AIMS: Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors. METHODS: This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean +/- SD) HbA1c, 8.1 +/- 1.2%; fasting blood glucose (FBG), 166 +/- 48 mg/dl; weight, 94.3 +/- 19.4 kg; systolic/diastolic blood pressure (SBP/DBP), 129 +/- 15/78 +/- 9 mm Hg; total cholesterol, 178.5 +/- 41.9 mg/dl; low-density lipoprotein (LDL), 100.1 +/- 35.0 mg/dl; high-density lipoprotein (HDL), 44.5 +/- 11.6 mg/dl; triglycerides, 155.6 +/- 3.3 mg/dl; alanine aminotransferase (ALT), 32.1 +/- 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials. RESULTS: At 52 weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, -1.3 (0.05)%], FBG [-36.3 (2.02) mg/dl], body weight [-2.6 (0.19) kg], SBP/DBP [-3.6 (0.56) mm Hg/-1.2 (0.34) mm Hg], total cholesterol, -4.4 (1.33) mg/dl; LDL, -2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, -7 (1.6)%], and ALT [-4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea. CONCLUSIONS: With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome (HbA1c < 7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals (HbA1c < 7%, BP < 130/80 mm Hg, LDL < 100 mg/dl).