sglt2 inhibitor -a boon in uncontrolled dm
TRANSCRIPT
A case of T2DM who is uncontrolled on Insulin Managed with Dapagliflozin add on to Insulin
Dr NIRMAL JAISWAL MD(med)Consultant Physician & ICU Director
Suretech Hospital Nagpur – India
Clinical Presentation:
A 52-year-old obese man
8- year history of type 2 diabetes
Generalized malaise and loss of appetite
since 2 weeks
Medical History:
Recently struggling to achieve glycemic
targets
weight gain over the past 5 years.
History suggestive of episodes of hypoglycemia
Family History:
Diabetes mellitus,
Hypertension
Case Presentation
Clinical Presentation:
High grade fever X 5 Days
Increasing breathlessness 3 days
Cough with expectoration X 5days
Case Presentation
Past history
Hypertensive and
dyslipidemic since past 3
years
Medication History
Tab Metformin 1500 mg BD + Inj Insulin
Premix 70/30 35 IU BD
Tab Lisinopril 10 mg OD for hypertension
Tab Atorvastatin 10 mg OD for dyslipidemia
Family History:
Mother was diabetic and hypertensive
The patient does not follow any specific diet. he rarely exercises due to fatigue and lack of energy
Case Presentation
General Examination:
• Obese,Weight: 79 Kg; Height: 162 cm; BMI: 30.1 Kg/m2; Waist circumference: 89 cm
• Fever:101 PR: 70/min , BP: 140/90 mmHg RR: 30 breaths /min ; Temperature: 100° F
Systemic Examination:
•RS: Crepts and TBB at base rt LL.•P/A: No hepatomegaly, No Spleenomegaly. Bowel sounds heard.•CVS: S1 and S2 heard, No added sounds
On Examination
Clinical Investigations
No abnormality detected in electrocardiography
Parameters Values
Hemoglobin 11.1 g/dL
Fasting blood glucose 142 mg/dL
Postprandial blood glucose 296 mg/dL
HbA1c 8.9%
Serum creatinine 0.9 mg/dL
Blood urea nitrogen 17 mg/dL
Total cholesterol 275 mg/dL
Low density lipoprotein-cholesterol 189 mg/dL
High-density lipoprotein-cholesterol 35 mg/dL
Triglycerides 255 mg/dL
Serum electrolytes Normal
eGFR 75 mL/min/1.73 m2
CBC : 11,34,23400LFT : NAD
X ray chest
Diagnosis• Rt lower lobe pneumonia in a case of Uncontrolled diabetes,
uncontrolled dyslipidemia, hypertension, and obesity
Management
• Inj Amoxy-clav + IV clarithro • What should be the choice of therapy for controlling DM in this
case scenario?
Diagnosis and Management Plan
Many good drugs are available but they have some limitation particularly – in CKD,derranged LFT, obesity or lead to weight gain
Choose A Safe drug which will help in preservation of organs in a long run which is a ultimate goal of ours
Limitations with current oral glucose-lowering agentsDo newer agents address these limitations??
Fonseca, V., et al. Diabetes Obes Metab. 2011 Apr 11; DeFronzo RA. Ann Intern Med. 1999;131:281–303;UKPDS. Lancet. 1998; 352:837–853; Aschner P, et al. Diabetes Care.2006;29(12):2632-7;ADA and EASD Consensus statement. Diabetes Care. 2009;32:193–203; Nesto RW, et al. Circulation 2003;108:2941–2948;Matthaei S, et al. Endocrine Reviews. 2000;21:585–618; Raptis SA & Dimitriadis GD. J Exp Clin Endocrinol. 2001;109:S265–S287.
Drug/Limitations
HYPO-GLYCEMIA
WEIGHT GAIN
CV RISK GI SIDE EFFECTS
RENAL MONITORING & DOSE ADJUSTMENT
DRUG-DRUG INTERACTIONS
HEPATIC MONITORING & DOSE ADJUSTMENT
BP REDUCTION
METFORMIN
SUS
GLINIDES
TZDs
GLP-1 RECEPTOR AGONISTS
INSULIN
DPP-4 I
AGIS
SGLT 2 INHIBITORSNewer agents
Favourable
Judicious use
Dapagliflozin as add-on to insulin (± OADs): Significant reductions in HbA1c sustained over 2 years1
Dapagliflozin is not indicated for the management of obesity.3 Weight change was a secondary endpoint in clinical trials.3,4
A multicentre, randomised, double-blind, placebo-controlled, parallel-group, 24-week study in patients with Type 2 diabetes with inadequate glycaemic control (HbA1c 7.5–10.5%) on a stable dose of insulin ± up to two OADs. Primary endpoint: HbA1c reduction at 24 weeks.1 Data are adjusted mean change from baseline estimated from a mixed model.1. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36; 2. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 3. Dapagliflozin. Summary of product characteristics, 2014; 4. Bailey CJ, et al. Lancet 2010;375:2223–33.
Dapagliflozin also offers…
additional benefit of weight loss without the
need for increased insulin
dosing
At 24 weeks, dapagliflozin was associated with HbA1c reductions of –0.96% versus –0.39% with placebo (p<0.001)2
Dapagliflozin as add-on to insulin (± OADs): Significant weight loss sustained over 2 years1
Dapagliflozin is not indicated for the management of obesity.2 Weight change was a secondary endpoint in clinical trials.2,3
A multicentre, randomised, double-blind, placebo-controlled, parallel-group, 24-week study in patients with Type 2 diabetes with inadequate glycaemic control (HbA1c 7.5–10.5%) on a stable dose of insulin ± up to two OADs. Primary endpoint: HbA1c reduction at 24 weeks. Data are adjusted mean change from baseline estimated from a mixed model. 1. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36; 2. Dapagliflozin. Summary of product characteristics, 2014; 3. Bailey CJ, et al. Lancet 2010;375:2223–33.
Reduction in Body weight by 3.33 Kgs
Dapagliflozin as add-on to insulin (± OADs): Reduction in Insulin requirement
IU, International units.1. Wilding JPH, et al. Ann Intern Med 2012;156:405–15; 2. Wilding JP, et al. Diabetes Obes Metab 2014;16:124–36.
Reduction in Insulin requirement > 18 U
Reduction in albuminuria with Dapagliflozin in Patients With Type 2 Diabetes and Moderate Renal Impairment
CI=confidence interval; DAPA=dapagliflozin; PBO=placebo. Sjöström CD et al. World Congress of Nephrology. March 13-17, 2015; Cape Town, South Africa. Poster SAT-461. T2D=type 2 diabetes; CKD=chronic kidney disease;SGLT=sodium-glucose cotransporter; eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate; UACR=urine albumin:creatinine ratio.Kohan DE et al. Kidney Int. 2014;85:962-971. Yale JF et al. Diabetes Obes Metab. 2013;15:463-473. Barnett AH et al. Lancet Diabetes Endocrinol.
2014;doi:10.1016/S22138587(13)70208-0. Gilbert RE. Kidney Int. 2013; doi:10.1038/ki.2013.451
The reduction in interglomerular pressure induced by SGLT2 inhibitors may provide benefits to patients with CKD
Dapagliflozin demonstrates potential nephroprotective effects in combination with renin-angiotensin system blockade, as significant reductions in UACR over 50 weeks in patients with T2D and moderate renal function were observed
UACR: Urine Albumin Creatinine Ratio
Dapagliflozin in High risk population
SGLT2i & Diabetic Nephropathy
Image used only for academic purposes SGLT2: Sodium Glucose Co TransporterDapa= Dapagliflozin. David Z.I. Cherney et al. Circulation. 2014;129:587-597CI=confidence interval; UACR=urine albumin: creatinine ratio; DAPA=dapagliflozin; PBO=placebo. Sjöström CD et al. World Congress of Nephrology. March 13-17, 2015; Cape Town, South Africa. Poster SAT-461. T2D=type 2 diabetes; CKD=chronic kidney disease;SGLT=sodium-glucose cotransporter; eGFR=estimated glomerular filtration rate; GFR=glomerular filtration rate; UACR=urine albumin:creatinine ratio. Kohan DE et al. Kidney Int. 2014;85:962-971. Yale JF et al. Diabetes Obes Metab. 2013;15:463-473. Barnett AH et al. Lancet Diabetes Endocrinol. 2014;doi:10.1016/S2213-8587(13)70208-0. Gilbert RE. Kidney Int. 2013; doi:10.1038/ki.2013.451
PossibleNephroprotection
Patient Populations where I would prefer other OADs
• Type 1 diabetes.
• Patients >75 years
• Patients with eGFR <45mL/min
• Pregnancy and Nursing woman
• Patients with Recurrent UTI / GUI
• Patients with history of volume depletion, dehydration
Views expressed are of the speaker.
Cefalu, et al. ADA 2012; Leiter et al ADA 2012.
• Due to increasing weight gain and hypoglycemic episodes, Dapagliflozin was added while Insulin dose was reduced to 55 IU (25% reduction in dose )*. Metformin was continued.
• Lifestyle intervention program which focused on low-fat diet and regular exercise was devised and the patient was counseled to adopt the same.
• Dosage of statins was increased to control lipid parameters.
• Self-monitoring of diabetes was encouraged to achieve better results and regular monitoring of blood pressure was advised.
Management
At 6 months
• Patient’s weight had reduced further 1.5 kg and her lipid parameters were approaching normal levels.• HbA1c 7.5%, not reporting episodes of hypoglycemia
Follow-Up
At 3 months:
• Weight loss of about 2.5 kg• HbA1c: 7.9% ; FBS:128 mg/dL; PPBS: 208 mg/dL• SBP and DBP decreased by 4mmHg and 2mmHg respectively.• Lipid parameters improved.• Advised to continue with same medications with no need to increase Insulin dose• Lifestyle modifications reinforced
Take home massage
• SGLT2 inhibitors can be better choice
who has normal renal function (eGFR- >45) along with insulins or OHA in case of uncontrolled hyperglycemia in type 2 DM
