title: Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes.
abstract: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM).
  
  
  
  The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis.
  
  
  
  Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2(SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L-1× min (IQR 342; 626, P  < .0001) and DI by 1-fold, 766 (SD 824, P  < .0001). Despite a significant weight loss of -2.7 kg (-6.7; -0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect.
  
  
  
  Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.
authors.affiliation: Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark.|Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Christian
authors.identifier: 0000-0002-2669-1642
authors.initials: C
authors.lastname: Anholm
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Preman
authors.initials: P
authors.lastname: Kumarathurai
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Lene R
authors.initials: LR
authors.lastname: Pedersen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Olav W
authors.initials: OW
authors.lastname: Nielsen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Ole P
authors.initials: OP
authors.lastname: Kristiansen
authors.affiliation: Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Mogens
authors.initials: M
authors.lastname: Fenger
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sajadieh
authors.affiliation: Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark.|Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003324:Coronary Artery Disease / Q000150:complications*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007333:Insulin Resistance / Q000502:physiology; D050417:Insulin-Secreting Cells / Q000187:drug effects; D000069450:Liraglutide / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D008875:Middle Aged; D009765:Obesity / Q000150:complications
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D000069450:Liraglutide; D008687:Metformin
keywords: beta-cell function; glucose effectiveness; insulin sensitivity; liraglutide; type 2 diabetes