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.