Christian Anholm1,2, Preman Kumarathurai2, Lene R Pedersen2, Olav W Nielsen2, Ole P Kristiansen2, Mogens Fenger3, Sten Madsbad4, Ahmad Sajadieh2, Steen B Haugaard1,5. 1. Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark. 2. Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark. 3. Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre, Denmark. 4. Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark. 5. Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
Abstract
AIMS: 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). METHODS: 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. RESULTS: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fastingplasma-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. CONCLUSION: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.
RCT Entities:
AIMS: 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/obesepatients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). METHODS: 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. RESULTS: 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. CONCLUSION: 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: Mara Suleiman; Lorella Marselli; Miriam Cnop; Decio L Eizirik; Carmela De Luca; Francesca R Femia; Marta Tesi; Silvia Del Guerra; Piero Marchetti Journal: Int J Mol Sci Date: 2022-07-04 Impact factor: 6.208
Authors: Adrian Villalba; Silvia Rodriguez-Fernandez; David Perna-Barrull; Rosa-Maria Ampudia; Laia Gomez-Muñoz; Irma Pujol-Autonell; Eva Aguilera; Mireia Coma; Mary Cano-Sarabia; Federico Vázquez; Joan Verdaguer; Marta Vives-Pi Journal: Front Endocrinol (Lausanne) Date: 2020-05-13 Impact factor: 5.555