title: Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus.
abstract: OBJECTIVE
  To assess the effect of liraglutide, a once-daily human glucagon-like peptide-1 analogue on pancreatic B-cell function. methods: Patients with Type 2 diabetes (n = 39) were randomized to treatment with 0.65, 1.25 or 1.9 mg/day liraglutide or placebo for 14 weeks. First- and second-phase insulin release were measured by means of the insulin-modified frequently sampled intravenous glucose tolerance test. Arginine-stimulated insulin secretion was measured during a hyperglycaemic clamp (20 mmol/l). Glucose effectiveness and insulin sensitivity were estimated by means of the insulin-modified frequently sampled intravenous glucose tolerance test.
  
  
  RESULTS
  The two highest doses of liraglutide (1.25 and 1.9 mg/day) significantly increased first-phase insulin secretion by 118 and 103%, respectively (P < 0.05). Second-phase insulin secretion was significantly increased only in the 1.25 mg/day group vs. placebo. Arginine-stimulated insulin secretion increased significantly at the two highest dose levels vs. placebo by 114 and 94%, respectively (P < 0.05). There was no significant treatment effect on glucose effectiveness or insulin sensitivity.
  
  
  CONCLUSIONS
  Fourteen weeks of treatment with liraglutide showed improvements in first- and second-phase insulin secretion, together with improvements in arginine-stimulated insulin secretion during hyperglycaemia.
authors.affiliation: Department of Internal Medicine F, Gentofte Hospital, Gentofte, Denmark. t.vilsboll@dadlnet.dk
authors.forename: T
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: B
authors.initials: B
authors.lastname: Brock
authors.forename: H
authors.initials: H
authors.lastname: Perrild
authors.forename: K
authors.initials: K
authors.lastname: Levin
authors.forename: H-H
authors.initials: HH
authors.lastname: Lervang
authors.forename: K
authors.initials: K
authors.lastname: Kølendorf
authors.forename: T
authors.initials: T
authors.lastname: Krarup
authors.forename: O
authors.initials: O
authors.lastname: Schmitz
authors.forename: M
authors.initials: M
authors.lastname: Zdravkovic
authors.forename: T
authors.initials: T
authors.lastname: Le-Thi
authors.forename: S
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D002096:C-Peptide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D054795:Incretins / Q000378:metabolism; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000378:metabolism*; D000069450:Liraglutide; D008297:Male; D008875:Middle Aged; D018027:Receptors, Glucagon / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D054795:Incretins; D018027:Receptors, Glucagon; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1