Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials

Abstract

Background: It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs.

Methods: Pooled analyses were performed of 20 randomized controlled studies (N = 9156) of saxagliptin as monotherapy or add-on therapy in patients with type 2 diabetes mellitus (T2DM) as well as a subset of 11 saxagliptin + metformin studies. Adjudicated major adverse CV events (MACE; CV death, myocardial infarction [MI], and stroke) and investigator-reported heart failure were assessed, and incidence rates (IRs; events/100 patient-years) and IR ratios (IRRs; saxagliptin/control) were calculated (Mantel-Haenszel method).

Results: In pooled datasets, the IR point estimates for MACE and individual components of CV death, MI, and stroke favored saxagliptin, but the 95% CI included 1. IRR (95% CI) for MACE in the 20-study pool was 0.74 (0.45, 1.25). The Cox proportional hazard ratio (95% CI) was 0.75 (0.46, 1.21), suggesting no increased risk of MACE in the 20-study pool. In the 11-study saxagliptin + metformin pool, the IRR for MACE was 0.93 (0.44, 1.99). In the 20-study pool, the IRR for heart failure was 0.55 (0.27, 1.12).

Conclusions: Analysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk.

Figure 1

Incidence rate ratios for saxagliptin vs control (point estimates and 95% CI) for MACE in the 20-study pool, the saxagliptin 2.5- and 5-mg subanalysis, and the add-on to metformin study pool. Numbers in parentheses are total patient-years of exposure (the time up to an event or censoring). IRR = incidence rate ratio; MACE = major adverse cardiovascular events; MET = metformin; SAXA = saxagliptin.

Figure 2

Incidence rate ratios for saxagliptin vs control (point estimates and 95% CI) for CV death, myocardial infarction, stroke, and heart failure in the 20-study pool. Numbers in parentheses are total patient-years of exposure (the time up to an event or censoring). CV = cardiovascular; IRR = incidence rate ratio; MACE = major adverse cardiovascular events; SAXA = saxagliptin.

Figure 3

Incidence rate ratios for saxagliptin vs control (point estimates and 95% CI) for CV death, myocardial infarction, and stroke in the add-on to metformin study pool. Numbers in parentheses are total patient-years of exposure (the time up to an event or censoring). CV = cardiovascular; IRR = incidence rate ratio; SAXA = saxagliptin.