title: Cardiovascular safety of sitagliptin in patients with type 2 diabetes mellitus: a pooled analysis.
abstract: OBJECTIVE
  To compare the incidence of cardiovascular events and mortality in patients with type 2 diabetes mellitus treated with sitagliptin or non-sitagliptin comparators.
  
  
  METHODS
  A 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).
  
  
  RESULTS
  In 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]).
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA. samuel_engel@merck.com
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golm
authors.forename: Deborah
authors.initials: D
authors.lastname: Shapiro
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Davies
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011719:Pyrazines / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic / Q000379:methods; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D000068900:Sitagliptin Phosphate