Abstract 11105: Cardiovascular Safety of the SGLT2 Inhibitor Dapagliflozin: Meta-Analysis With >6000 Patient-Years Exposure
Cardiovascular disease (CVD) risk is increased in patients with type 2 diabetes mellitus (T2DM). Dapagliflozin (DAPA), a selective SGLT2 inhibitor, is approved treatment for T2DM in several countries. DAPA promotes renal glucose excretion and mild osmotic diuresis, thereby reducing hyperglycemia, weight, and blood pressure. Data from 21 clinical studies, including 2 that exclusively enrolled patients with a history of CVD, were included in a prespecified meta-analysis (n=9339) to assess the CV safety of dapagliflozin (2.5 to >10 mg/d; n=5936) vs comparators (COMP; placebo or active, n=3403). Potential CV end points were systematically identified from investigator reports of adverse events based on a prespecified list of terms, and were independently adjudicated in a blinded manner. The prespecified primary end point was a composite of time to CV death, myocardial infarction (MI), stroke or hospitalization for unstable angina. The secondary end point included the primary end point plus unplanned coronary revascularization and hospitalization for heart failure. Baseline characteristics were similar for DAPA and COMP groups (mean age=56.9, 58.1 years (y); age ≥65 y=24.0%, 28.8%; body mass index=31.3, 31.6 kg/m2; T2DM duration=6.9, 7.6 y, respectively) and reflected CV risk in the general T2DM population (history of CVD: DAPA: 31.3% and COMP: 39.9%). Total patient exposures with respect to the primary end point were 6514 y in the DAPA group and 3777 y in the COMP group. For this end point, 176 events occurred (DAPA: 95; COMP: 81) and the incidence rates/1000 subject y were 14.6 for DAPA vs 21.5 for COMP. The estimated hazard ratio (HR) using a Cox proportional hazards method was 0.787 (95% CI: 0.579, 1.070). Analyses of the secondary end point (HR: 0.758; 95% CI: 0.581, 0.988) and of an ad-hoc major adverse CV events composite end point of CV death, MI and stroke (HR: 0.772; 95% CI: 0.543, 1.097) were consistent with the primary end point results. These results are comparable to findings from a previously reported shorter follow-up period. These findings suggest that there is no increase in CV risk associated with DAPA in an updated CV risk analysis that includes more patients and a substantial proportion of older patients (>20%) and patients with established CVD (>30%).
- © 2013 by American Heart Association, Inc.