Dpp4i vs sglt2 inhibitors against the motion
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Transcript of Dpp4i vs sglt2 inhibitors against the motion
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In the Management of Type II Diabetes SGLT2 inhibitors are preferable to DPP4 inhibitors as
the next add on drug after Metformin AGAINST THE MOTION
Dr Sujoy MajumdarMD, FRCP, MACE(USA)
Consultant EndocrinologistFaculty, Certificate Course in Evidence Based Diabetes Management
Examiner MRCP(Ireland) ClinicalsContributory Author , Diapedia- the online Textbook of Diabetes of the European Association for the Study of
Diabetes(EASD)
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Lessons from History
“A false fact spoken one hundred times becomes the truth”
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What do the latest guideline say ?
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What do the latest guideline say ?
ANAny evidence suggesting superiority of SGLT2 inhibitors over DPP4 inhibitors?
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Hba1c reduction with different glucose lowering therapy (added to Metformin)
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DPP4 inhibitors vs SGLT2 inhibitors
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So.... What is the actual story ?
DPP4 inhibitors• ↓Hba1c 0.6-0.82 %• Weight neutral• Minimal risk of hypoglycemia• No additional risk of UTI/
Genital mycosis• Can be used with dose
modification upto eGFR <15• No reported DKA• Reduces glucagon• No dyselectrolytemia/
hypotension
SGLT2 inhibitors• ↓Hba1c 0.43-0.67%• Weight loss• Minimal risk of hypoglycemia• 3-43% increased risk of UTI• 3-5 times increased risk of genital
mycoses• Can’t be used below eGFR 30
(Empa) or<45 (Cana), < 60 (Dapa)• Around 100 reported cases of
euglycemic DKA• Increases glucagon• Significant dyselectrolytemia/
hypotension in some cases
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Ideal Candidates for SGLT2 inhibitors
• Type 2 Diabetic Patients with good Renal Function.
• Hypertensive Diabetic Patients.
• Overweight and Obese Type 2 Diabetic Patients.
• Type 2 Diabetic Patient with frequent hypoglycaemic episodes and/or weight gain with existing therapy particularly on SUs.
• Type 2 Diabetic patients experiencing therapy related limiting adverse events. For example GI side effects with GLP-1 analogs or with AGI use.
• Type 2 Diabetic patient with not too poor glycaemic control while on monotherapy or combination therapy.
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CV protection • Just as “ One swallow doesn’t make a
summer”...... One Empa Reg doesn’t make SGLT2 inhibitors the molecules of choice !
Key inclusion criteria– Adults with type 2 diabetes– BMI ≤45 kg/m2 – HbA1c 7–10%* – Established cardiovascular disease
Prior myocardial infarction, coronary artery disease, stroke, unstable angina or occlusive peripheral arterial disease
Key exclusion criteria– eGFR <30 mL/min/1.73m2 (MDRD)
CAN WE EXTRAPOLATE THAT BENEFIT TO PATIENTS WITH NO CV DISEASE ?
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CV outcome trials TECOS (on Sitagliptin),SAVOR-TIMI (on Saxagliptin) and EXAMINE (on Alogliptin) demonstrated neutral CV risk and no CV benefits
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SAVOR-TIMI 53 EXAMINE TECOS
Primary Composite CV End-Points
HR 1.00 [CI; 0.89-1.12]
HR 0.96 [C.I- UL: 1.16] HR 0.98 [CI; 0.88-1.09]
Heart Failure HR 1.27 [CI; 1.07-1.51]FDA-Reanalysis:HR 1.16; [CI; 1.03-1.30]
HR 1.19 [CI; 0.89-1.57]FDA-Reanalysis:HR 0.98 [CI; 0.84-1.13]
HR 1.00 [CI; 0.83-1.20]FDA-Reanalysis:HR 1.02 [CI; 0.90-1.15]
All-cause Mortality (7-days death)
MACE: Risk
HR 1.23 [CI; 1.02-1.48]
Higher risk of MACE in:• Smokers, DM duration >10
yrs., Metformin non-users, Insulin users, mod-severe renal insufficiency.
• Patients from US & Canada
Hypoglycemia HR 1.16 [CI; I.08-1.25]
6.7% (A) VS. 6.5% (P)
Adverse effects Serum Creatinine Elevation:3.2% (S) VS. 3.0% (P) NS
X 3-times elevated AST
NO INCREASED RISK OF PANCREATITIS/PANCREATIC CARCINOMA
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Position of DPP4 inhibitors in the Type II DM algorithm globally
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Market Position of DPP4 inhibitors in the management of Type II DM
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In the end..... When choosing your partner
Do you rely on somebody..... WHOM YOU HAVE KNOWN FOR SEVEN YEARS
ORChoose somebody, whom you have known for A
FEW MONTHS ONLY?
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A Final Caveat ...... ThoughUNITED WE STAND—DIVIDED WE FALL
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Thank you