Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis

Cardiovascular Diabetology

Original Investigation

Michael J Davies¹  Gregory T Golm¹  Samuel S Engel¹  Deborah Shapiro¹  Keith D Kaufman¹  Barry J Goldstein¹ 

[1] Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA;

关键词: Metformin;    Rosiglitazone;    Pioglitazone;    Sitagliptin;    Glimepiride;   

DOI  :  10.1186/1475-2840-12-3

 received in 2012-09-18, accepted in 2012-12-06,  发布年份 2013

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Engel et al.; licensee BioMed Central Ltd. 2013