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

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.

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_0-10 and C_max0-10 ) and second-phase secretion (AUC_10-180 and C_max10-180 ) were calculated for insulin and C-peptide. The glucose disappearance constant (K_g ) and homeostasis model assessment of β-cell function (HOMA-β) were assessed.

In 20 subjects with T2DM, dulaglutide increased mean insulin AUC_0-10 by 7.92-fold and C_max0-10 by 5.40-fold vs placebo, and mean AUC_10-180 and C_max10-180 by 2.44- and 3.78- fold, respectively. In 10 healthy subjects, dulaglutide increased the mean insulin AUC_0-10 by 3.09-fold and C_max0-10 by 2.96-fold vs placebo, and mean AUC_10-180 and C_max10-180 by 2.04- and 4.15-fold, respectively. The corresponding C-peptide values also increased. Mean K_g and HOMA-β were higher after dulaglutide compared with placebo.

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.