A debate showing why SGLT2 inhibitors have not have a major advantage over DPP4 inhibitors as the next add on drug after Metformin in the management of Type 2 Diabetes

1. 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 Majumdar
MD, FRCP, MACE(USA)
Consultant Endocrinologist
Faculty, Certificate Course in Evidence Based Diabetes Management
Examiner MRCP(Ireland) Clinicals
Contributory Author , Diapedia- the online Textbook of Diabetes of the European Association for the
Study of Diabetes(EASD)

2. Lessons from History
“A false fact
spoken one
hundred times
becomes the
truth”

3. What do the latest guideline say ?

4. What do the latest guideline say ?
ANAny evidence suggesting superiority of
SGLT2 inhibitors over DPP4 inhibitors?

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

6. DPP4 inhibitors vs SGLT2 inhibitors

7. 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

9. 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.

11. 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 ?

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

14. 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

15. Position of DPP4 inhibitors in the
Type II DM algorithm globally

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

17. In the end..... When choosing your
partner
Do you rely on somebody..... WHOM YOU HAVE
KNOWN FOR SEVEN YEARS
OR
Choose somebody, whom you have known for A
FEW MONTHS ONLY?

18. A Final Caveat ...... Though
UNITED WE STAND—DIVIDED WE FALL

19. Thank you