title: Once-weekly dulaglutide 1.5 mg restores insulin secretion in response to intravenous glucose infusion.
abstract: 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- (AUC0-10and Cmax0-10) and second-phase secretion (AUC10-180and Cmax10-180) were calculated for insulin and C-peptide. The glucose disappearance constant (Kg) and homeostasis model assessment of β-cell function (HOMA-β) were assessed.
  
  
  
  In 20 subjects with T2DM, dulaglutide increased mean insulin AUC0-10by 7.92-fold and Cmax0-10by 5.40-fold vs placebo, and mean AUC10-180and Cmax10-180by 2.44- and 3.78- fold, respectively. In 10 healthy subjects, dulaglutide increased the mean insulin AUC0-10by 3.09-fold and Cmax0-10by 2.96-fold vs placebo, and mean AUC10-180and Cmax10-180by 2.04- and 4.15-fold, respectively. The corresponding C-peptide values also increased. Mean Kgand 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.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Amparo
authors.initials: A
authors.lastname: de la Peña
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Corina
authors.initials: C
authors.lastname: Loghin
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Xuewei
authors.initials: X
authors.lastname: Cui
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
authors.affiliation: Lilly-NUS Centre for Clinical Pharmacology, Singapore.
authors.forename: Ronan P
authors.initials: RP
authors.lastname: Kelly
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005934:Glucagon; D004763:Glucagon-Like Peptides / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage*; D007262:Infusions, Intravenous; D007279:Injections, Subcutaneous; D007328:Insulin / Q000097:blood*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D007004:Hypoglycemic Agents; D007141:Immunoglobulin Fc Fragments; D007328:Insulin; D011993:Recombinant Fusion Proteins; D004763:Glucagon-Like Peptides; D005934:Glucagon; D005947:Glucose; C555680:dulaglutide
keywords: dulaglutide; insulin secretion; type 2 diabetes; β-cells