SGLT-2 inhibitors linked to lower risk of cardiac events compared with DPP-4 inhibitors

A retrospective study of Canadian and British patients with type 2 diabetes found lower rates of cardiovascular death among those taking sodium-glucose cotransporter-2 (SGLT-2) inhibitors than in matched patients who took dipeptidyl peptidase-4 (DPP-4) inhibitors.


In a recent study of patients with type 2 diabetes, use of sodium-glucose cotransporter-2 (SGLT-2) inhibitors was associated with a decreased risk of serious cardiovascular events compared with use of dipeptidyl peptidase-4 (DPP-4) inhibitors, with similar reductions observed across individual SGLT-2 inhibitors.

Investigators for the Canadian Network for Observational Drug Effect Studies conducted a retrospective cohort study using administrative health care databases from seven Canadian provinces and the U.K. They identified all adult patients who received an antidiabetic drug between Jan. 1, 2006, and June 30, 2018, then matched patients using SGLT-2 inhibitors (alone or in combination with other antidiabetic drugs) with those using DPP-4 inhibitors (alone or in combination with other antidiabetic drugs) based on time-conditional propensity score. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of myocardial infarction, ischemic stroke, or cardiovascular death. Secondary outcomes were the individual components of MACE, heart failure, and all-cause mortality. Results were published online on Sept. 23 by The BMJ.

From 270,902 users of SGLT-2 inhibitors and 632,114 users of DPP-4 inhibitors, 209,867 matched pairs were included in the study cohort. Among users of SGLT-2 inhibitors, 42.3% initiated canagliflozin, 30.7% initiated dapagliflozin, and 27.0% initiated empagliflozin at cohort entry. For the primary outcome of MACE, the mean duration of follow-up in the matched cohort was 0.9 year, with a total of 370,515 person-years of observation time. Compared with DPP-4 inhibitors, SGLT-2 inhibitors were associated with decreased risks of MACE (incidence rate, 11.4 vs. 16.5; hazard ratio [HR], 0.76 [95% CI, 0.69 to 0.84]), myocardial infarction (incidence rate, 5.1 vs. 6.4; HR, 0.82 [95% CI, 0.70 to 0.96]), cardiovascular death (incidence rate, 3.9 vs. 7.7; HR, 0.60 [95% CI, 0.54 to 0.67]), heart failure (incidence rate, 3.1 vs. 7.7; HR, 0.43 [95% CI, 0.37 to 0.51]), and all-cause mortality (incidence rate, 8.7 vs. 17.3; HR, 0.6; [95% CI, 0.54 to 0.67]). SGLT-2 inhibitors had more modest benefits for ischemic stroke (incidence rate, 2.6 vs. 3.5; HR, 0.85 [95% CI, 0.72 to 1.01]). Similar benefits for MACE were observed with canagliflozin (HR, 0.79; 95% CI, 0.66 to 0.94), dapagliflozin (HR, 0.73; 95% CI, 0.63 to 0.85), and empagliflozin (HR, 0.77; 95% CI, 0.68 to 0.87) and across patient subgroups defined by age, sex, past insulin use, and history of cardiovascular disease or heart failure. (All incidence rates are presented per 1,000 person-years.)

Limitations of the study include its observational design, potential residual or unmeasured confounding bias, and the possibility of misclassification of exposure, as data for prescriptions do not represent actual consumption, the authors noted. In addition, due to the short mean duration of follow-up, the results may be related to short-term hemodynamic effects of SGLT-2 inhibitors rather than disease-modifying benefits in the long term, they said.

“These findings suggest that SGLT2 inhibitors offer cardioprotective benefits among people with type 2 diabetes in a real world setting, although additional studies are needed to determine if these benefits persist long term,” the authors concluded.