OBJECTIVES: To support a German Federal Joint Committee (G-BA) submission, a systematic review and meta-analysis feasibility were conducted to assess the efficacy and safety of the GLP-1 receptor agonist exenatide against pre-defined comparators as required by the G-BA, for the management of patients with Type 2 diabetes mellitus (T2DM). Both the short- (Byetta®) and long-acting (Bydureon®) exenatide formulations were eligible for inclusion. METHODS: Database searches (accessed September 2013) were conducted to identify eligible randomised controlled trials (RCTs) that evaluated Byetta®/Bydureon® in one of the G-BA approved indications. In the absence of appropriate head-to-head studies, the feasibility of conducting a robust meta-analysis was assessed for outcomes of interest. RESULTS: With regard to Byetta®, single head-to-head RCTs were identified for two G-BA required comparisons: Byetta®+metformin vs metformin+sulphonylurea (SU) and Byetta®+metformin+SU vs insulin+metformin. No head-to-head RCTs were identified that assessed Bydureon® vs G-BA comparators. However, two RCTs were identified which permitted an indirect comparison of Bydureon®+metformin vs metformin + SU via a common treatment (sitagliptin+metformin). Baseline patient characteristics (body weight 81–89 kg; HbA(mean difference -0.53% [95% confidence interval (CI): ‑0.84, -0.22; p=0.001]) and weight (mean difference -3.5kg [95% CI:-4.4, -2.6; p<0.001]) and a significantly lower incidence of minor hypoglycaemia (odds ratio (OR) 0.03 [95% CI: <0.00, 0.17; p<0.001]) compared with metformin+SU. The incidence of adverse events (AEs) (OR 1.06 [95% CI: 0.63, 1.79 p=0.821]) and serious AEs (OR 1.22 [95% CI: 0.26, 5.70; p=0.800]) was similar. CONCLUSIONS: Indirect comparison results indicate that in patients with T2DM, treatment with Bydureon®+metformin is associated with significant efficacy benefits and a similar safety profile compared with metformin+SU.