of study . is assumed to be constant across surgery comparisons

(homogeneous).

We estimated the model using Bayesian technique. , and were given non-informative Gaussian priors,

0, 10,000 , while was assigned a wide uniform prior, 0, 20 .

Model 2: Model 2 is identical to Model 1, except that surgery effects were assumed to be constant within each surgery category.

,

where is the pooled mean surgery effect for surgery category relative to the first category, gastric bypass (GB), and ~ 0, 10,000 .

We estimated all mean category effects relative to GB.

Model 3: Model 3 is similar to Model 2, except that the surgery effects are exchangeable within categories, i.e., the surgery effects for different surgical procedures in the same category are similar. The surgery effects within the same category were


assumed to be drawn from a normal distribution with category mean and variance . We assumed were different across categories, but was the same.

~ , for categories including more than one surgical procedure

for categories including only one type of surgery

~ 0, 10,000 and ~ 0, 20

We estimated mean surgery effects relative to LRYGB.

Model 4:

, , , , , .

In model 4, we incorporated time factors and estimated surgery effects separately for three terms: short (<1 year), mid (≥1 and <3 years), and long term (≥3 years). This allows relative surgery effects to vary over time, while assuming the effects are piecewise constant within each time intervals. , , , are assumed to be drawn from a common distribution with mean

, , , , , , and (between study) standard deviation :

, ~ , , , , , ,, ,

where denotes the time interval, and , ~ 0, 10,000 .

We estimated mean surgery effects relative to LRYGB for each time interval.

4. Estimation results

4.1 Bayesian and Bhaumik random-effects meta-analyses of surgical risks and benefits (Bayesian and Bhaumik)

We present the full set of estimation results in eTable 1, in which part of the Bayesian results are presented in Table 2.

4.2 Random-effects and fixed-effect meta-analyses using the Frequentist technique (FRE and FFE)

We present in eTable 2 the estimation results and I2 index, measuring the percentage of variation across studies that is due to heterogeneity rather than random chance.5,6 Part of the FRE results are presented in Table 3. Publication bias was evaluated using funnel plots and Egger’s test.7,8 eFigure 2 shows the funnel plots and Egger’s test results for the outcomes of yearly BMI change for which publication bias was able to be evaluated. The Egger’s test for small-study effect showed that there was no evidence showing small study effects for all post-surgery yearly BMI change outcomes, except for post-surgery years 1 and 3 BMI change for observational studies.

4.3 Meta-regression analyses of BMI change

We conducted meta-regression analyses for post-surgery year 1-2 BMI change. We adjusted for characteristics of patients (pre-surgery mean BMI, percentage of female patients, and age at surgery), study design (RCTs or not) and quality, surgery category (GB, AGB, VBG, SG, Control, or Combined), and geographic location where surgery was performed (North America, Europe, Asia, or others). For study quality, we created nine dummy variables (QC1-9). QC1: surgeries are clearly defined; QC2: clear time points were given for outcomes; QC3: adjustment for potential confounders in analysis in observational studies (OBSs); QC4: adequate randomization for RCTs; QC5: a priori sample size calculations were defined; QC6: loss to follow up information was given, but loss to follow up was >20%; QC7: loss to follow up information was given, and loss to follow up <20%; QC8: funding and conflicts of interest were declared, but the study was funded by


surgery-related industry; and QC9: funding and conflicts of interest were declared, and there was no link to industry. Analyses for post-surgery year 3-5 BMI change were not included due to insufficient observations. The results are shown in eTable 4.

Analyses for the first 2-year post-surgery BMI change included 91 and 48 observations. Older patients were associated with less BMI loss for both years (p = 0.00 and 0.01). Percentage of females was not statistically significant throughout year 1 to year 2 (p = 0.26 and 0.71). Pre-surgery BMI was a strong predictor for post-surgery BMI for both years (p = 0.00 and 0.01). RCT design was associated with more weight loss, but was not statistically significant in the second year (p = 0.00 for the first year and p = 0.4 for the second year). Whether an RCT had adequate randomization and whether a study provided a priori information on sample size calculation were positively associated with the first year BMI change (p = 0.00 and 0.001). Loss to follow up >20% was significantly associated with more weight loss in the second year (p = 0.02), but not in the first year (p = 0.65). In the first year after surgery, AGB (p = 0.00), SG (p = 0.02), VBG (p = 0.01), and non-surgical interventions (p = 0.00) were less effective on BMI loss than GB. But the difference was not found in the second year. Geographical locations where surgery was performed were not statistically significant in any years.

4.4 MTC meta-analysis of BMI change for RCTs

eTable 5 shows the MTC estimates of the parameters ( , 2,⋯ ,11) in Model 1 and corresponds to Figure 2 in the text. The estimated pooled surgery effects (Column 2) were compared to the effect of LRYGB (see eTable 3). Positive values represent that LRYGB outperformed the target surgical procedure. Therefore, LRYGB with presurgery weight loss, laparoscopic biliopancreatic diversion with duodenal switch, and biliopancreatic diversion with RYGB (procedure #3, 4, and 5) had greater effects on BMI loss than LRYGB. Non-surgical interventions did the worst in terms of BMI loss. On average,the effect of non-surgical interventions on BMI loss was approximately 14 kg/m2 less than that of LRYGB. Procedures in AGB category (either using LAP-BAND or Swedish band) were outperformed by LRYGB by 9-10 kg/m2. All other relative effects can be obtained from these basic estimates via the consistency equations based on the exchangeability assumptions.9,10 For example, the estimated relative effect of surgical procedure #2 to #3 is 3.34 kg/m2 because 1.62-(-1.72) = 3.34; in other words, LRYGB with pre-surgery weight loss helped patients lose 3.34 kg/m2 more on average compared to ORYGB.

eTable 6 shows the MTC estimates corresponding to the parameters in Model 2. The results are also shown in Figure 2. The estimated pooled mean category effects (Column 2) were compared to the effect of the first category of surgery, GB (see eTable 3). The results show that sleeve gastrectomy (SG) was comparable to GB – overall, BMI loss was only 0.27 kg/m2 less than GB. Vertical banded gastroplasty (VBG) was less effective than GB in terms of BMI change (by 3.4 kg/m2), but more effective than AGB (by 5.4 kg/m2). Model 2 makes a strong assumption that surgery effects were constant within categories, but it is informative when comparing different categories of bariatric surgery.

eTable 7 shows the MTC estimates corresponding to the parameters in Model 3. The estimated pooled surgery and category effects (Column 2) were compared to that of LRYGB (see eTable 3). Model 3 makes a strong assumption that the between surgery within category standard deviation, , is the same across all categories. In addition, this model assumes surgical procedures in the same category are drawn from the same distribution (exchangeability of surgery effects within categories). Its results would prone to bias if the common variance assumption and the exchangeability assumption were not valid for all categories.

MTC estimates corresponding to the parameters in Model 4 are presented in eTable 8. The estimated pooled surgery effects within the designated time interval were compared to the effect of the first type of surgery, LRYGB (see eTable 3). Surgery #3-5 and 9 had better BMI loss effect than LRYGB the first year after surgery; surgery #4, 5, and 10 had better performance in terms of BMI loss than LRYGB between 1 and 3 years after surgery. Surgery #9 and 10 performed better than LRYGB >3 years after surgery.


15

MTC estimates corresponding to the parameters in Model 4 are presented in eTable 8. The estimated pooled surgery effects within the designated time interval were compared to the effect of the first type of surgery, LRYGB (see eTable 3). Surgery #3-5 and 9 had better BMI loss effect than LRYGB the first year after surgery; surgery #4, 5, and 10 had better performance in terms of BMI loss than LRYGB between 1 and 3 years after surgery. Surgery #9 and 10 performed better than LRYGB >3 years after surgery.


16

5. References

1. Bhaumik DK, Amatya A, Normand SL, et al. Meta‐Analysis of Rare Binary Adverse Event Data. Journal ofthe American Statistical Association. 2012;107(498):555‐567.

2. Smith TC, Spiegelhalter DJ, Thomas A. Bayesian approaches to random‐effects meta‐analysis: acomparative study. Stat Med. Dec 30 1995;14(24):2685‐2699.

3. Warn DE, Thompson SG, Spiegelhalter DJ. Bayesian random effects meta‐analysis of trials with binaryoutcomes: methods for the absolute risk difference and relative risk scales. Stat Med. Jun 152002;21(11):1601‐1623.

4. Dakin HA, Welton NJ, Ades AE, Collins S, Orme M, Kelly S. Mixed treatment comparison of repeatedmeasurements of a continuous endpoint: an example using topical treatments for primary open‐angleglaucoma and ocular hypertension. Stat Med. Jul 5 2011.

5. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. Jun 152002;21(11):1539‐1558.

6. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. Bmj. Sep 62003;327(7414):557‐560.

7. Light RJ, Pillemer DB. Summing up : the science of reviewing research. Cambridge, Mass.: HarvardUniversity Press; 1984.

8. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta‐analysis detected by a simple, graphicaltest. Bmj. Sep 13 1997;315(7109):629‐634.

9. Lu G, Ades A. Modeling between‐trial variance structure in mixed treatment comparisons. Biostatistics.Oct 2009;10(4):792‐805.

10. Lu G, Ades AE. Assessing Evidence Inconsistency in Mixed Treatment Comparisons. Journal of theAmerican Statistical Association. June 2006;101 474:447‐459.

eFigure 1 Network diagram


17

Egger's test for small-study effects: p = 0.996 Egger's test for small-study effects: p = 0.784




18

Egger's test for small-study effects: p = 0.621

Publication bias was evaluated for yearly BMI change outcomes of all surgical procedures for which at least two study arms were included. RCT: randomized controlled trials; OBS: observational studies; s.e.: standard error.

eFigure 2 Funnel plots with pseudo 95% confidence limits and Egger’s test results


19

eTable 1 Definitions of comorbid conditions and comorbidity improvement

Study No.

Authors Proce-dure

RCT

No. of patients with the comorbid condition

No. of patients with improve-ment

Definition of the comorbid condition

Definition of improvement

Diabetes

100015

Herrera MF, Pantoja JP, Velazquez-Fernandez D, Cabiedes J, Aguilar-Salinas C, Garcia-Garcia E, et al

GB Y 4 4

"An oral glucose tolerance test using a dose of 75 g of glucose after an overnight fasting (12 h) period was performed in all patients....Diabetes was diagnosed when glucose was ≥200 mg/dl 2 h postload."

Not Available

GB Y 6 5

100037

Lee WJ, Ser KH, Chong K, Lee YC, Chen SC, Tsou JJ, et al.

SG N 20 10

Diabetes was diagnosed in "patients aged 30--60 years who had a history of T2DM for 6 months [and] poorly controlled (HbA1C 7.5%)….The patients had to have their C-peptide above 1 ng/mL without irreversible major organ damage related to diabetes."

“Remission of T2DM was defined as fasting glucose levels less than 126 mg/dL in addition to a HbA1c value less than 6.5% without the use of oral hypoglycemics or insulin.”

100072 Chao SH. AGB N 2 1 Not Available Not Available

100129

Toouli J, Kow L, Ramos AC, Aigner F, Pattyn P, Galvao-Neto MP, et al.

AGB N 11 11 Not Available

"Changes in co-morbidities were assessed by each investigator by comparing the following categorical and noncategorical parameters to their preoperative status: (1) changes in therapy/medication (i.e., increased, decreased, discontinued, no change, could not assess); and/or (2) changes in diagnostic parameters (laboratory or test results) recorded in the medical records during follow-up and at the one-time prospective study visit. Using this combination of parameters, the investigators


20

Study No.

Authors Proce-dure

RCT





provided their assessment of changes in disease severity (e.g., no change, improved, worsened or could not assess); and current disease status (e.g., controlled, not controlled, resolved, or could not assess)."

100144 Sultan S, Parikh M, Youn H, Kurian M, Fielding G, Ren C.

AGB N 15 15

"The presence of comorbidities was defined by either the requirement for physician-prescribed medications…or such a diagnosis by the patient’s primary care physician."

"For the purposes of this study, ‘‘resolution’’ of a comorbidity was defined as the discontinuation of physician-prescribed medications postoperatively, and ‘‘improvement’’ was defined as a decreased dosage of physician-prescribed medications."

100165 Iannelli A, Anty R, Piche T, Dahman M, Gual P, Tran A, et al.

GB N 13 11Not Available Not Available

GB N 6 6

100264

Pinheiro JS, Schiavon CA, Pereira PB, Correa JL, Noujaim P, Cohen R.

GB Y 55 54"T2DM was diagnosed if thepatient presented with 2 fasting serum glucose results of 120 mg/dL and hemoglobin A1c (HbA1c) 7.5%."

"The co-morbidities were considered controlled if the patients required no medication and had normal blood test results during follow-up. The co-morbidities were considered improved if patients required less medication or had improved blood test results compared with before surgery."

GB Y 45 43

100296

Busetto L, Angrisani L, Basso N, Favretti F, Furbetta F, Lorenzo M, et al.

GB N 289 279"At baseline, being diabetic wasdefined as having a fasting plasma glucose level ≥7.0 mmol/l or being under the use of any antidiabetic drug..."

"...An improvement in the diabetic condition during follow-up was based upon a normalization of glucose levels or a reduction of antidiabetic medications."

GB N 46 46


21

Study No.

Authors Proce-dure

RCT





100297

Dixon JB, O'Brien PE, Playfair J, Chapman L, Schachter LM, Skinner S, et al.

AGB Y 30 22

Diabetes was diagnosed when patients had been "...diagnosed with clearly documented type 2 diabetes within the previous 2 years…"

"The primary end points of the study related to glycemic control at 2 years after randomization. These were assessed as the proportion of participants achieving remission (exceptional glycemic control) of type 2 diabetes, defined as fasting plasma glucose levels less than 126 mg/dL…in addition to HbA1c values less than 6.2% without the use of oral hypoglycemics or insulin… Our protocol recommended cessation of metformin, if prescribed, when the fasting insulin concentration was normal (17.0 uIU/mL) and the HbA1c value was less than 6.2% with a normal fasting plasma glucose level less than 108.0 mg/dL."

Con-trol

Y 30 4

100349

Whitson BA, Leslie DB, Kellogg TA, Maddaus MA, Buchwald H, Billington CJ, et al.

GB N 5 5

"All five of the diabetic patients were on medication preoperatively to control their hyperglycemia. Four of the five patients were on oral agents and one patient was on short- and long-acting insulin."

"Postoperatively, all of the patients were off oral medications with 80% (four of five patients) of the diabetic cohort demonstrating resolution of their diabetes. One patient in the diabetic cohort continued on insulin postoperatively, at a lower dose."

100353 Bessler M, Daud A,Kim T, DiGiorgi M.

Com-bined

Y 12 11Not available Not available

GB Y 11 11

100385 Angrisani L, LorenzoM, Borrelli V.

GB Y 1 1 Not available Not available

100405 Taylor CJ, Layani L. AGB N 15 12 Not available "...Patients were… asked to participate in a detailed


22

Study No.

Authors Proce-dure

RCT





postoperative questionnaire package [with a] purpose-designed co-morbidity and medication survey, seeking information concerning change in 11 common obesity-related co-morbidities and medication requirements…Patients were asked to indicate which of 5 options (much worse /worse /same/ better /much better) most accurately described changes in these co-morbidities...Changes in medication requirements were also sought (stopped taking/use less/use same/ use more/started taking).”

100425

Nelson WK, Fatima J, Houghton SG, Thompson GB, Kendrick ML, Mai JL, et al.

GB N 118 111 Not available Not available

100452

Nelson LG, Lopez PP, Haines K, Stefan B, Martin T, Gonzalez R, et al.

GB N 11 11 Not available

"Improvement in hypertension [and] diabetes… was determined by subjective symptomatic relief and assessment of the reduction or cessation of medication use."

100460

Skroubis G, Anesidis S, Kehagias I, Mead N, Vagenas K, Kalfarentzos F.

GB Y 10 7

Not available

"Seven of the 10 RYGBP patients suffering from diabetes type 2 preoperatively were cured…[and]… diabetes type 2 completely resolved in all BPD patients, including the one who had been on insulin preoperatively."

GB Y 7 7


23

Study No.

Authors Proce-dure

RCT





100466

Puzziferri N, Austrheim-Smith IT, Wolfe BM, Wilson SE, Nguyen NT.

GB Y 5 5

Not available

"Changes in comorbidities were analyzed according to the following scale…A designation of improved was assigned if the patient experienced decreased severity or frequency of symptoms or decreased dosage or number of medications. A designation of resolved was assigned if the patient had resolution of symptoms and did not require medication for treatment."

GB Y 8 7

100471

Kim TH, Daud A, Ude AO, DiGiorgi M, Olivero-Rivera L, Schrope B, et al.

GB N 45 32

Not available

"Significant improvement was defined as less frequent symptoms or controlled with less medication, whereas resolution was defined as normal lab values, resolution of symptoms, or no medication."

AGB N 33 25

100493

van Dielen FM, Soeters PB, de Brauw LM, Greve JW.

VBG Y 7 6 "Co-morbidities were recorded when patients were medically treated for the disorder. "

"…At 1 year postoperatively, 83% of patients who had been treated for this co-morbidity no longer required medication."

AGB Y 5 4

100539

Silecchia G, Greco F, Bacci V, Boru C, Pecchia A, Casella G, et al.

AGB N 8 5Not available Not available

AGB N 5 3

100596

Kalfarentzos F, Papadoulas S, Skroubis G, Kehagias I, Loukidi A, Mead N.

GB N 23 23

"There were 23 patients with diabetes (blood glucose 125 mg/dl) preoperatively. Of these patients, 18 were not on any type of medication either because they were unaware of the problem or because they were on conservative management with diet alone.

"Post operatively, blood glucose levels had returned to normal in all patients by the first postoperative month and by the third month all 5 patients on oral hypoglycemic agents were able to discontinue treatment."


24

Study No.

Authors Proce-dure

RCT





Five patients were being treated with oral hypoglycemic agents (for a period of 5 years) and none were insulin dependent."

200003

Pajecki D, Mancini MC, Halpern A, Zilberstein B, Garrido AB,Jr, Cecconello I.

AGB N 4 3 Not available

Of the three patients whose diabetes improved, "one stopped taking any medication and [had] normalized HbA1c, [and] two had significant reduction in HbA1c and the amount of medication required”.

200025 Matlach J, Adolf D, Benedix F, Wolff S.


"Resolution of comorbidity was considered when medical treatment was no longer needed. Improvement of comorbidity was determined as reduced dose or combination of medications."

200041

Boza C, Gamboa C, Perez G, Crovari F, Escalona A, Pimentel F, et al.

AGB N 11 3 Not available Not available

200043

Kasza J, Brody F, Vaziri K, Scheffey C, McMullan S, Wallace B, et al.


"...Partial resolution [meant] either dose reduction of medication or self-reported improvement in symptoms."

300026

Nienhuijs SW, De Zoete JP, Berende CA, De Hingh IH, Smulders JF.

SG N 20 18"The co-morbidity was defined as a condition for which medical treatment was prescribed."

Post-operatively 8 patients required lower doses of treatment and 10 patients stopped treatment after 6 months.

300043

Sakcak I, Avsar MF, Erdem NZ, Hamamci EO, Bostanoglu S, Sonisik M, et al.


"Insulin treatment was no longer necessary in one patient and anti-diabetic treatment was no longer necessary in 6 patients during the post-operative period."

300052 Batsis JA, Lopez- GB N 50 30 "Diabetes was defined as use of "Improvement in co-morbidity


25

Study No.

Authors Proce-dure

RCT





Jimenez F, Collazo-Clavell ML, Clark MM, Somers VK, Sarr MG.

oral medications or insulin, fasting glucose 126 mg/dL, or HbA1c 6.5%."

was defined as patients with a baseline diagnosis no longer meeting follow-up diagnostic criteria."

300071

Torchia F, Mancuso V, Civitelli S, Di Maro A, Cariello P, Rosano PT, et al.

AGB N 11 10Diabetes was diagnosed when fasting glycemia >120–130 mg/dl and HbA1c >9%.

Improvement in diabetic condition meant having fasting glycemia <110 mg/dl and HbA1c <6% “without pharmacological support".

300133 Parikh M, Duncombe J, Fielding GA.

AGB N 8 8

"All patients were fully assessed for comorbidities…on the basis of the history, physical examination findings, and blood test results."

"None [of the patients] needed medication" after the procedure.

300135

Silecchia G, Boru C, Pecchia A, Rizzello M, Casella G, Leonetti F, et al.

SG N 17 16 Not available Not available

300170 He M, Stubbs R. GB N 52 52"Diabetes was determined by history or preoperative oral glucose tolerance test."

"Changes in comorbidities were classified as follows: · Resolution—normalisation of the comorbidities without requirement for medication. · Improvement—better control of the comorbidities with the same or reduced medication requirement. · No change—no evidence of resolution or improvement."

400030 Pournaras DJ, Osborne A, Hawkins SC, et al.

GB N 22 16Not available

"In our study, we defined remission of type 2 diabetes when all the following criteria were met: 1. Fasting plasma glucose below 7 mmol/L in the absence of medical treatment for at least 3 days. 2. A 2-hour plasma glucose below 11.1 AGB N 12 2


26

Study No.

Authors Proce-dure

RCT





mmol/L following an oral glucose tolerance test (OGTT) as specified by the World Health Organisation. 3. Glycated haemoglobin (HbA1c) below 6% after 3 months of last hypoglycemic agent usage."

400034

Schouten R, Wiryasaputra DC, Van Dielen FM, Van Gemert WG, Greve JW.

AGB N 5 0

Not available Not available VBG N 7 7

400048

Basso N, Casella G, Rizzello M, Abbatini F, Soricelli E, Alessandri G, et al.

SG N 20 17Not available Not available

SG N 44 44

400049 Behrens C, Tang BQ,Amson BJ.

SG N 19 19 Not available

"Resolution was defined as normalization of the metrics defining each pathology without use of medication. Improvement was defined as either improved control of said metrics while on the same dose of medication or continued adequate control of metrics while on a reduced amount of medication."

400050

Bobowicz M, Lehmann A, Orlowski M, Lech P, Michalik M.


400057 Clough A, Layani L, Shah A, Wheatley L, Taylor C.

AGB N 35 26 Not available Improvement was defined by "self-reported improvements or deteriorations."

400060 Depaula AL, Stival AR, Halpern A, Vencio S.

SG N 19 16

"All patients with associated T2DM were using antidiabetic medication (oral hypoglycemic agents, insulin, or both) for a

Not available


27

Study No.

Authors Proce-dure

RCT





minimum of 1 year, had at least 3 years of diagnosis, and were diagnosed according to the American Diabetes Association criteria (ADA)."

400066

Fezzi M, Kolotkin RL, Nedelcu M, Jaussent A, Schaub R, Chauvet MA, et al.

SG N 12 9

"Twelve patients (16.9%) had a type II diabetes treated by oral antidiabetics (11 patients) or insulin (one patient)."

"After 12 months, nine patients (75%) stopped or reduced their treatment…”

400068 Hayes MT, Hunt L A, Foo J, Tychinskaya Y, Stubbs RS

GB N 107 107

"The diagnosis of T2DM was established in two ways. In the first, patients had clear prior documentation of the diagnosis and/or were receiving treatment for T2DM. In the second, the diagnosis was established by oral glucose tolerance test which was routinely performed in those without a known history of diabetes. In this context a fasting glucose≥7.0 mmol/L and/or a 2 h glucose≥ 11.1 mmol/L led to the patient being designated as having previously unrecognized diabetes."

Patients were classified into the following three groups. “Resolution: fasting plasma glucose <6.0 mmol/L and HbA1c<6.0% without requirement for medication, Indeterminate: fasting plasma glucose is ≥6 but ≤ 7 mmol/L and/or HbA1c ≥6 but ≤7% without requirement for medication, Unresolved: fasting plasma glucose >7.0 mmol/L and/or HbA1c>7.0%, or requirement for antidiabetic medication…Patients classified as indeterminate were included in the resolved group because with their level of fasting plasma glucose and HbA1c, without the need for medication, a secure diagnosis of diabetes could not be made"

GB N 20 0

400069 Higa K, Ho T, Tercero F, Yunus T, Boone KB.

GB N 45 37

Initial diagnosis was classified in the following way: Mild: "Diet controlled"; Moderate: "Controlled with oral medications"; Severe: "Requires insulin"

Not available


28

Study No.

Authors Proce-dure

RCT





400072

Hutter MM, Schirmer BD, Jones DB, Ko CY, Cohen ME, Merkow RP, et al.

SG N 249 137

Not available Not available AGB N 2258 994GB N 4452 3695GB N 380 255

400075

Kalfarentzos F, Skroubis G, Karamanakos S, Argentou M, Mead N, Kehagias I, et al.

GB N 15 15

Not available Not available GB N 12 12

GB N 182 181

400079 Lee WJ, Chen CY, Chong K, Lee YC, Chen SC, Lee SD.

GB N 16 13

"All patients had severe T2DM and 6 required insulin."

"The patients were followed up and assessed for their T2DM status 2 years postoperatively. A fasting glucose level 110 mg/dL and HbA1c 6.0% without the use of oral hypoglycemic agents or insulin was defined as complete remission. A fasting glucose level 126 mg/dL and HbA1c 6.5% was considered partial remission."

SG N 16 3

400100

Scopinaro N, Adami GF, Papadia FS, Camerini G, Carlini F, et al.

GB N 15 10Diabetic status was determined by having been "...diabetic for ≥3 years [and when] HbA1c ≥7.5% despite medical therapy…"

"Diabetes was considered remitted when serum glucose values were ≤125 mg/dL and HbA1c ≤6.0%, on free diet and with no antidiabetic medical therapy, controlled when, under the same conditions, HbA1c was ≤7.0%, and improved when preoperative HbA1c was steadily reduced by at least 1% with less antidiabetic therapy."

Con-trol

N 15 15

400105 Tayyem R, ObondoC, Ali A

AGB N 10 8 Not available Not available

400106 Tinoco A, El-Kadre L, Aquiar L, Tinoco R, Savassi-Rocha P.

SG N 30 24

Diabetic status was determined by the following criteria: "(1) patients diagnosed with T2DM for at least 3 years according to

Diabetes improvement was defined by "...(1) those in remission of T2DM, defined by HbA1c\6.5% without oral


29

Study No.

Authors Proce-dure

RCT





the standards adopted by the American Diabetes Association (ADA) [24]—i.e., fasting glucose C126 mg/dl, glycosylated hemoglobin (HbA1c) C6.5%, fasting plasma glucose C200 mg/dl, and 2-h glucose C200 mg/dl in the 75-g oral glucose tolerance test; (2) evidence of stable treatment with oral hypoglycemic drugs and/or insulin for more than 12 months."

hypoglycemic drugs or insulin; and (2) those with alleviation of their T2DM, defined as a reduction of at least 25% in the fasting plasma glucose level and of at least 1% in the HbA1c level with hypoglycemic drug treatment."

400114 Boza C, Salinas J, Salgado N, et al.


400116 Chopra A, Chao E, Etkin Y, Merklinger L, Lieb J, Delany H.


"Resolution of diabetes mellitus (DM) was defined as cessation of anti-diabetes medications by the primary care physician or by an HbA1c level of<7%."

400126 Mukherjee S, Devalia K, Rahman MG, Mannur KR.


"At the end of 1 year of follow-up, 18 diabetic patients (90%) no longer required their diabetic medications..."

Hypertension

100015

Herrera MF, Pantoja JP, Velazquez-Fernandez D, Cabiedes J, Aguilar-Salinas C, Garcia-Garcia E, et al.

GB Y 8 6

Not Available Not Available

GB Y 8 7


100129



"Changes in co-morbidities were assessed by each investigator by comparing the following categorical and noncategorical parameters to their preoperative status: (1) changes in


30

Study No.

Authors Proce-dure

RCT





therapy/medication (i.e., increased, decreased, discontinued, no change, could not assess); and/or (2) changes in diagnostic parameters (laboratory or test results) recorded in the medical records during follow-up and at the one-time prospective study visit. Using this combination of parameters, the investigators provided their assessment of changes in disease severity (e.g., no change, improved, worsened or could not assess); and current disease status (e.g., controlled, not controlled, resolved, or could not assess)."


AGB N 21 15

"The presence of comorbidities was defined by either the requirement for physician-prescribed medications…or such a diagnosis by the patient’s primary care physician."

“For the purposes of this study, ‘‘resolution’’ of a comorbidity was defined as the discontinuation of physician-prescribed medications postoperatively, and ‘‘improvement’’ was defined as a decreased dosage of physician-prescribed medications."

100183 Csendes A, Maluenda F, Burgos AM.

GB Y 12 10 Not Available

"Arterial hypertension [was assessed] taking 130/80 mmHg as the maximum normal value." GB Y 7 5

100264


GB Y 26 13 "Hypertension was diagnosed if the systolic blood pressure was 140 mm Hg and/or the diastolic blood pressure was 90 mm Hg."

"The co-morbidities were considered controlled if the patients required no medication and had normal blood test results during follow-up. The co-morbidities were considered improved if patients required less medication or had improved

GB Y 21 13


31

Study No.

Authors Proce-dure

RCT





blood test results compared with before surgery."

100296


GB N 781 702"Hypertension was defined when the blood pressure ≥140/90 mm Hg or when the patient was using any of the antihypertensive drugs..."

"...Improvement of hypertension meant a normalization of blood pressure levels or a reduction of antihypertensive medications." GB N 76 51

100297

Dixon JB, O'Brien PE, Playfair J, Chapman L, Schachter LM, Skinner S, et al.

AGB Y 20 14

Not Available Improvement was defined as a "reduction in use of antihypertensive agents”. Con-

trol Y 26 11


Com-bined

Y 23 18Not Available Not Available

GB Y 20 18

100405 Taylor CJ, Layani L. AGB N 28 19 Not Available.

"...Patients were…asked to participate in a detailed postoperative questionnaire package [with a] purpose-designed co-morbidity and medication survey, seeking information concerning change in 11 common obesity-related co-morbidities and medication requirements…Patients were asked to indicate which of 5 options (much worse/ worse/ same/better/much better) most accurately described changes in these co-morbidities... Changes in medication requirements were also sought (stopped taking/use less/use same/ use more/started taking).”

100412 Lee WJ, Wang W,Wei PL, Huang MT.

AGB N 43 17Hypertension was diagnosed if the patient presented with "blood pressure > 140/90mmHg or [a]

Not Available


32

Study No.

Authors Proce-dure

RCT





previous diagnosis of hypertension on pharmacologic treatment."

100452


GB N 12 8 Not Available

"Improvement in hypertension [and] diabetes… was determined by subjective symptomatic relief and assessment of the reduction or cessation of medication use."

100460


GB Y 19 13

Not Available

"Twelve of the 19 RYGBP patients (63.2%) who suffered from hypertension preoperatively were normotensive 2 years after surgery without any medication, and in one patient the dose of anti-hypertensive medication was decreased." Moreover, "of the 16 patients with hypertension in the BPD groups, 13 were normotensive at [the] second year follow-up (81.3%) and in one patient the dose of antihypertensive medication was decreased."

GB Y 16 14

100466


GB Y 18 15

Not Available


GB Y 28 28


33

Study No.

Authors Proce-dure

RCT





100471


GB N 82 54

Not Available

"Significant improvement was defined as less frequent symptoms or controlled with less medication, whereas resolution was defined as normal lab values, resolution of symptoms, or no medication."

AGB N 70 39

100493



Not Available AGB Y 7 2

100539

Silecchia G, Greco F, Bacci V, Boru C, Pecchia A, Casella G, et al.

AGB N 10 8Not Available Not Available

AGB N 10 2

100596


GB N 63 61 Not Available Not Available

200003



"Of the nine patients with Systemic Arterial Hypertension (SAH), two stopped taking medications and seven continued, but at lower doses than preoperatively."

200025 Matlach J, Adolf D,Benedix F, Wolff S.



200041


AGB N 49 30 Not Available Not Available

200043 Kasza J, Brody F, Vaziri K, Scheffey C,

AGB N 66 11 Not Available "...Partial resolution [was defined] with either dose


34

Study No.

Authors Proce-dure

RCT





McMullan S, Wallace B, et al.

reduction of medication or self reported improvement in symptoms."

300026



Postoperatively, 7 patients required treatment with lower doses and for 11 patients, treatment stopped.

300043


AGB N 9 7 Not Available.

"Antihypertensive treatment was no longer necessary in 7 (77.7%) of 9 patients with hypertension in the post-operative period."

300052

Batsis JA, Lopez-Jimenez F, Collazo-Clavell ML, Clark MM, Somers VK, Sarr MG.

GB N 126 48 "Hypertension was defined as blood pressure ≥ 130/80 mm Hg or use of medications with a hypertension history."

Not Available Con-trol

N 69 3

300071


AGB N 44 38Hyper tension was defined as blood pressure >140/90 mmHg.

Improvement was defined as having blood pressure “120–130 mmHg without pharmacological support".

300133 Parikh M, Duncombe J, Fielding GA.

AGB N 8 6


Postoperatively, "6 did not need medication".

300135


SG N 25 23 Not Available Not Available

300170 He M, Stubbs R. GB N 114 96

"Hypertension was deemed to be present if patients were taking antihypertensive medication or had a diastolic pressure in excess of 90 mmHg at hospital admission."

"Changes in comorbidities were classified as follows: · Resolution – normalisation of the comorbidities without requirement for medication. · Improvement—better control of the comorbidities with the same or reduced medication


35

Study No.

Authors Proce-dure

RCT





requirement. · No change—no evidence of resolution or improvement."

400034


AGB N 7 3

Not Available Not Available

VBG N 10 4

400048


SG N 50 41Not Available Not Available

SG N 79 69

400049 Behrens C, Tang BQ, Amson BJ.

SG N 17 17 Not Available


400050





Improvement was defined by "self-reported improvements (‘better” or ‘much better’) or deteriorations."


SG N 43 38

"Hypertension was diagnosed in 35.8% of the patients by means of a casual blood pressure measurement. All of [the patients] were using anti-hypertensive medications, mean of 1.4."

"The blood pressure normalized (≤130/≤85 mmHg), without medication, in 88.4% of the patients."


36

Study No.

Authors Proce-dure

RCT





400066



Postoperatively, "14 patients (77.8%) were corrected or decreased their pharmacological agent whereas one (15.5%) was stabilized."

400068 Hayes MT, Hunt LA, Foo J, Tychinskaya Y, Stubbs RS.

GB N 53 32Hypertension was diagnosed ifthe patient presented with the "presence of or [received] treatment for hypertension".

Not Available GB N 15 8


GB N 108 94

Initial diagnosis was classified into the following three classes: Moderate: Mild: "Diet controlled”; " Controlled with <2 medications"; Severe: "Controlled with ≥2 medications"

Not Available

400072


SG N 525 357

Not Available Not Available AGB N 5641 2482

GB N 7880 6225

400075


GB N 44 37

Not Available Not Available GB N 17 14

GB N 210 208

400100 Scopinaro N, Adami GF, Papadia FS, et al.

GB N 5 1"Hypertension was defined as a systolic blood pressure of ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg or chronically taking antihypertensive drugs."

Not Available Con-trol

N 13 4

400105 Tayyem R, ObondoC, Ali A.


400114 Boza C, Salinas J,Salgado N, et al.



SG N 60 30 Not Available "Resolution of hypertension...was defined as discontinuation of medications


37

Study No.

Authors Proce-dure

RCT





by the primary care physician."



"Of the 36 patients with hypertension, 22 (61%) had a reduction in their antihypertensive medication or no longer required them."

Dyslipidemia

100015

Herrera MF, Pantoja JP, Velazquez-Fernandez D, Cabiedes J, Aguilar-Salinas C, Garcia-Garcia E, et al.

GB Y 6 5

"Dyslipidemia was considered when measurements of triglycerides and/or cholesterol were above the upper normal limit values or when patients were under medical treatment with hypolipemiant drugs."

Not Available

GB Y 10 9


100129



"Changes in co-morbidities were assessed by each investigator by comparing the following categorical and noncategorical parameters to their preoperative status: (1) changes in therapy/ medication (i.e., increased, decreased, discontinued, no change, could not assess); and/or (2) changes in diagnostic parameters (laboratory or test results) recorded in the medical records during follow-up and at the one-time prospective study visit. Using this combination of parameters, the investigators provided their assessment of changes in disease severity (e.g., no change, improved, worsened or could not assess); and current disease status (e.g., controlled, not controlled,


38

Study No.

Authors Proce-dure

RCT





resolved, or could not assess)."

100264

Pinheiro JS, Schiavon CA, Pereira PB, Correa JL, Noujaim P, Cohen R

GB Y 52 30"Patients with lipid disorders presented with a total cholesterol of ≥240 mg/dL, low-density lipoprotein (LDL) of ≥130 mg/dL, high-density lipoprotein (HDL) of ≤40 mg/dL for men or ≤50 mg/dL for women, and/or triglyceride level ≥170 mg/dL.”

"The co-morbidities were considered controlled if the patients required no medication and had normal blood test results during follow-up. The co-morbidities were considered improved if patients required less medication or had improved blood test results compared with before surgery."

GB Y 41 29

100296


GB N 81 31"Dyslipidemia was diagnosed when either total cholesterol >5.2 mmol/l, high-density lipoprotein-cholesterol <0.9 mmol/l, or triglycerides >2.2 mmol/l (9) or when the patient was using any of the hypolipemic drugs..."

"...An improvement in dyslipidemia meant a normalization of lipid levels or a reduction of hypolipemic medications." GB N 26 10


Com-bined

Y 14 7Not Available Not Available

GB Y 13 8


GB Y 2 2 Not Available Not Available

100405 Taylor CJ, Layani L. AGB N 21 17 Not Available

"...Patients were again asked to participate in a detailed postoperative questionnaire package [with a] purpose-designed co-morbidity and medication survey, seeking information concerning change in 11 common obesity-related co-morbidities and medication requirements… Patients were asked to indicate which of 5 options (much worse/ worse/ same/ better/much better) most accurately described changes in


39

Study No.

Authors Proce-dure

RCT





these co-morbidities...Changes in medication requirements were also sought (stopped taking/use less/use same/ use more/started taking).”


AGB N 59 41

Hyperlipidemia was diagnosed when patients presented with "fasting triglycerides > 200 mg/dL and/or cholesterol > 200 mg/dL".

Not Available

100466


GB Y 8 7

Not Available


GB Y 14 14

100471


GB N 68 33

Not Available

"Significant improvement was defined as less frequent symptoms or controlled with less medication, whereas resolution was defined as normal lab values, resolution of symptoms, or no medication.”

AGB N 58 22

200003



"Of the four patients with hypertriglyceridemia, two are within normal triglyceride levels (<150 mg/dL)…”


AGB N 8 4 Not Available "Resolution of comorbidity was considered when medical treatment was no longer needed.


40

Study No.

Authors Proce-dure

RCT





Improvement of comorbidity was determined as reduced dose or combination of medications."

200041



300026



Postoperatively, 4 patients required "treatment with lower doses" and for 5 patients "treatment stopped".

300043



300052


GB N 107 58

"Dyslipidemia was defined as use of statins, fibrates, nicotinic acid, ezetimibe, or cholestyramine, or low-density lipoprotein cholesterol ≥160 mg/dL, triglycerides ≥150mg/dL, or high-density lipoprotein ≤ 40 mg/dL."

Not Available

Con-trol

N 63 2

300071


AGB N 22 12

Hyperlipidemia was diagnosed if the patient presented with "LDL cholesterol >250 mg/dl" and "Triglycerides >250 mg/dl".

Improvement was defined by "LDL cholesterol <200 mg/dl" and "Triglycerides <200 mg/dl…without pharmacological support"

300170 He M, Stubbs R. GB N 214 153

"Dyslipidaemia was judged present if one or more of the following abnormalities existed on fasting lipid profile. Total cholesterol >5.2 mmol/L, triglycerides >2.0 mmol/L, or total cholesterol/HDL cholesterol >5.0 mmol/L."

"Changes in comorbidities were classified as follows: · Resolution—normalisation of the comorbidities without requirement for medication. · Improvement—better control of the comorbidities with the same or reduced medication requirement.


41

Study No.

Authors Proce-dure

RCT





· No change—no evidence of resolution or improvement."






400066


SG N 18 12 Not Available "Twelve patients (66.7%) saw a correction or a decrease of their lipid disorders."

400075


GB N 36 31

Dyslipidemia was diagnosed if patients presented with "cholesterol>200 mg/dL, low density lipoprotein>190 mg/dL, high density lipoprotein<40 mg/dL in men and <50 mg/dL in women, [and] triglycerides>150 mg/dL"

Not Available

GB N 24 22

400105 Tayyem R, Obondo C, Ali A.


400114 Boza C, Salinas J, Salgado N, et al.


Cardiovascular disease

100129



"Changes in co-morbidities were assessed by each investigator by comparing the following categorical and noncategorical parameters to their preoperative


42

Study No.

Authors Proce-dure

RCT





status: (1) changes in therapy/ medication (i.e., increased, decreased, discontinued, no change, could not assess); and/or (2) changes in diagnostic parameters (laboratory or test results) recorded in the medical records during follow-up and at the one-time prospective study visit. Using this combination of parameters, the investigators provided their assessment of changes in disease severity (e.g., no change, improved, worsened or could not assess); and current disease status (e.g., controlled, not controlled, resolved, or could not assess)."

100493


VBG Y 3 2"Co-morbidities were recorded when patients were medically treated for the disorder."

Not Available


AGB N 9 7Cardiovascular disease was diagnosed when the patient was being treated with medication.


300052


GB N 17 1

"Cardiovascular disease was defined as patients with International Classification of Disease-9th Revision codes of 390-459.9."

"Improvement in co-morbidity was defined as patients with a baseline diagnosis no longer meeting follow-up diagnostic criteria."

Sleep apnea

100129 Toouli J, Kow L, Ramos AC, Aigner F, Pattyn P, Galvao-

AGB N 14 6 Not Available "Changes in co-morbidities were assessed by each investigator by comparing the following


43

Study No.

Authors Proce-dure

RCT





Neto MP, et al. categorical and noncategorical parameters to their preoperative status: (1) changes in therapy/ medication (i.e., increased, decreased, discontinued, no change, could not assess); and/or (2) changes in diagnostic parameters (laboratory or test results) recorded in the medical records during follow-up and at the one-time prospective study visit. Using this combination of parameters, the investigators provided their assessment of changes in disease severity (e.g., no change, improved, worsened or could not assess); and current disease status (e.g., controlled, not controlled, resolved, or could not assess)."


AGB N 19 15

"The presence of comorbidities was defined by either the requirement for physician-prescribed medications (or use of a continuous positive airway pressure [CPAP] mask in the case of obstructive sleep apnea) or such a diagnosis by the patient’s primary care physician."

"For the purposes of this study, ‘‘resolution’’ of a comorbidity was defined as the discontinuation of physician prescribed medications postoperatively, and ‘‘improvement’’ was defined as a decreased dosage of physician-prescribed medications."

100264


GB Y 11 11 "The sleep polysomnograph findings were the criteria for the diagnosis of sleep apnea"

"The co-morbidities were considered controlled if the patients required no medication and had normal blood test results during follow-up. The co-morbidities were considered improved if patients required less medication or had improved

GB Y 6 6


44

Study No.

Authors Proce-dure

RCT





blood test results compared with before surgery…All patients with sleep apnea no longer used CPAP."

100296


GB N 112 110

"Sleep apnea was diagnosed on the basis of the presence of subjective diurnal and/or nocturnal symptoms. An instrumental registration of the breathing pattern during sleep was not mandatory."

"Improvement of sleep apnea was acknowledged if there was a significant improvement in the subjective symptoms." GB N 34 34


GB Y 1 1 Not Available Not Available

100405 Taylor CJ, Layani L. AGB N 12 9 Not Available

"...Patients were again asked to participate in a detailed postoperative questionnaire package [with a] purpose-designed co-morbidity and medication survey, seeking information concerning change in 11 common obesity-related co-morbidities and medication requirements… Patients were asked to indicate which of 5 options (much worse/worse/same/better/much better) most accurately described changes in these co-morbidities...Changes in medication requirements were also sought (stopped taking/use less/use same/ use more/started taking).”



100425 Nelson WK, Fatima J,Houghton SG,



45

Study No.

Authors Proce-dure

RCT





Thompson GB, Kendrick ML, Mai JL, et al.

100452


GB N 9 7 Not Available

"For patients with obstructive sleep apnea, improvement was verified by cessation of the use of continuous positive airway pressure or by postoperative sleep study findings."

100460


GB Y 3 3Not Available Not Available

GB Y 1 1

100466


GB Y 5 5

Not Available

"Changes in comorbidities were analyzed according to the following scale… A designation of improved was assigned if the patient experienced decreased severity or frequency of symptoms or decreased dosage or number of medications. A designation of resolved was assigned if the patient had resolution of symptoms and did not require medication for treatment. In the case of sleep apnea, the use of continuous positive airway pressure mask was considered treatment in lieu of medication."

GB Y 15 12

100493



Not Available AGB Y 1 1

100539 Silecchia G, Greco F, Bacci V, Boru C, Pecchia A, Casella

AGB N 1 1Not Available Not Available

AGB N 1 1


46

Study No.

Authors Proce-dure

RCT





G, et al.

100596






200041



200043

Kasza J, Brody F, Vaziri K, Scheffey C, McMullan S, Wallace B, et al.


"Partial resolution [was defined] with either dose reduction of medication or self-reported improvement in symptoms."

300133 Parikh M, DuncombeJ, Fielding GA.

AGB N 7 6


Postoperatively, "6 [patients with sleep apnea] did not need mask".

300135



300170 He M, Stubbs R. GB N 61 59

"OSA was deemed present if patients had been formally diagnosed prior to consultation or they admitted to symptoms suggestive of the diagnosis—such as snoring, disturbed, or restless sleep with apnoeic episodes accompanied by daytime somnolence and chronic

"Changes in comorbidities were classified as follows: · Resolution—normalisation ofthe comorbidities without requirement for medication. · Improvement—better control ofthe comorbidities with the same or reduced medication requirement.


47

Study No.

Authors Proce-dure

RCT





fatigue." · No change—no evidence of resolution or improvement."

400034


AGB N 1 1

Not Available Not Available VBG N 1 1

400048


SG N 29 24Not Available Not Available

SG N 39 35



Resolution of obstructive sleep apnea (OSA) was determined by follow-up assessment by respirologists or internists.

400050





Improvement was defined by "self-reported improvements (‘better’ or “much better’) or deteriorations."




GB N 45 34

Sleep apnea diagnosis was divided into the following three classes: Mild: "Mild symptoms only"; Moderate: "Diagnosed with sleep study but no CPAP"; Severe: "Diagnosed with sleep study and need for CPAP"

Not Available

400072


SG N 323 200

Not Available Not Available AGB N 3477 1321

GB N 5239 3458


48

Study No.

Authors Proce-dure

RCT





400075


GB N 6 6

Not Available Not Available GB N 10 10

GB N 127 127

400105 Tayyem R, ObondoC, Ali A.




"Resolution of sleep apnea was defined as the discontinued need for continuous positive airway pressure machine use."



"...All 25 patients with obstructive sleep apnea no longer required continuous positive airway pressure."

GB: gastric bypass; AGB: adjustable gastric banding; VBG: vertical banded gastroplasty; SG: sleeve gastrectomy; Control: non-surgical interventions; Y: yes; N: no.


49

eTable 2 Summary of surgery types and categories

Surgery Composition of surgical procedures and treatment strategies Category # and name

1 Laparoscopic Roux-en-Y Gastric Bypass (LRYGB), long limb (LRGYB- long), LRYGB, short limb (LRGYB-short), LRYGB, limb mixed lengths (LRGYB-mixed)

1 Gastric bypass (GB)

2 Open RYGB, long limb (ORYGB-long), Open RYGB, short limb (ORYGB-short) 3 LRYGB with presurgery weight loss (LRGYB, presurgery weight loss) 4 Laparoscopic biliopancreatic diversion with duodenal switch (LBD-DS) 5 Biliopancreatic diversion with RYGB (BPD-RYGB)

6 Laparoscopic adjustable gastric banding (LAGB), lapband, pars flaccida technique (LLAGB-PF), LAGB, lapband, perigastric technique (LLAGB-PG), LAGB, technique not specified (LAGB-NS)

2 Adjustable gastric banding (AGB)

7 LSAGB, Swedish, pars flaccida technique (LSAGB-PF), LSAGB, pars flaccida technique, single bolus filling (LSAGB-PF-BF)

8 Laparoscopic vertical banded gastroplasty (LVBG) 3 Vertical banded gastroplasty (VBG) 9 Open vertical banded gastroplasty (OVBG)

10 Laparoscopic sleeve gastrectomy (SG) 4 Sleeve gastrectomy (SG)

11 Nonsurgical intervention 5 Control


50

eTable 3. Meta-analyses of surgery risk and comorbidities remission outcomes

GB AGB VBG SG Control Overall

BA BH BA BH BA BH BA BH BA BH BA BHMortality ≤ 30 days

RCT

Mean (%) 0.08 0.11 0.11 0.06 0.78 0.00 0.50 0.00 -- -- 0.08 0.08

2.50% 0.01 0.00 0.01 0.05 0.01 -- 0.01 -- -- -- 0.01 0.00

97.5% 0.30 0.32 0.50 0.18 5.43 -- 3.88 -- -- -- 0.24 0.21

# of arms 18 8 1 2 0 30

# of patients 934 743 40 40 0 1,803

OBS

Mean (%) 0.38 0.64 0.07 0.12 0.49 0.25 0.29 0.54 2.14 0.00 0.22 0.39

2.50% 0.22 0.39 0.02 0.00 0.01 -- 0.11 0.04 0.01 -- 0.14 0.26

97.5% 0.59 0.89 0.12 0.24 2.36 -- 0.63 1.03 17.92 -- 0.31 0.52

# of arms 30 29 2 11 1 79

# of patients 90,090 40,538 240 3,647 9 136,903 Mortality > 30 days

RCT

Mean (%) 0.39 0.40 0.14 0.07 21.00 4.00 6.00 0.00 -- -- 0.31 0.40

2.50% 0.01 0.00 0.00 0.00 0.00 0.00 0.00 -- -- -- 0.01 0.07

97.5% 0.86 0.80 0.55 0.20 100.00 9.43 100.00 -- -- -- 0.75 0.73

# of arms 19 7 1 2 0 30

# of patients 954 613 50 40 0 1,703

OBS

Mean (%) 0.72 1.34 0.21 0.29 4.3 0.09 0.34 0.27 -- -- 0.35 0.65

2.50% 0.28 0.53 0.08 0.07 0.00 -- 0.14 0.03 -- -- 0.20 0.34

97.5% 1.30 2.16 0.37 0.51 100.00 -- 0.60 0.52 -- -- 0.52 0.95

# of arms 18 22 2 9 0 51

# of patients 29,256 33,950 592 3,099 0 66,897 Complication rates

RCT

Mean (%) 21.00 24.27 13.00 15.87 20.00 24.78 13.00 12.81 20.00 -- 17.00 20.52

2.50% 12.00 17.57 5.20 9.28 1.50 0.00 0.70 0.00 0.98 -- 11.00 16.14

97.5% 33.00 30.97 26.00 22.46 63.00 56.03 44.00 30.05 68.00 -- 23.00 24.89

# of arms 14 11 2 2 2 30

# of patients 649 855 91 137 59 1,778


51


BA BH BA BH BA BH BA BH BA BH BA BH

OBS

Mean (%) 12.00 16.40 7.80 12.92 40.00 41.41 8.90 10.86 -- -- 9.80 14.45

2.50% 7.30 12.13 3.90 9.09 8.90 15.69 5.60 8.52 -- -- 7.40 12.17

97.5% 17.00 20.67 13.00 16.75 83.00 67.14 13.00 13.21 -- -- 13.00 16.73

# of arms 28 24 2 20 0 74

# of patients 71,020 36,778 217 4,987 0 113,002Reoperation rates

RCT

Mean (%) 2.56 3.30 12.23 16.46 20.14 20.41 9.05 9.99 -- -- 6.95 11.84

2.50% 0.61 0.96 4.46 9.17 4.50 8.13 0.77 0.00 -- -- 3.27 7.76

97.5% 5.36 5.64 24.46 23.74 51.35 32.69 34.56 21.45 -- -- 12.04 15.91

# of arms 8 10 3 2 0 23

# of patients 512 502 147 161 0 1,322

OBS

Mean (%) 5.34 5.61 7.01 10.45 11.25 12.51 2.96 3.45 -- -- 5.75 8.36

2.50% 4.48 4.07 3.99 7.52 1.96 2.90 1.70 1.99 -- -- 4.05 6.50

97.5% 6.48 7.15 11.24 13.38 31.26 22.12 4.71 4.91 -- -- 7.83 10.21

# of arms 8 21 3 7 0 39

# of patients 23,688 30,314 257 2,912 0 57,171Diabetes remission rates

RCT

Mean (%) 95.15 93.46 73.88 76.67 82.62 85.71 -- -- 17.64 13.33 91.99 90.38

2.50% 88.38 88.05 36.06 63.26 27.18 59.79 -- -- 0.98 1.17 84.68 85.02

97.5% 98.80 98.86 96.18 90.07 99.79 111.64 -- -- 69.27 25.50 97.18 95.73

# of arms 10 2 1 0 1 14

# of patients 152 35 7 0 30 206

OBS

Mean (%) 92.83 84.13 67.58 62.75 97.27 100.00 85.53 78.32 -- -- 86.05 75.75

2.50% 85.29 77.17 49.51 52.78 76.89 -- 72.69 69.98 -- -- 78.74 70.73

97.5% 97.21 91.09 82.83 72.71 100.00 -- 94.07 89.65 -- -- 91.62 80.78

# of arms 22 19 1 15 0 57

# of patients 5,924 2,509 7 597 0 9,037

Hypertension remission rates

RCT Mean (%) 80.98 78.04 53.55 49.29 33.34 30.00 -- -- 49.00 -- 75.18 71.02

2.50% 68.21 70.06 12.52 17.61 2.19 1.60 -- -- 0.00 -- 61.52 62.74


52


BA BH BA BH BA BH BA BH BA BH BA BH97.5% 91.52 86.02 89.63 80.96 87.42 58.40 -- -- 99.00 -- 86.35 79.29

# of arms 11 2 1 0 1 15

# of patients 183 27 10 0 27 243

OBS

Mean (%) 78.13 71.59 63.73 63.01 41.00 40.00 82.23 78.00 15.00 17.56 74.36 69.09

2.50% 63.67 63.68 51.74 55.36 3.60 9.64 68.19 71.18 1.40 0.00 66.53 64.49

97.5% 88.76 79.50 75.43 70.65 92.00 70.36 92.01 84.82 53.00 38.56 81.19 73.68

# of arms 15 19 1 12 2 47

# of patients 9,586 6,214 10 1,152 82 16,962Dyslipidemia remission rates

RCT

Mean (%) 80.16 79.91 39.95 37.88 -- -- -- -- -- -- 75.77 75.24

2.50% 61.68 70.15 4.69 29.60 -- -- -- -- -- -- 55.63 64.53

97.5% 94.19 89.66 87.05 46.15 -- -- -- -- -- -- 91.49 85.94

# of arms 8 1 0 0 0 9

# of patients 147 132 0 0 0 279

OBS

Mean (%) 63.22 61.25 60.91 61.23 -- -- 82.86 79.75 5.42 -- 67.93 65.26

2.50% 40.86 49.59 49.45 52.46 -- -- 62.67 69.40 0.12 -- 58.08 59.01

97.5% 82.34 72.90 72.36 69.99 -- -- 94.55 90.10 30.41 -- 77.01 71.51

# of arms 7 11 0 5 1 23

# of patients 556 351 0 570 63 1,477Cardiovascular disease remission rates

RCT

Mean (%) -- -- -- -- 64.53 66.67 -- -- -- -- 65.81 66.67

2.50% -- -- -- -- 6.19 13.32 -- -- -- -- 6.21 13.32

97.5% -- -- -- -- 99.29 100.00 -- -- -- -- 99.46 100.00

# of arms 0 0 1 0 0 1

# of patients 0 0 3 0 0 3

OBS

Mean (%) 22.00 5.88 78.00 88.89 -- -- -- -- -- -- 58.00 61.22

2.50% 0.00 0.00 0.00 -- -- -- -- -- -- -- 0.00 24.11

97.5% 100.00 17.07 100.00 -- -- -- -- -- -- -- 100.00 98.33

# of arms 1 2 0 0 0 3


53


BA BH BA BH BA BH BA BH BA BH BA BH# of patients 17 10 0 0 0 27

Sleep apnea remission rates

RCT

Mean (%) 95.41 96.67 94.26 100.00 88.68 100.00 -- -- -- -- 96.16 97.78

2.50% 84.49 91.80 49.43 -- 14.22 -- -- -- -- -- 86.66 94.57

97.5% 99.79 100.00 100.00 -- 100.00 -- -- -- -- -- 99.80 100.00

# of arms 6 2 1 0 0 9

# of patients 41 2 1 0 0 44

OBS

Mean (%) 94.68 87.50 71.14 70.14 89.16 100.00 90.77 89.80 -- -- 89.53 81.51

2.50% 86.36 79.70 48.29 58.67 16.69 -- 80.06 83.93 -- -- 81.33 75.77

97.5% 98.72 95.30 89.16 81.62 100.00 -- 97.39 95.67 -- -- 95.08 87.24

# of arms 11 14 1 9 0 35

# of patients 5,748 3,598 1 498 0 9,845Arms refer to subgroups within studies receiving different surgical procedures. GB: gastric bypass; AGB: adjustable gastric banding; VBG: vertical banded gastroplasty; SG: sleeve gastrectomy; Control: non-surgical interventions (non-surgical interventions were included in the analyses only when they were compared with surgical interventions); Overall: all surgery except for Control; BA: estimates were computed using Bayesian random-effects meta-analysis estimation method; BH: estimates were computed using random-effects meta-analysis estimation method proposed by Bhaumik et al. (2012); RCT: randomized controlled trial; OBS: observational study; 2.50%: lower limit of the 95% credit/confidence interval for BA/BH; 97.5%: upper limit of the 95% credit/confidence interval for BA/BH; --: estimates are not available. Remission rate is defined as the proportion of the surgery patients who reported the target comorbid condition being either resolved or improved after surgery. For the 2.5% and 97.5% values of BH, we used 0 or 100 if they are outside of the range of 0-100.


54

eTable 4. Meta-analyses of weight change outcomes GB AGB VBG SG Control Overall

FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE

∆BMI (year 1)

RCT

Estimate -14.72 -14.53 -10.48 -10.48 -13.50 -13.50 -16.20 -16.20 -- -- -13.91 -13.53

2.50% -16.09 -16.82 -13.70 -13.70 -22.46 -22.46 -24.45 -24.45 -- -- -15.13 -15.51

97.5% -13.34 -12.25 -7.25 -7.25 -4.53 -4.53 -7.95 -7.95 -- -- -12.68 -11.55

I2 (%) 58 0 0 -- -- 55

# of arms 15 3 2 1 0 22

OBS

Estimate -9.57 -14.32 -7.53 -7.70 -8.00 -8.00 -11.95 -12.14 -1.01 -1.01 -9.63 -11.79

2.50% -10.48 -19.02 -8.51 -9.37 -13.71 -13.71 -13.29 -14.02 -5.26 -5.26 -10.21 -13.89

97.5% -8.66 -9.62 -6.55 -6.03 -2.29 -2.29 -10.62 -10.26 3.23 3.23 -9.04 -9.69

I2 (%) 96 57 0 34 0 92

# of arms 37 27 3 18 4 87

∆BMI (year 2)

RCT

Estimate -14.49 -14.47 -11.35 -11.35 -14.89 -14.89 -- -- -- -- -13.22 -13.23

2.50% -16.51 -16.98 -14.24 -14.24 -21.62 -21.62 -- -- -- -- -14.80 -15.36

97.5% -12.47 -11.97 -8.46 -8.46 -8.16 -8.16 -- -- -- -- -11.63 -11.11

I2 (%) 19 0 0 -- -- 30

# of arms 10 2 2 0 0 15

OBS

Estimate -11.97 -12.93 -8.59 -8.75 -16.91 -16.91 -12.64 -13.39 0.10 0.10 -10.88 -11.80

2.50% -13.49 -17.39 -10.05 -10.37 -22.03 -22.03 -16.76 -19.53 -7.39 -7.39 -11.87 -13.92

97.5% -10.44 -8.47 -7.12 -7.13 -11.78 -11.78 -8.52 -7.26 7.60 7.60 -9.90 -9.69

I2 (%) 86 12 0 49 0 75

# of arms 16 16 2 5 2 40

∆BMI (year 3)

RCT

Estimate -- -- -9.20 -9.20 -- -- -- -- -- -- -9.20 -9.20

2.50% -- -- -15.85 -15.85 -- -- -- -- -- -- -15.85 -15.85

97.5% -- -- -2.54 -2.54 -- -- -- -- -- -- -2.54 -2.54

I2 (%) -- 0 -- -- -- 0

# of arms 0 2 0 0 0 2


55


FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE

OBS

Estimate -16.72 -16.78 -11.72 -11.43 -17.00 -17.00 -21.88 -21.88 -- -- -15.50 -15.48

2.50% -20.24 -20.57 -15.27 -18.14 -29.02 -29.02 -27.96 -27.96 -- -- -17.73 -18.79

97.5% -13.21 -12.99 -8.18 -4.72 -4.98 -4.98 -15.79 -15.79 -- -- -13.27 -12.18

I2 (%) 13 14 -- 0 -- 53

# of arms 9 8 1 2 0 21

∆BMI (year 4)

RCT

Estimate -- -- -- -- -- -- -- -- -- -- -- --

2.50% -- -- -- -- -- -- -- -- -- -- -- --

97.5% -- -- -- -- -- -- -- -- -- -- -- --

I2 (%) -- -- -- -- -- --

# of arms 0 0 0 0 0 0

OBS

Estimate -18.12 -17.86 -6.20 -6.20 -16.00 -16.00 -- -- -- -- -17.25 -17.00

2.50% -21.87 -22.20 -18.62 -18.62 -30.27 -30.27 -- -- -- -- -20.61 -20.80

97.5% -14.37 -13.53 6.22 6.22 -1.73 -1.73 -- -- -- -- -13.90 -13.19

I2 (%) 23 -- -- -- -- 20

# of arms 8 1 1 0 0 11

∆BMI (year 5)

RCT

Estimate -- -- -11.40 -11.40 -- -- -- -- -- -- -11.40 -11.40

2.50% -- -- -28.08 -28.08 -- -- -- -- -- -- -28.08 -28.08

97.5% -- -- 5.28 5.28 -- -- -- -- -- -- 5.28 5.28

I2 (%) -- -- -- -- -- --

# of arms 0 1 0 0 0 1

OBS

Estimate -15.90 -15.96 -12.41 -12.36 -16.00 -16.00 -16.10 -16.10 -- -- -14.31 -14.32

2.50% -20.11 -20.52 -16.53 -16.92 -28.79 -28.79 -28.22 -28.22 -- -- -17.10 -17.19

97.5% -11.69 -11.40 -8.30 -7.79 -3.21 -3.21 -3.98 -3.98 -- -- -11.52 -11.45

I2 (%) 14 18 -- -- -- 5

# of arms 7 7 1 1 0 16

%EWL (year 1) RCT Estimate 78.82 72.32 33.39 33.39 64.30 64.30 69.70 69.70 -- -- 76.90 59.82


56


FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE2.50% 76.63 64.60 22.57 22.57 28.88 28.88 41.09 41.09 -- -- 74.77 50.46

97.5% 81.00 80.04 44.21 44.21 99.72 99.72 98.32 98.32 -- -- 79.03 69.17

I2 (%) 77 0 0 -- -- 85

# of arms 7 4 2 1 0 15

OBS

Estimate 39.08 63.31 34.26 34.26 47.71 51.93 47.04 51.49 20.00 20.00 34.55 46.16

2.50% 37.38 54.20 33.98 33.98 43.94 39.79 43.82 44.41 -25.08 -25.08 34.28 43.89

97.5% 40.77 72.43 34.54 34.54 51.47 64.06 50.27 58.56 65.08 65.08 34.82 48.43

I2 (%) 88 0 53 38 -- 90

# of arms 25 15 3 11 1 55

%EWL (year 2)

RCT

Estimate 78.33 74.39 53.58 53.58 65.07 65.07 -- -- -- -- 77.82 70.58

2.50% 75.83 66.22 32.80 32.80 23.13 23.13 -- -- -- -- 75.35 62.67

97.5% 80.83 82.55 74.87 74.87 107.02 107.02 -- -- -- -- 80.30 78.50

I2 (%) 75 0 0 -- -- 63

# of arms 6 3 2 0 0 12

OBS

Estimate 87.03 80.09 52.29 52.29 73.05 73.05 46.72 46.72 -- -- 65.98 63.98

2.50% 80.54 65.74 48.67 48.67 71.10 71.10 42.89 42.89 -- -- 64.46 55.21

97.5% 93.52 94.43 55.92 55.92 75.00 75.00 50.55 50.55 -- -- 67.50 72.74

I2 (%) 47 0 0 0 -- 90

# of arms 9 11 3 3 0 27

%EWL (year 3)

RCT

Estimate -- -- 56.72 56.72 -- -- -- -- -- -- 56.72 56.72

2.50% -- -- 51.59 51.59 -- -- -- -- -- -- 51.59 51.59

97.5% -- -- 61.85 61.85 -- -- -- -- -- -- 61.85 61.85

I2 (%) -- 0 -- -- -- 0

# of arms 0 2 0 0 0 2

OBS

Estimate 76.35 76.35 58.30 58.30 66.99 66.99 59.42 59.42 -- -- 66.93 66.93

2.50% 65.21 65.21 42.12 42.12 65.03 65.03 48.05 48.05 -- -- 65.05 65.05

97.5% 87.50 87.50 74.49 74.49 68.95 68.95 70.78 70.78 -- -- 68.82 68.82


57


FFE FRE FFE FRE FFE FRE FFE FRE FFE FRE FFE FREI2 (%) 0 0 0 0 -- 0

# of arms 8 6 2 2 0 19

%EWL (year 4)

RCT

Estimate -- -- -- -- -- -- -- -- -- -- -- --

2.50% -- -- -- -- -- -- -- -- -- -- -- --

97.5% -- -- -- -- -- -- -- -- -- -- -- --

I2 (%) -- -- -- -- -- --

# of arms 0 0 0 0 0 0

OBS

Estimate 85.00 76.36 81.17 74.91 69.00 69.00 -- -- -- -- 71.79 74.82

2.50% 78.38 59.02 76.49 58.54 67.04 67.04 -- -- -- -- 70.05 65.85

97.5% 91.62 93.70 85.86 91.29 70.96 70.96 -- -- -- -- 73.54 83.80

I2 (%) 66 41 -- -- -- 83

# of arms 5 3 1 0 0 10

%EWL (year 5)

RCT

Estimate -- -- 41.60 41.60 -- -- -- -- -- -- 41.60 41.60

2.50% -- -- -9.75 -9.75 -- -- -- -- -- -- -9.75 -9.75

97.5% -- -- 92.95 92.95 -- -- -- -- -- -- 92.95 92.95

I2 (%) -- -- -- -- -- --

# of arms 0 1 0 0 0 1

OBS

Estimate 62.62 64.92 57.23 57.23 62.98 62.98 -- -- -- -- 62.24 62.24

2.50% 48.43 44.27 47.23 47.23 59.07 59.07 -- -- -- -- 58.71 58.71

97.5% 76.82 85.58 67.23 67.23 66.90 66.90 -- -- -- -- 65.78 65.78

I2 (%) 36 0 0 -- -- 0

# of arms 5 8 2 0 0 15Arms refer to subgroups within studies receiving different surgical procedures. GB: gastric bypass; AGB: adjustable gastric banding; VBG: vertical banded gastroplasty; SG: sleeve gastrectomy; Control: non-surgical interventions (non-surgical interventions were included in the analyses only when they were compared with surgical interventions); Overall: all surgery except for Control; FFE: estimates were obtained from fixed-effect models using the Frequentist approach; FRE: estimates were obtained from random-effects models using the Frequentist approach; RCT: randomized controlled trials; OBS: observational studies; 2.50%: lower limit of the 95% confidence interval; 97.5%: upper limit of the 95% confidence interval; BMI: body mass index; ∆BMI: BMI change; %EWL: percent excess weight loss; --: estimates are not available.


58

eTable 5 Meta-regression results: BMI change

(kg/m2) ∆BMI (year 1) ∆BMI (year 2) Estimates p-values Estimates p-values Patient characteristics Age 0.27 (0.06) 0.0000 0.30 (0.10) 0.0070 % female 0.02 (0.02) 0.2610 0.02 (0.06) 0.7080 BMI -0.41 (0.06) 0.0000 -0.37 (0.14) 0.0140 Study design RCT -11.46 (2.33) 0.0000 -2.28 (2.66) 0.3990 Study quality Clearly defined surgery -0.36 (0.83) 0.6630 -0.52 (1.81) 0.7770 Clear time points 0.27 (0.81) 0.7410 2.00 (1.49) 0.1910 Adjustment of confounders -1.72 (1.06) 0.1090 -2.60 (2.40) 0.2890 Adequate randomization 9.97 (2.16) 0.0000 -- (--) -- Sample size calculation 4.60 (1.36) 0.0010 5.44 (2.92) 0.0730 Loss to follow-up reported and >20% -0.47 (1.02) 0.6490 -8.23 (3.23) 0.0170 Loss to follow-up <20% 1.41 (1.08) 0.1980 5.48 (2.91) 0.0700 Funding reported but linked to industry 2.37 (1.91) 0.2180 0.62 (3.44) 0.8590 Funding not linked to industry -0.54 (1.83) 0.7700 3.38 (3.53) 0.3460 Surgical procedure AGB 5.13 (0.93) 0.0000 2.99 (1.96) 0.1390 VBG 5.94 (2.25) 0.0100 0.49 (2.43) 0.8410 SG 2.54 (1.04) 0.0170 -2.86 (3.03) 0.3530 Control 9.69 (2.48) 0.0000 -- (--) -- Combined -0.44 (3.61) 0.9030 2.44 (7.21) 0.7370 Location North America 1.18 (1.49) 0.4310 0.81 (2.87) 0.7810 Europe 1.10 (1.30) 0.4010 -0.42 (2.24) 0.8530 Asia 3.30 (1.88) 0.0830 2.95 (2.06) 0.1630 Standard errors are in parentheses.


59

eTable 6 MTC Model 1 estimates: relative surgery effects (∆BMIa) to LRYGB

(kg/m2)

Surgery Meanb Standard deviation 2.50%c Median 97.50%d

1 -- -- -- -- --

2 1.62 2.88 -4.32 1.64 7.41

3 -1.72 4.23 -10.48 -1.68 6.66

4 -3.99 4.03 -11.90 -4.03 4.45

5 -1.86 4.99 -12.33 -1.68 8.19

6 9.00 2.39 4.09 8.97 13.77

7 10.00 4.76 0.22 10.03 19.44

8 3.12 2.43 -1.84 3.14 7.84

9 4.99 4.80 -5.00 5.11 14.07

10 0.29 2.96 -5.54 0.23 6.40

11 13.99 3.85 6.27 13.93 21.89a. ∆BMI=post-surgery BMI-pre-surgery BMI; b. a negative value means that LRYGB was outperformed in terms of BMI loss and vice versa; c.lower limit of the 95% credible interval; d. upper limit of the 95% credible interval.

eTable 7 MTC Model 2 estimates: relative surgery effects (∆BMIa) to surgery category GB

(kg/m2)

Category Meanb Standard deviation 2.50%c Median 97.50%d

GB -- -- -- -- --

AGB 8.835 1.802 5.178 8.845 12.440

VBG 3.432 1.827 -0.151 3.419 7.169

SG 0.270 2.360 -4.413 0.314 4.897

Control 13.750 2.929 7.865 13.770 19.610a. ∆BMI=post-surgery BMI-pre-surgery BMI; b. a positive value means that GB outperformed in terms of BMI loss and vice versa; c. lower limitof the 95% credible interval; d. upper limit of the 95% credible interval.


60


(kg/m2)

Surgery Meanb Standard deviation 2.50%c Median 97.50%d

1 -- -- -- -- --

2 -0.302 3.202 -6.157 -0.408 6.422

3 -1.320 3.486 -8.088 -1.398 5.980

4 -1.687 3.529 -8.506 -1.739 5.640

5 -1.583 3.899 -9.368 -1.618 6.595

GB -1.254 3.283 -7.743 -1.387 5.693

6 3.718 2.523 -1.305 3.686 8.850

7 3.907 3.834 -3.790 3.782 11.890

AGB 3.811 3.614 -3.549 3.702 11.238 0.598 3.021 -5.148 0.582 6.923

9 0.485 3.967 -7.526 0.584 8.238

VBG 0.606 3.892 -7.224 0.661 8.24610 -0.261 0.613 -1.367 -0.281 0.862

SG -0.261 0.613 -1.367 -0.281 0.862

11 0.235 0.995 -1.934 0.566 1.491

Control 0.235 0.995 -1.934 0.566 1.491a. ∆BMI=post-surgery BMI-pre-surgery BMI; b. a negative value means that LRYGB was outperformed in terms of BMI loss and vice versa; c.lower limit of the 95% credible interval; d. upper limit of the 95% credible interval.


61


(kg/m2)

Time interval Surgery Meanb Standard deviation 2.50%c Median 97.50%d

<1 year

1 -- -- -- -- --

2 4.470 6.054 -7.463 4.423 16.580

3 -1.613 4.360 -10.490 -1.595 6.699

4 -3.043 5.997 -15.010 -3.053 8.611

5 -0.689 98.720 -194.500 -0.592 194.800

6 3.606 51.730 -89.800 0.224 101.800

7 5.524 51.810 -87.540 2.223 104.600

8 1.474 4.985 -8.170 1.459 11.370

9 -0.747 51.820 -93.550 -4.167 98.450

10 0.379 3.830 -7.281 0.419 7.706

11 3.679 52.240 -90.330 -0.065 105.500

≥ 1 and <3 years

1 -- -- -- -- --

2 1.840 4.337 -6.68 1.842 10.37

3 2.016 99.760 -192.60 2.431 194.10

4 -6.374 8.664 -23.46 -6.493 10.88

5 -1.578 7.496 -16.41 -1.675 13.58

6 6.361 4.093 -1.48 6.34 14.52

7 0.528 97.040 -201.50 1.491 185.2

8 2.102 4.119 -5.90 2.037 10.19

9 2.967 7.174 -11.27 2.937 17.11

10 -1.189 8.544 -18.11 -1.098 16.20

11 11.310 5.914 -0.63 11.300 23.10

≥3 years

1 -- -- -- -- --

2 4.064 8.632 -13.01 4.041 21.52

3 0.348 100.500 -200.80 1.543 193.30

4 0.426 97.410 -186.30 0.599 190.60

5 0.016 99.140 -187.60 -2.142 199.60

6 20.170 4.243 11.70 20.170 28.52

7 1.328 99.910 -192.20 1.274 202.40

8 15.550 6.058 3.37 15.660 27.47

9 -1.237 101.600 -199.70 -0.614 199.60

10 -2.482 100.900 -201.20 -1.311 194.50

11 30.559 98.930 -163.80 30.703 226.70a. ∆BMI=post-surgery BMI-pre-surgery BMI; b. a negative value means that LRYGB was outperformed in terms of BMI loss and vice versa; c.lower limit of the 95% credible interval; d. upper limit of the 95% credible interval.


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eTable 10 A comparison of findings across the systematic reviews and meta-analyses of bariatric surgery Buchwald et al. (2004) Maggard et al. (2005) Padwal et al. (2011) Our study Databases MEDLINE, Current Contents,

and the Cochrane Library MEDLINE and EMBASE MEDLINE, EMBASE,

CENTRAL, and PubCraweler alert

MEDLINE, EMBASE, SCOPUS, Current Contents, Cochrane Library, and Clinicaltrials.gov

Search time period

1990-June, 2003 Prior to July, 2003 1950-March, 2010 2003-March, 2012

Study design included

Any design including RCTs and non-RCTs

RCTs, controlled clinical trials, cohort studies, and case series

RCTs Any design including RCTs and OBSs

Studies included

136 147 31 164

Meta-analytic methods

Weight loss, mortality, and comorbidity: Frequentist RE meta-analysis and weighted (by sample size) mean

Weight loss: Frequentist RE meta-analysis (pooled mean difference); Mortality: crude proportions and zeros were imputed for missing data; Comorbidity: crude proportions; Complication: pooled odds ratios and crude proportions.

Weight loss: Bayesian Network analysis; Mortality, complication, and comorbidity analysis: pooled risk ratio and risk difference (RD).

Weight loss: Frequentist RE/FE meta-analysis, and meta-regression, Bayesian MTC analysis with repeated measurement; Mortality, complication, and comorbidity analysis: Bayesian and Frequentist (Bhaumik) RE meta-analysis.

Mortality outcomes

≤30 days mortality: 0.1% for the purely restrictive procedures, 0.5% for GB, and 1.1% for BPD or DS

≤30 days mortality: 0.4% for AGB in controlled trials and 0.02% for case series; 1% for RYGB in controlled trials and 0.3% for case series. >30 days mortality: 0.1% for AGB in case series; 1.1% for RYGB in controlled trials and 0.6% for case series; 0.3% for BPD in case series.

Not available. ≤30 days mortality: 0.08% in RCTs and 0.38% in OBSs for GB; 0.11% in RCTs and 0.07% in OBSs for AGB. >30 days mortality: 0.42% in RCTs and 0.72% in OBSs for GB; 0.14% in RCTs and 0.21% in OBSs for AGB.

Comorbidity outcomes

Diabetes: 86% patients resolved or improved; 47.9% for AGB; 83.7% for GB; 98.9% for BPD or DS. Hyperlipidemia: 79.3% patients resolved or improved; 58.9% for AGB; 96.9% for GB; 99.1% for BPD or DS.

Reported but no meta-analysis results.

Not reported. Diabetes: 86% patients resolved or improved in OBSs (92% in RCTs); 92.9% for GB in OBSs (95.2% in RCTs); 67.6% for AGB in OBSs (73.9% in RCTs). Dyslipidemia: 67.9% patients resolved or improved in


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Hypertension: 78.5% patients resolved or improved; 70.8% for AGB; 87.2% for GB; 75.1% for BPD or DS. Sleep apnea: 83.6% patients resolved or improved; 68% for AGB; 94.8% for GB; 71.2% for BPD or DS.

OBSs (75.8% in RCTs); 63.2% for GB in OBSs (80.2% in RCTs); 60.9% for AGB in OBSs (40.0% in RCTs). Hypertension: 74.4% patients resolved or improved in OBSs (75.2% in RCTs); 78.1% for GB in OBSs (81% in RCTs); 63.7% for AGB in OBSs (53.6% in RCTs). Sleep apnea: 89.5% patients resolved or improved in OBSs (96.2% in RCTs); 94.7% for GB in OBSs (95.4% in RCTs); 71.1% for AGB in OBSs (94.3% in RCTs).

Complication outcomes

Not available. Combining all studies, Gastrointestinal symptoms: 16.9% for RYGB; 7% for AGB; 37.7% for BPD. Reflux: 10.9% for RYGB; 4.7% for AGB. Vomiting: 15.7% for RYGB; 2.5% for AGB. Nutritional and electrolyte abnormalities: 16.9% for RYGB. Leak: 2.2% for RYGB. Stenosis: 4.6% for RYGB. Bleeding: 2% for RYGB; 0.3% for AGB.

Compared to RYGB, ≤30 days wound infection: AGB had lower risk (RD: -6.3%). >30 days stenosis: AGB had lower risk (RD: -15%). >30 days hernia: AGB had lower risk (RD: -4.5%). >30 days slippage/dilatation: AGB had higher risk (RD: 6.1%).

Overall complication rates: 17% in RCTs and 9.8% in OBSs. Procedure-specific complication rates: 21% in RCTs and 12% in OBSs for GB; 13% in RCTs and 7.8% in OBSs for AGB.

Reoperation outcomes

Not available. Combining all studies, 1.6% for RYGB; 7.7% for BPD.

Compared to RYGB, AGB had more late conversions/ reversal surgeries (32%)

Overall reoperation rates: 7.0% for RCTs and 5.8% in OBSs. Procedure-specific complication rates: 2.6% in RCTs and 5.3% in OBSs for GB; 12.2% in RCTs and 7.0% in OBSs for AGB.


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Weight loss outcomes

Time points: comorbidity outcome time point for which comorbidities were assessed %EWL: 61.2% for all patients; 47.5% for patients who underwent AGB; 61.6% for GB; 70.1% for BPD or DS. ∆BMI: -14.2 kg/m2 for all patients; -10.43 kg/m2 for AGB; -16.7 kg/m2 for GB; -17.99 kg/m2 for BPD or DS.

Time points: 1 year and ≥3 years after surgery ∆weight at 1 year: -30.19 kg for AGB; -43.46 kg for RYGB; -51.93 kg for BPD in all studies. ∆weight at ≥3 years: -34.77 for AGB; -41.46 kg for RYGB; -53.1 kg for BPD in all studies.

Time points: 1 year, 2 year, and 3-5 years after surgery ∆BMI at 1 year: Compared with RYGB, AGB had lower BMI loss by 6.5 kg/m2; standard care yielded lower BMI loss by 9.0 kg/m2. ∆BMI at 2 year: Compared with RYGB, AGB had lower BMI loss by 8.0 kg/m2; VBG had lower BMI loss by 4.1 kg/m2. ∆BMI at 3-5 years: Compared with RYGB, AGB had lower BMI loss by 7.7 kg/m2.

Time points: 1-5 years after surgery %EWL at 1 year: 59.8% in RCTs and 46.2% in OBSs for all patients; 72.3% in RCTs and 63.3% in OBSs for GB; 33.4% in RCTs and 34.4% in OBSs for AGB. %EWL at 2 year: 70.6% in RCTs and 64.0% in OBSs for all patients; 74.4% in RCTs and 80.1% in OBSs for GB; 53.6% in RCTs and 52.3% in OBSs for AGB. %EWL at 3 year: 56.7% in RCTs and 66.9% in OBSs for all patients; 76.4% in OBSs for GB; 56.7% in RCTs and 58.3% in OBSs for AGB. %EWL at 4 year: 74.8% in OBSs for all patients; 76.4% in OBSs for GB; 74.9% in OBSs for AGB. %EWL at 5 year: 41.6% in RCTs and 62.2% in OBSs for all patients; 64.9% in OBSs for GB; 41.6% in RCTs and 57.2% in OBSs for AGB. ∆BMI at 1 year: -13.5 kg/m2 in RCTs and -11.8 kg/m2 in OBSs for all patients; -14.5 kg/m2 in RCTs and -14.3 kg/m2 in OBSs for GB; -10.5 kg/m2 in RCTs and -7.7 kg/m2 in OBSs for AGB. ∆BMI <1 year: Compared with LRYGB, AGB and Control had lower BMI loss by 3.6 and 3.7 kg/m2, respectively.


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∆BMI at 2 year: -13.2 kg/m2 in RCTs and -11.8 kg/m2 in OBSs for all patients; -14.5 kg/m2 in RCTs and -12.9 kg/m2 in OBSs for GB; -11.3 kg/m2 in RCTs and -8.8 kg/m2 in OBSs for AGB. ∆BMI at 3 year: -9.2 kg/m2 in RCTs and -15.5 kg/m2 in OBSs for all patients; -16.8 kg/m2 in OBSs for GB; -9.2 kg/m2 in RCTs and -11.4 kg/m2 in OBSs for AGB. 1≤∆BMI<3 years: Compared with LRYGB, AGB, VBG, and Control had lower BMI loss by 6.4. 2-3, and 11.3 kg/m2, respectively. ∆BMI at 4 year: -17 kg/m2 in OBSs for all patients; -17.9 kg/m2 in OBSs for GB; -6.2 kg/m2 in OBSs for AGB. ∆BMI at 5 year: -11.4 kg/m2 in RCTs and -14.3 kg/m2 in OBSs for all patients; -16.0 kg/m2 in OBSs for GB; -11.4 kg/m2 in RCTs and -12.4 kg/m2 in OBSs for AGB. ∆BMI ≥3 years: Compared with LRYGB, AGB and Control had lower BMI loss by 20.2 and 30.6 kg/m2, respectively.

Contents in the table are for the purpose of comparison and do not reflect the full set of results. RCT: randomized controlled trial; OBS: observational studies; RE: random-effects; MTC: mixed treatment comparison; %EWL: percentage of excess weight loss; ∆BMI: change in body mass index; kg: kilogram; m: meter; GB: gastric bypass; BPD: biliopancreatic diversion; DS: duodenal switch; RYGB: Roux-en-Y Gastric Bypass; VBG: vertical banded gastroplasty.


supplementary online content · 2 eappendix authors: su-hsin chang phd1, carolyn r.t. stoll mph,...

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