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 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. Results 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. 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.