201. Assessment of the cardiovascular safety of saxagliptin in patients with type 2 diabetes mellitus: pooled analysis of 20 clinical trials
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Nayyar Iqbal, Mark Donovan, Artist Parker, Robert Frederich, and Boaz Hirshberg
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medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Adamantane ,Dipeptidyl peptidase-4 inhibitor ,Saxagliptin ,chemistry.chemical_compound ,Diabetes mellitus ,Internal medicine ,Type 2 diabetes mellitus ,Medicine ,Humans ,In patient ,cardiovascular diseases ,Angiology ,Randomized Controlled Trials as Topic ,Original Investigation ,Clinical Trials as Topic ,Dipeptidyl-Peptidase IV Inhibitors ,Cardiovascular safety ,business.industry ,Type 2 Diabetes Mellitus ,Dipeptides ,medicine.disease ,Clinical trial ,chemistry ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Major adverse cardiovascular events ,business ,Cardiology and Cardiovascular Medicine ,medicine.drug - 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.
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