To evaluate the 3-year efficacy and safety of exenatide once weekly (QW) for type 2 diabetes (T2D) in a large clinical population.This post hoc analysis of three DURATION studies examined pooled efficacy and adverse events with exenatide QW from the 2.5- to 3-year completer populations; insulin glargine (glargine) was a reference (DURATION-3). Patients randomized to exenatide QW during the controlled study periods continued controlled treatment (DURATION-3) or single-arm treatment (DURATION-1; DURATION-2) with exenatide QW for the study duration.In the exenatide QW group (N=329), reductions from baseline in HbA1c, fasting glucose, and body weight were maintained from weeks 4 to 156 (HbA1c: −1.1±1.3%; fasting glucose: −1.7±2.7mmol/L; body weight: −2.4±5.6kg; P<0.05). Glycemic efficacy with exenatide QW and glargine was similar (HbA1c reduction: −0.8±1.0%; N=158); body weight increased with glargine (+2.0±4.9kg). Variable reductions in systolic blood pressure and low-density lipoprotein cholesterol occurred with exenatide QW. At week 156, 48.3% and 30.7% of exenatide QW recipients achieved HbA1c goals of <7.0% and ≤6.5%, respectively. No new safety or tolerability issues were identified.Exenatide QW improved glycemic outcomes and was well tolerated in patients with T2D for up to 156weeks.