Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study

Aim The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (<7.4%) with minimal weight gain (<1 kg) compared with insulin glargine. Methods Patients [body mass index (BMI) > 27 kg/m2] with elevated cardiovascular risk and type 2 diabetes inadequately controlled on two or three oral antidiabetes drugs (OADs) were randomized to add-on exenatide 5-10 mu g b.i.d. (n = 118) or insulin glargine o.d. (titrated to target fasting plasma glucose <5.6 mmol/l; n = 117) for 26 weeks. Results The study population had baseline mean (s.d.) age of 56.5 (9.1) years and BMI of 34.1 (5.3) kg/m2, and 58.5% of patients were taking two OADs. Mean baseline HbA1c was 8.65 (0.68)% in the exenatide group and 8.48 (0.66)% in the insulin glargine group. The proportions of patients achieving the composite endpoint of HbA1c <7.4% with weight gain <1 kg were 53.4% for the exenatide group and 19.8% for the insulin glargine group (p <0.001 for exenatide vs. insulin glargine). Exenatide and insulin glargine did not demonstrate a significant difference in HbA1c improvements [least square (LS) mean [s.e.m.]: -1.25 [0.09]% and -1.26 [0.09]% respectively; p = 0.924], but had divergent effects on body weight (-2.73 [0.31] vs. +2.98 [0.31] kg respectively, p <0.001) after 26 weeks. There were more treatment-related adverse events with exenatide but a lower incidence of nocturnal hypoglycaemia, with no differences in overall or severe hypoglycaemia. Conclusions Additional treatment with exenatide resulted in significantly more overweight and obese patients with an elevated cardiovascular risk and type 2 diabetes achieving better glycaemic control with minimal weight gain compared with insulin glargine.