SGLT2 inhibitors versus DPP4 inhibitors - comparing cardiovascular risk benefits

Last edited 10/2020 and last reviewed 01/2021

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) are glucose lowering drugs used in the treatment of Type 2 Diabetes Mellitus (T2DM).

  • CV outcome trials showed that SGLT2i reduced the risk of major adverse CV events in patients with T2DM and atherosclerotic CVD (ASCVD) or CKD [1,2]
  • in addition, SGLT2i also reduced the risk of hospitalization for HF in patients with T2DM with and without ASCVD [2,3,4]
  • DPP-4i have shown no effect on ischemic events or CV death and the DPP-4is have shown no effect on hospitalization for HF [5]

Pleiotropic effects of SGLT2is: head-to-head comparisons with DPP4-is in T2DM:

  • study evidence (6) has shown that SGLT2i had glucose-lowering effects comparable to those of DPP-4i but more favourable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients' cardiometabolic disease risks

Comparing CV risk benefits of SGLT2is versus DPP-4is:

A comparative cohort analysis from the CVD-REAL 2 study used data from de-identified health records from 13 countries (Australia, Canada, Denmark, Germany, Israel, Japan, Norway, Singapore, South Korea, Spain, Sweden, Taiwan, and the USA). These data were used to assess the risk of CV events and death in adults with T2DM newly initiated on SGLT2i compared with those newly initiated on DPP-4i (7)

  • comparative cohort study showed that initiation of SGLT2i versus DPP-4i in adults with T2DM was associated with substantially lower risks of hospitalization for HF and all-cause death and with modestly, but significantly lower risks of MI and stroke in clinical practice.

Adding either SGLT2i or DPP-4is to patients with inadequate glycaemic control on insulin:

  • study evidence showed SGLT2is achieved better glycaemic control and greater weight reduction than DPP4 inhibitors without increasing the risk of hypoglycaemia in patients with T2DM that is inadequately controlled with insulin (8)


  • American Diabetes Association. 10. Cardiovascular disease and risk management: Standards of Medical Care in Diabetes - 2019. Diabetes Care 2019; 42 (suppl 1):S103-23.
  • Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373: 2117-28.
  • Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377: 644-57.
  • Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380: 347-57.
  • Sinha B, Ghosal S. Meta-analyses of the effects of DPP-4 inhibitors, SGLT2 inhibitors and GLP1 receptor analogues on cardiovascular death, myocardial infarction, stroke and hospitalization for heart failure. Diabetes Res Clin Pract 2019; 150: 8-16.
  • Shao et al.Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes
    patients Cardiovasc Diabetol (2020) 19:17
  • Khosaka S et al. Risk of cardiovascular events and death associated with initiation of SGLT2 inhibitors compared with DPP-4 inhibitors: an analysis from the CVD-REAL 2 multinational cohort study Lancet Diabetes Endocrinol 2020; 8; 606-15
  • Min SE et al. Comparison between SGLT2 inhibitors and DPP4 inhibitors added to insulin therapy in type 2 diabetes: a systematic review with indirect comparison meta-analysis. Diabetes Metab Res Rev 2017; 33: e2818.