Assessing the cardio-cerebrovascular safety of vildagliptin: meta-analysis of adjudicated events from a large Phase III type 2 diabetes population

Diabetes Obes Metab. 2010 Jun;12(6):485-94. doi: 10.1111/j.1463-1326.2010.01215.x.


Aim: To assess the cardiovascular and cerebrovascular (CCV) safety of the dipeptidyl peptidase-IV inhibitor vildagliptin.

Methods: Data were pooled from 25 Phase III studies of vildagliptin, used either as monotherapy or combination therapy, with durations of 12 weeks to > or = 2 years. The safety of vildagliptin [50 mg qd (N = 1393) or 50 mg bid (N = 6116)] was assessed relative to a pool of all comparators [both placebo and active comparators (N = 6061)]. CCV events were adjudicated in a prospective, blinded fashion by an independent CCV adjudication committee. Meta-analysis of confirmed CCV events was performed with Mantel-Haenszel risk ratios (RRs); categories included in the composite endpoint were acute coronary syndrome, transient ischaemic attack (with imaging evidence of infarction), stroke and CCV death. Subgroup analyses by age (< and > or = 65 years), gender and cardiovascular (CV) risk status [high CV risk status defined as a previous history of events in the Standard MedDRA Queries of ischaemic heart disease, cardiac failure, ischaemic cerebrovascular conditions and/or embolic/thrombotic events, arterial) were also carried out. In addition, unadjusted and exposure-adjusted incidences are presented for both the composite endpoint and its components.

Results: Relative to all comparators, the RRs for the composite endpoint were < 1 for both vildagliptin 50 mg qd [RR = 0.88; 95% CI (0.37, 2.11)] and vildagliptin 50 mg bid [RR = 0.84; 95% CI (0.62, 1.14)]. The results were consistent across subgroups defined by age, gender and CV risk status, including the higher CV risk subgroups of elderly patients [RR for vildagliptin 50 mg bid vs. all comparators = 1.04; 95% CI (0.62, 1.73)], males [RR = 0.87; 95% CI (0.60, 1.24)] or patients with a high CV risk status [RR = 0.78; 95% CI (0.51, 1.19)]. The exposure-adjusted incidences of each component of the composite endpoint for vildagliptin 50 mg bid were also lower than or similar to those of all comparators.

Conclusions: In a large meta-analysis, vildagliptin was not associated with an increased risk of adjudicated CCV events relative to all comparators in the broad population of type 2 diabetes including patients at increased risk of CCV events.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / adverse effects
  • Adamantane / analogs & derivatives*
  • Cerebrovascular Disorders / chemically induced*
  • Cerebrovascular Disorders / drug therapy
  • Clinical Trials, Phase III as Topic
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / chemically induced*
  • Diabetic Angiopathies / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitriles / administration & dosage
  • Nitriles / adverse effects*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects*
  • Randomized Controlled Trials as Topic
  • Vildagliptin


  • Dipeptidyl-Peptidase IV Inhibitors
  • Nitriles
  • Pyrrolidines
  • Vildagliptin
  • Adamantane