The association of the treatment with glucagon-like peptide-1 receptor agonist exenatide or insulin with cardiovascular outcomes in patients with type 2 diabetes: a retrospective observational study

Background: To evaluate the association of treatment with glucagon-like peptide-1 (GLP-1) receptor agonist exenatide and/or insulin on macrovascular outcomes in patients with type 2 diabetes (T2DM). Methods: We conducted a retrospective longitudinal pharmaco-epidemiological study using large ambulatory care data to evaluate the risks of heart failure (HF), myocardial infarction (MI) and stroke in established T2DM patients who received a first prescription of exenatide twice daily (EBID) or insulin between June 2005 and May 2009, with follow-up data available until December 2012. Three treatment groups were: EBID with oral antidiabetes drugs (OADs) (EBID, n = 2804), insulin with OADs (Insulin, n = 28551), and those who changed medications between EBID and insulin or had combination of EBID and insulin during follow-up, along with OADs (EBID + insulin, n = 7870). Multivariate Cox-regression models were used to evaluate the association of treatment groups with the risks of macrovascular events. Results: During a median 3.5 years of follow-up, cardiovascular event rates per 1000 person-years were significantly lower for the EBID and EBID + insulin groups compared to the insulin group (HF: 4.4 and 6.1 vs. 17.9; MI: 1.1 and 1.2 vs. 2.5; stroke: 2.4 and 1.8 vs. 6.1). Patients in the EBID/EBID + insulin group had significantly reduced risk of HF, MI and stroke by 61/56%, 50/38% and 52/63% respectively, compared to patients in the insulin group (p < 0.01). Conclusions: Treatment with exenatide, with or without concomitant insulin was associated with reduced macrovascular risks compared to insulin; although inherent potential bias in epidemiological studies should be considered.