Abstract
BackgroundIt is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs.MethodsPooled 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).ResultsIn 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).ConclusionsAnalysis of pooled data from 20 clinical trials in patients with T2DM suggests that saxagliptin is not associated with an increased CV risk.
Highlights
Cardiovascular (CV) disease is the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM) [1]
Results from large outcome trials of saxagliptin in patients with prior CV disease or multiple CV risk factors (SAVOR) [25] and alogliptin in patients after acute coronary syndrome (EXAMINE) have recently been published [26] and have shown that saxagliptin and alogliptin do not increase or decrease major adverse CV events (MACE). In contrast to those trials in patients with T2DM and high CV risk, the current analysis evaluated MACE and its individual component events of CV death, myocardial infarction (MI) and stroke, as well as heart failure, with saxagliptin in the general population of patients with T2DM that participated in the saxagliptin clinical development program
Patient demographics and clinical characteristics In the 20-study pool, demographic and clinical characteristics were similar between the saxagliptin (n = 5701) and control (n = 3455) groups (Table 2)
Summary
Cardiovascular (CV) disease is the leading cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM) [1]. Epidemiologic studies suggest that hyperglycemia is associated with adverse CV events [3-5], the effects of intensive glycemic control on CV outcomes in interventional studies are not clear [6-8]. In some studies and with some antihyperglycemic drugs, a tendency toward an increased risk for CV events has Because of the uncertainty surrounding glycemic control and CV events and the association of increased CV events with some antihyperglycemic drugs, in 2008 the US Food and Drug Administration recommended that CV safety be assessed as a component of the clinical development program of new antihyperglycemic drugs [13]. Saxagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor approved as an adjunct to diet and exercise to improve glycemic control in adults with T2DM [14]. It is of interest to assess the CV safety of DPP-4 inhibitors. It is important to establish the cardiovascular (CV) safety profile of novel antidiabetic drugs
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