Once-weekly dulaglutide 1.5 mg restores insulin secretion in response to intravenous glucose infusion.

AIMS: To evaluate the effects of dulaglutide 1.5 mg on first- and second-phase insulin secretion in response to an intravenous (i.v.) glucose bolus challenge, in subjects with type 2 diabetes mellitus (T2DM; primary objective) and in healthy subjects. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, 2-period crossover study, subjects received a single subcutaneous injection of dulaglutide 1.5 mg or placebo on day 1 of each period. On day 3, subjects underwent a 6-hour insulin infusion, followed by an i.v. glucose bolus and a glucagon challenge during hyperglycaemia. Areas under the concentration-time curve and maximum concentrations for first- (AUC and C ) and second-phase secretion (AUC and C ) were calculated for insulin and C-peptide. The glucose disappearance constant (K ) and homeostasis model assessment of β-cell function (HOMA-β) were assessed. RESULTS: In 20 subjects with T2DM, dulaglutide increased mean insulin AUC by 7.92-fold and C by 5.40-fold vs placebo, and mean AUC and C by 2.44- and 3.78- fold, respectively. In 10 healthy subjects, dulaglutide increased the mean insulin AUC by 3.09-fold and C by 2.96-fold vs placebo, and mean AUC and C by 2.04- and 4.15-fold, respectively. The corresponding C-peptide values also increased. Mean K and HOMA-β were higher after dulaglutide compared with placebo. CONCLUSIONS: In subjects with T2DM, a single dulaglutide 1.5-mg dose restored the first-phase insulin secretion in response to an i.v. glucose bolus, increased the second-phase insulin response and enhanced β-cell function.