Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes

Cardiovasc Diabetol. 2011 Mar 16;10:22. doi: 10.1186/1475-2840-10-22.

Abstract

It is important for patients that treatments for diabetes not increase cardiovascular (CV) risk. The objective of this analysis was to examine retrospectively the CV safety of exenatide BID, a GLP-1 receptor agonist approved for treating hyperglycemia in patients with type 2 diabetes not adequately controlled with diet and exercise. Individual participant data was pooled to assess the relative risk (RR) of CV events with exenatide BID versus a pooled comparator (PC) group treated with either placebo or insulin from 12 controlled, randomized, clinical trials ranging from 12-52 weeks. Mean baseline values for HbA1c (8.33-8.38%), BMI (31.3-31.5 kg/m2), and duration of diabetes (8 y) were similar between groups. Trials included patients with histories of microvascular and/or macrovascular disease. Customized primary major adverse CV events (MACE) included stroke, myocardial infarction, cardiac mortality, acute coronary syndrome, and revascularization procedures. The Primary MACE RR (0.7; 95% CI 0.38, 1.31), calculated by the Mantel-Haenszel method (stratified by study), suggested that exenatide use (vs. PC) did not increase CV risk; this result was consistent across multiple analytic methods. Because the trials were not designed to assess CV outcomes, events were identified retrospectively from a list of preferred terms by physicians blinded to treatment. Other limitations included the low number of CV events, the short duration of trials (≤1 y), and a single active comparator (insulin). The results of these analyses are consistent with those of a recent retrospective analysis of a large insurance database that found that patients treated with exenatide twice daily were less likely to have a CV event than were patients treated with other glucose-lowering therapies.

Keywords: GLP-1 receptor agonist, diabetes, cardiovascular safety.

Publication types

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

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / chemically induced*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Evidence-Based Medicine
  • Exenatide
  • Female
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / adverse effects*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Peptides / administration & dosage
  • Peptides / adverse effects*
  • Proportional Hazards Models
  • Randomized Controlled Trials as Topic
  • Receptors, Glucagon / agonists*
  • Receptors, Glucagon / metabolism
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Venoms / administration & dosage
  • Venoms / adverse effects*

Substances

  • Biomarkers
  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Peptides
  • Receptors, Glucagon
  • Venoms
  • hemoglobin A1c protein, human
  • Exenatide