(33) Comparative Effectiveness of Sodium-Glucose Co-Transporter-2 Inhibitors Versus Dipeptidyl Peptidase-4 Inhibitors in Reducing Incidence of Stroke and Myocardial Infarction in Patients with Type 2 Diabetes

Publication Number: 707

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the incidence of cardiovascular endpoints in patients with type 2 diabetes. However, evidence regarding the cardiovascular benefits of SGLT2 inhibitors compared with other commonly used second-line antidiabetic drugs remains limited.

Objectives: To assess the comparative effectiveness of SGLT2 inhibitors vs. dipeptidyl peptidase-4 (DPP4) inhibitors in reducing the incidence of stroke and myocardial infarction (MI).

Methods: We conducted a new-user active comparator cohort study design using a U.S.-based commercial healthcare insurance database from 1 January 2015 to 30 June 2020. We included patients who: (a) initiated treatment with a SGLT2 inhibitor or DPP4 inhibitor; (b) had 12 months of continuous enrollment prior to treatment initiation (i.e., lookback period); (c) had a diagnosis of type 2 diabetes during lookback period; and (d) were 18 years or older at cohort entry. The main outcome was a composite of stroke and MI. Patients in the cohort were followed until the earliest of: treatment discontinuation, switch to the comparator drug, outcome, disenrollment from healthcare benefits, death, or end of study period. We adjusted for confounders via propensity score matching. We used Cox proportional-hazards regression with a robust variance estimator to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) while adjusting for calendar time. We stratified the primary analysis by individual outcomes.

Results: The matched cohort included 135,482 new users of SGLT2 inhibitors and 135,482 new users of DPP4 inhibitors. The incidence rates of the stroke-MI composite per 100 person-years were 2.6 and 3.0 for SGLT2 inhibitors and DPP4 inhibitors, respectively. In Cox proportional-hazards models, the use of SGLT2 inhibitors was associated with a lower rate of stroke or MI (adjusted HR (aHR), 0.93; 95% CI 0.88–0.98) compared to DPP4 inhibitors. The benefit of SGLT2 inhibitors vs. DPP4 inhibitors was evident for stroke (aHR, 0.82; 95% CI 0.71–0.95) but not myocardial infarction (aHR, 0.99; 95% CI 0.88–1.13).

Conclusions: Use of SGLT2 inhibitors was associated with a lower rate of a composite outcome of stroke or MI compared to DPP4 inhibitors. This finding appears to be driven by a lower incidence of stroke in persons taking SGLT2 inhibitors.