Monotherapy with the once‐weekly GLP‐1 analogue dulaglutide for 12 weeks in patients with Type 2 diabetes: dose‐dependent effects on glycaemic control in a randomized, double‐blind, placebo‐controlled study

Diabet. Med. 29, 1260–1267 (2012) Abstract Aims Evaluate dose‐dependent effects of once‐weekly dulaglutide, a glucagon‐like peptide‐1 analogue, on glycaemic control in patients with Type 2 diabetes treated with lifestyle measures with or without previous metformin. Methods This 12‐week, double‐blind, placebo‐controlled, dose–response trial randomized 167 patients who were anti‐hyperglycaemic medication‐naïve or had discontinued metformin monotherapy [mean baseline HbA 1c 59 ± 8 to 61 ± 8 mmol/mol (7.6 ± 0.7 to 7.8 ± 0.8%)] to once‐weekly injections of placebo or dulaglutide (0.1, 0.5, 1.0 or 1.5 mg). Results A significant dose‐dependent reduction in HbA 1c (least squares mean ± se ) was observed across doses ( P < 0.001). HbA 1c reductions in the 0.5, 1.0 and 1.5 mg dulaglutide groups were greater than in the placebo group [−10 ± 1, −11 ± 1 and −11 ± 1 vs. 0 ± 1 mmol/mol (−0.9 ± 0.1, −1.0 ± 0.1 and −1.0 ± 0.1 vs. 0.0 ± 0.1%), respectively, all P < 0.001]. Dose‐dependent reductions in fasting plasma glucose were also observed [least squares mean difference (95% CI) ranging from −0.43 (−1.06 to 0.19) mmol/l for dulaglutide 0.1 mg to −1.87 (−2.56 to −1.19) mmol/l for dulaglutide 1.5 mg, P < 0.001]. Dose‐dependent weight loss was demonstrated across doses ( P = 0.009), but none of the groups were different from placebo. The most common adverse events were nausea and diarrhoea. Conclusions The observed dulaglutide dose‐dependent reduction in HbA 1c and its acceptable safety profile support further clinical development for treatment of Type 2 diabetes.