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)

Lessons from History

“A false fact spoken one hundred times becomes the truth”

What do the latest guideline say ?

What do the latest guideline say ?

ANAny evidence suggesting superiority of SGLT2 inhibitors over DPP4 inhibitors?

Hba1c reduction with different glucose lowering therapy (added to Metformin)

DPP4 inhibitors vs SGLT2 inhibitors

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

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.

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 ?

CV outcome trials TECOS (on Sitagliptin),SAVOR-TIMI (on Saxagliptin) and EXAMINE (on Alogliptin) demonstrated neutral CV risk and no CV benefits

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

Position of DPP4 inhibitors in the Type II DM algorithm globally

Market Position of DPP4 inhibitors in the management of Type II DM

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?

A Final Caveat ...... ThoughUNITED WE STAND—DIVIDED WE FALL

Thank you