Risk of Cardiovascular Disease Events in Patients With Type 2 Diabetes Prescribed the Glucagon-Like Peptide 1 (GLP-1) Receptor Agonist Exenatide Twice Daily or Other Glucose-Lowering Therapies

Abstract

OBJECTIVETo test the hypothesis that exenatide twice daily reduces the relative incidence of cardiovascular disease (CVD) events among patients with type 2 diabetes compared with other glucose-lowering agent(s).RESEARCH DESIGN AND METHODSA retrospective database analysis was performed of the LifeLink database of medical and pharmaceutical insurance claims for June 2005 through March 2009. Patients with no history in the preceding 9 months of myocardial infarction, ischemic stroke, or coronary revascularization procedure were assigned to the exenatide-initiated or non–exenatide-initiated cohorts based on the first new prescription filled and reassigned if exenatide was prescribed or discontinued. Incident CVD events (myocardial infarction, ischemic stroke, or coronary revascularization procedure) were identified by ICD-9-CM diagnosis codes. Patient outcomes were adjusted for differences in clinical and demographic characteristics and compared using propensity score–weighted discrete time survival analysis with time-varying exposure to exenatide.RESULTSA total of 39,275 patients with type 2 diabetes were treated with exenatide twice daily, and 381,218 patients were treated with other glucose-lowering therapies. Patients who initiated exenatide were more likely to have prior ischemic heart disease, obesity, hyperlipidemia, hypertension, and/or other comorbidities at baseline. Exenatide-treated patients were less likely to have a CVD event than non–exenatide-treated patients (hazard ratio 0.81; 95% CI 0.68–0.95; P = 0.01) and lower rates of CVD-related hospitalization (0.88; 0.79–0.98; P = 0.02) and all-cause hospitalization (0.94; 0.91–0.97; P < 0.001).CONCLUSIONSExenatide twice-daily treatment was associated with a lower risk of CVD events and hospitalizations than treatment with other glucose-lowering therapies.

Adverse Effects of GLP-1 Receptor Agonists

“…The available data do not indicate any increase in cardiovascular events with GLP-1 receptor agonists [89][90][91]. A meta-analysis of 36 trials with a duration ≥12 weeks showed that the MantelHaenszel OR (MH-OR) for major cardiovascular events versus placebo or other comparators was 0.74 for all GLP-1 receptor agonists (95% CI: 0.50-1.08, p = 0.12), 0.85 for exenatide (95% CI: 0.50-1.45, p = 0.55) and 0.69 for liraglutide (95% CI: 0.40-1.22, p = 0.20) [92].…”

Glucagon-Like Receptor 1 Agonists and DPP-4 Inhibitors: Potential Therapies for the Treatment of Stroke

“…15 A number of clinical trials with GLP-1R agonists are ongoing where the effect on stroke is one of the outcome measures (see Table 1B). While most of these studies are performed in diabetic patients focusing on combined cardiovascular outcome measures, a few of them are directly focusing on stroke patients.…”

Observational studies of the association between glucose-lowering medications and cardiovascular outcomes: addressing methodological limitations

“…A few studies accounted for time-varying exposures by using Cox models analysing exposure to drugs as a timedependent variable [19,64,71,72,77,78]. These models make the assumption that treatment changes are independent of cardiovascular outcomes and may lead to biased results in the presence of patient characteristics that vary over time, affecting both diabetes treatment choice and cardiovascular risk [79], a likely scenario in the context of a chronic disease requiring therapy adjustments commensurate to its natural progression.…”