title: Cardiovascular safety of exenatide BID: an integrated analysis from controlled clinical trials in participants with type 2 diabetes.
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.
  
  
  BACKGROUND
  GLP-1 receptor agonist, diabetes, cardiovascular safety.
authors.affiliation: MedStar Health Research Institute, Hyattsville, MD, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Ratner
authors.forename: Jenny
authors.initials: J
authors.lastname: Han
authors.forename: Dawn
authors.initials: D
authors.lastname: Nicewarner
authors.forename: Irina
authors.initials: I
authors.lastname: Yushmanova
authors.forename: Byron J
authors.initials: BJ
authors.lastname: Hoogwerf
authors.forename: Larry
authors.initials: L
authors.lastname: Shen
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D019317:Evidence-Based Medicine; D000077270:Exenatide; D005260:Female; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000009:adverse effects*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D014688:Venoms / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; C000593833:GLP1R protein, human; C517652:hemoglobin A1c protein, human