OBJECTIVES: The incretin mimetic exenatide improves glycaemic control with associated weight reduction in patients with type 2 diabetes (T2DM) treated with metformin (MET) and/or a sulphonylurea (SU), or MET and/or a thiazolidinedione. As a drug's pharmacokinetics and pharmacodynamics can vary with age, we explored exenatide's efficacy and safety for patients <65 y and =65 y in this post-hoc analysis. METHODS: Patients completing =3 y of exenatide treatment on background therapies of MET and/or an SU (N=217, age 58±10 y, 64% male, weight 99±18 kg, HbA1c 8.2±1.0%, fasting plasma glucose [FPG] 9.6±2.5 mmol/L, diabetes duration 8±6 y; mean±SD) had statistically significant (P<0.05) mean (±SE) changes in HbA1c (-1.0±0.1%), FPG (-1.3±0.2 mmol/L), and weight (-5.3±0.4 kg). The two subgroups (baseline age <65 y, N=161, 53±7 y, and =65 y, N=56, 70±4 y) differed in baseline duration of diabetes (7±6 y, 11±6 y). RESULTS: The mean (±SE) changes in HbA1c (-0.9±0.1%, -1.2±0.2%), weight (-5.2±0.5 kg, -5.4±0.6 kg), and FPG (-1.1±0.3 mmol/L, -1.8±0.3 mmol/L) were not statistically different for the two subgroups (all, P>0.1). In patients completing 3.5 y of exenatide, changes in lipids for the <65 y subgroup (N=118) and =65 y subgroup (N=33) were not statistically different, as follows (mmol/L): HDL cholesterol (+0.21±0.02, +0.25±0.03), LDL cholesterol (-0.28±0.09, -0.37±0.15), total cholesterol (-0.26±0.09, -0.33±0.16), and triglycerides (-0.49±0.17, -0.52±0.14) (all, P>0.2). Nausea and hypoglycaemia, the most common adverse events, occurred at similar rates in both subgroups. The only case of severe hypoglycaemia occurred in a patient <65 y whose background therapies were MET and an SU. CONCLUSION: In summary, in this open-label extension study of T2DM patients treated with MET and/or an SU, exenatide exposure =3 y resulted in similar safety profiles and improvements in glycaemic control and lipid concentrations, with associated weight reductions for patients =65 y and <65 y.