Background: Weight gain and hypoglycaemia are common adverse effects associated with anti-diabetic treatments. Aim: Our aim was to evaluate the long-term effects of adjunctive exenatide therapy on weight loss and glycaemic control in patients with type 2 diabetes. Methods: A review of medical records in a specialist diabetes clinic over 5 years identified 446 patients who were prescribed exenatide therapy. We examined change in glycosylated haemoglobin (HbA1c), weight, albumin-creatinine ratio and hypoglycaemic medication during 24 months follow up. Results: Subjects were aged 59 ? 10 years (49 women) and received exenatide in combination with oral agents and insulin (47 ). During an average of 17 ? 14 months follow up, 51 (more women than men; odds ratio 1.69, 95 confidence interval 1.14-2.49) remained on treatment. Lack of efficacy (33 ) and/or gastrointestinal (27 ) side-effects were the main reasons for treatment cessation. At 24 months, there was a reduction in HbA1c of 0.7 ? 1.2 and weight loss of 4.3 ? 5.2kg. Change in HbA1c was similar regardless of concurrent insulin therapy, yet insulin was associated with greater weight reduction (4.8 ? 5.3 vs 3.8 ? 5.1kg, P = 0.016). Independent predictors of HbA1c response were higher baseline HbA1c, longer duration of diabetes and use of insulin or sulfonylureas at study end. Predictors of weight response were baseline use of insulin or thiazolidinediones, increased age, female sex and sulfonylurea or thiazolidinediones at study end. Longer exenatide treatment duration was favourable for reducing HbA1c and weight. Conclusions: Exenatide is effective in reducing HbA1c and weight, regardless of concurrent insulin, and in a specialist diabetes outpatient clinic, is recommended for use in clinical practice.