clinical dilemmas in obesity management robert b. baron md ms professor and associate dean ucsf...
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CLINICAL DILEMMAS IN OBESITY CLINICAL DILEMMAS IN OBESITY MANAGEMENTMANAGEMENT
Robert B. Baron MD MSRobert B. Baron MD MS
Professor and Associate Dean Professor and Associate Dean
UCSF School of MedicineUCSF School of Medicine
Declaration of full disclosure: No conflict of interest
Case 1Case 1
50 year old woman, in good health, no history of cigarettes, in for check up. BMI 29.
Should you tell her she is overweight?
What further assessment and treatment should you begin?
CLASSIFICATION OF OVERWEIGHT AND OBESITY BY BMI
Obesity Class BMI (kg/m2)
Underweight <18.5
Normal 18.5 – 24.9
Overweight 25.0 – 29.9
Obesity I 30.0 – 34.9
II 35.0 – 39.9
Extreme Obesity III >40
Flegal, JAMA, 2005
BMI AND MORTALITY: BMI AND MORTALITY: OverallOverall
Combined NHANES I, II, and III data set
BMI 25-59 y 60-69 y ≥70 y
<18.5 1.38 2.30 1.6918.5-<25 1.00 1.00 1.0025 to <30 0.83 0.95 0.9130 to <35 1.20 1.13 1.03≥35 1.83 1.63 1.17
An Office-Based ApproachAn Office-Based Approach
Make the diagnosis (and communicate it)
Assess readiness for change
Prescribe diet and exercise
Consider medications and surgery
HEALTH PROFESSIONAL ADVICE AND WEIGHT LOSS
12,835 adults, BMI over 30 kg/m2, check-up in last year
Random-digit, population-based sample, 50 states
• 42% told by health professional to lose weight
Those told to lose weight more likely to report trying to lose weight: OR 2.79 (95% CI 2.53-3.08)
Gregg, Ann Int Med 2003
INTENTIONAL WEIGHT LOSS AND DEATH
Prospective CDC cohort study, 6391 adults, followed for 9 years
• Those reporting intentional weight loss had 24% reduction in mortality
• Those reporting unintentional weight loss had 31% higher mortality
• Those reporting attempted but unsuccessful weight loss also had 20% reduction in mortality
NCEP, JAMA 2001
METABOLIC SYNDROMEMETABOLIC SYNDROME
Fulfill 3 or more criteria:
Waist: men > 102 cm ( > 40 in); women > 88 cm ( > 35 in)
HDL: men < 40; women < 50
Triglycerides: ≥150 mg/dl
BP: ≥130/85 (or use of medications)
Fasting glucose: ≥110 mg/dl
ICD-9: 277.7
GOALS OF MANAGEMENT
Be as fit as possible at current weight
Prevent further weight gain
If successful at 1 and 2, begin weight loss
Case 2Case 2
50 year old woman, in good health, in for check up. BMI 32 with metabolic syndrome.
She says, “ I have to lose weight, and I am planning on doing that. I am about to try the South Beach diet.”
DIET THERAPYDIET THERAPY
• 48 RCT’S
• Average weight loss 8% over 3-12 months
Anderson, Am J Clin Nutr, 2001
VLCD’s vs LCD’s: VLCD’s vs LCD’s: Meta-analysis of 29 U.S. StudiesMeta-analysis of 29 U.S. Studies
• Weight loss studies with > two year f/u• 13 VLCDs, 14 LCDs • Mostly observational studies (few RCT’s)
Weight loss (as % of initial weight):
1y 2y 3y 4y 5y
LCDs 7.2 4.2 3.5 2.8 2.0
VLCDs 16.1 9.7 7.8 7.0 6.2
Dansinger, JAMA 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE
Intention to treat at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 2.1 3.3 3.0 3.2Completers (%) 53 50 65 65
Completers at 1 year Atkins Ornish WW Zone
Wt Loss (kg) 3.9 6.6 4.6 4.9
160 patients, randomly assigned
Dansinger, JAMA, 2005
COMPARISON OF ATKINS, ORNISH, COMPARISON OF ATKINS, ORNISH, WEIGHT WATCHERS, AND ZONEWEIGHT WATCHERS, AND ZONE
Each group: 25% lost 5%, 10% lost 10% of initial weight
Each diet reduced LDL/HDL by 10%
No significant effects on BP or glucose
Weight loss associated with adherence, but not diet type
CRP and insulin reductions associated with weight loss, but not diet
DIET APPROACHESDIET APPROACHES Diets
low cal (low fat, low carbohydrate), meal replacement
Commercial programsWeight Watchers™, Jenny Craig™, TOPS™, Overeaters Anonymous™, Nutrisystem.com,™ Shapedown,™ The Solution™
Internet programs (by RDs)Fitday.com, Dietwatch.com, Cyberdiet.com, eDiets.com, Shapeup.org
Wei, JAMA 1999
FITNESS AND MORTALITYFITNESS AND MORTALITYAerobics Center Longitudinal StudyAerobics Center Longitudinal Study
CV death (RR) normal overweight obese
Fit 1.0 1.5 1.6Not fit 3.1 4.5 5.0
Total death (RR) normal overweight obese
Fit 1.0 1.1 1.1Not fit 2.2 2.5 3.1
25,714 men, 44 years old, 14 year observational study
Hu FB, NEJM 2004
FITNESS AND OBESITYFITNESS AND OBESITYNurses Health StudyNurses Health Study
Total death (RR)
normal overweight Active 1.00 1.91
Not active 1.55 2.42
116,564 women, 24 year observational study
Wing and Hill, Ann Rev Nutr, 2001
SUCCESSFUL WEIGHT LOSS SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE
3000 subjects in National Weight Control Registry: 30-lb weight loss for 1-year
Average weight loss 30kg (10 BMI units less), average weight maintenance 5.5 years
45 years old, 80% women, 97% Caucasian
46% overweight as child, 46% one parent obese, 27% both parents
Wing and Hill, Ann Rev Nutr, 2001
SUCCESSFUL WEIGHT LOSS SUCCESSFUL WEIGHT LOSS MAINTENANCEMAINTENANCE
• High levels of physical activity• Women 2545 kcal/week, men 3293 kcal/week • (1-hour moderate intensity per day• Only 9% report no physical activity
• Diet low in fat, high in carbohydrate• 1381 kcal day, 24% fat, 19% protein, 56% CHO• 4.87 meals or snacks/day• Fast food 0.74/week
• Regular self-monitoring of weight• 44% weigh once per day; 31% once per week
Case 3Case 3
46 year old woman, in good health, in for check up. BMI 42 with diabetes.
In 1996 she lost 20 pounds on phen-fen. She wants a new weight loss drug and a referral for weight loss surgery.
Glazer, Arch Int Med 2001
“LONG TERM” PHARMACOTHERAPY OF OBESITY
Review of all RCT’s more than 36 weeks published since 1960
Weight loss in excess of placebo:
% of initial kg’s
Phen-fen 11.0% 9.6 kg
Phentermine 8.1% 7.9 kg
Sibutramine 5.0% 4.3 kg
Orlistat 3.4% 3.4 kg
Dexfenfluramine 3.0% 2.5 Kg
Fluoxetine -0.4% -0.4 kg
Diethyproprion -1.5% -1.5 kg
Wadden, T. A. et al. N Engl J Med 2005;353:2111-2120
SIBUTRAMINE ALONE AND WITH LIFESTYLE MODIFICATION
OFF-LABEL USESertraline – SSRI
– More selective 5-HT uptake inhibitor– In Phase III trials now
Buproprion – NA re-uptake inhibitor– RCT of 327 obese pts, 24 weeks; – Wt. loss: 2% placebo vs. 5% in 300/400 mg
Topiramate – CA inhibitor– RCT in 385 obese pts; dose-ranging; 24 wks– Wt loss: -2.6% placebo vs. -5 to -6% w/drug
OTHER DRUGS OFF-LABEL Amantadine
Other SSRIs (fuvoxamine, venlafaxine, citalopram, others)
H2 blockers (cimetidine)
Metformin – Wt loss: -2 kg with drug vs. -0 kg with placebo vs. -4 kg with
lifestyle in DPP
Exenatide (Byetta) - Wt loss: -4-5 kg in open label study at 80+ weeks
Zonisamide – antiepileptic– Wt loss: -5.9 kg with drug vs. 0.9 kg with placebo
RIMONABANT (Acomplia™)
• 1,507 severely obese people, Europe, 2-years (2005)
rimonabant 7.3 kg loss
placebo 2.5 kg loss
• 3,040 obese people, US, 2-years (2004)
rimonabant 7.6 kg loss
placebo 2.3 kg loss
-10
-8
-6
-4
-2
0
Ch
ang
e F
rom
Bas
elin
e, k
g
0 12 24
36 52
Placebo
5 mg of Rimonabant
20 mg of Rimonabant
Weeks
Year 1 Body Weight
-10
-8
-6
-4
-2
0
Ch
ang
e F
rom
Bas
elin
e, k
g
52 60 76 92 104
Placebo/Placebo
20 mg rimonabant/Placebo
20 mg rimonabant/20 mg
Weeks
Year 2 Body Weight
8468
RIMONABANT (Acomplia™)Side Effects
Nausea: 13.7% with drug vs. 5.5% on placebo
Dizziness: double with drug
Diarrhea: double with drug
Depression: 2.8% vs. 1.6%
Drop outs: 19% with drug vs. 13% with placebo
PRINCIPLES OF DRUG THERAPYPRINCIPLES OF DRUG THERAPY
• NIH: BMI > 30 kg/m2 or 27 kg/m2 with co-morbidity (but in practice almost never)
• Motivated to begin structured exercise and low calorie diet
• Begin medications at completion of one month successful diet and exercise
• Continue medications only if additional weight loss achieved in first month with meds
Wouldn’t It Be Easier Just To Have Surgery?
0
20000
40000
60000
80000
100000
120000
No
. of
Pro
ce d
ure
s
Year
National Trends in Annual NumbersNational Trends in Annual Numbers of Bariatric Procedures, 1998-2003of Bariatric Procedures, 1998-2003
1998 1999 2000 2001 2002 2003
Data based on nationwide inpatient sampleProjection based on preliminary data from 12 states for 2003
Error bars indicate 95% confidence intervals
Who’s Getting Surgery?
Approved by most payers; cost effective
Recent review indicates more surgeries done in:
–women
–those with private insurance
–those living in wealthier zip codes
Santry HP et al JAMA 2005;294:1909
Types of Surgery
Restrictive• Horizontal Gastroplasties• Vertical Banded Gastroplasty (VGB)• Silastic Ring Vertical Gastroplasty (SRVG)• Adjustable Gastric Banding
Malabsorptive• Jejunoileal Bypass (JIB)• Biliopancreatic Diversion (BPD)• Duodenal Switch• Long Limb Gastric Bypass
Restrictive with Malabsorptive Component• Roux-en-Y Gastric Bypass (RYGPB)
Restrictive Procedures
VBGVBG Adjustable Gastric Banding Roux-en-Y GB
Buchwald, JAMA, 2004
BARIATRIC SURGERY META-ANALYSIS
Review of bariatric surgery (136 studies), 1990-2003, 22,092 patients
weight loss (kgs) BMI decrease % excess weight
loss
Total -39.71 -14.20 -61.23
Gastric Banding -28.64 -10.43 -47.45
Gastric Bypass -43.48 -16.70 -61.56
Gastroplasty -39.82 -14.20 -68.17
Biliopancreatic diversion
or duodenal switch -46.39 -17.99 -70.12
Resolution of Comorbidities
0
10
20
30
40
50
60
70
80
90
100
Diabetes Hyperlipidemia HTN Sleep apnea
Band
VBG
GBP
D Switch
% R
esol
utio
nC
omor
bidi
tyBariatric Surgery – A Systematic Review and Meta-analysis
Buchwald H. et al.JAMA. 2004; 292(14):1724-37
Buchwald, JAMA, 2004
BARIATRIC SURGERY META-ANALYSIS
Review of bariatric surgery (136 studies), 22,092 patients
Operative Mortality
Gastric Banding 0.1%
Gastric Bypass 0.5%
Gastroplasty 0.1%
Biliopancreatic diversion
or duodenal switch 1.1%
.
Flum, D. R. et al. JAMA 2005;294:1903-1908.
Mortality Rate After Bariatric Surgery
Flum, D. R. et al. JAMA 2005;294:1903-1908.
Survival After Bariatric Surgery by Age Group
Klein, NEJM 2004
LACK OF METABOLIC EFFECTS OF LIPOSUCTION
• 15 women, before and after liposuction (8 with normal glucose tolerance, 7 with diabetes)
• Weight loss: 9.1 kg (NLs) and 10.5kg (DM)
• No change in insulin sensitivity of muscle, liver, or adipose tissue
• No change in C-reactive protein, IL-6, TNF
alpha or adiponectin
• No change BP, glucose, insulin, lipids
The Magic Formula
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