Abstract
ObjectiveTo compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators.MethodsA post hoc assessment of cardiovascular safety in 14,611 patients was performed by pooling data from 25 double-blind studies, which randomised patients at baseline to sitagliptin 100 mg/day or a non-sitagliptin comparator (i.e., non-exposed). Included studies were limited to those at least 12 weeks in duration (range: 12 to 104 weeks). Patient-level data were used in this analysis of major adverse cardiovascular events (MACE) including ischaemic events and cardiovascular deaths. Analyses were performed in three cohorts: the entire 25-study cohort, the cohort from placebo-controlled portions of studies (n=19), and the cohort from studies comparing sitagliptin to a sulphonylurea (n=3).ResultsIn the entire cohort analysis, 78 patients had at least 1 reported MACE-related event, with 40 in the sitagliptin group and 38 in the non-exposed group. The exposure-adjusted incidence rate was 0.65 per 100 patient-years in the sitagliptin group and 0.74 in the non-exposed group (incidence rate ratio = 0.83 [95% confidence interval (CI): 0.53, 1.30]). In the analysis comparing sitagliptin to placebo, the exposure-adjusted incidence rate was 0.80 per 100-patient-years with sitagliptin and 0.76 with placebo (incidence rate ratio = 1.01 [95% CI: 0.55, 1.86]). In the analysis comparing sitagliptin to sulphonylurea, the exposure-adjusted incidence rate was 0.00 per 100 patient-years with sitagliptin and 0.86 with sulphonylurea (incidence rate ratio = 0.00 [95% CI: 0.00, 0.31]).ConclusionA pooled analysis of 25 randomised clinical trials does not indicate that treatment with sitagliptin increases cardiovascular risk in patients with type 2 diabetes mellitus. In a subanalysis, a higher rate of cardiovascular-related events was associated with sulphonylurea relative to sitagliptin.
Highlights
Type 2 diabetes mellitus is associated with an increased risk of cardiovascular disease and mortality [1,2]
10% of patients had a history of cardiovascular disease, and 81% had additional cardiovascular risk factors besides type 2 diabetes mellitus and cardiovascular disease, including hypertension (53%), history of dyslipidaemia/hypercholesterolaemia (49%), and history of smoking (39%)
The mean exposure to study drug was greater in the sitagliptin group relative to the non-exposed group: 284 dosing days relative to 264 dosing days, respectively
Summary
Type 2 diabetes mellitus is associated with an increased risk of cardiovascular disease and mortality [1,2]. In a prospective observational study, the risk of a subsequent myocardial infarction in patients with pre-existing diabetes was found to be comparable to patients with pre-existing coronary disease [9]. These and other data have supported the concept that type 2 diabetes mellitus is considered a coronary heart disease risk equivalent; treatment guidelines for lipid management for patients with type 2 diabetes parallel those for patients with prior coronary events [10]. Prevention of cardiovascular disease is a major clinical challenge in treating patients with type 2 diabetes mellitus
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