Liraglutide effects on beta‐cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes. Issue 6 (23rd February 2017)

• Record Type: Journal Article
• Authors: Anholm, Christian; Kumarathurai, Preman; Pedersen, Lene R.; Nielsen, Olav W.; Kristiansen, Ole P.; Fenger, Mogens; Madsbad, Sten; Sajadieh, Ahmad; Haugaard, Steen B.
• Is Part Of: Diabetes, obesity & metabolism. Volume 19:Issue 6(2017)
• Page Start: 850
• Page End: 857
• Publication Date: 2017-02-23
• Subjects: beta‐cell function -- glucose effectiveness -- insulin sensitivity -- liraglutide -- type 2 diabetes; Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12891
• Languages: English
• ISSNs: 1462-8902

Abstract

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/m 2 (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.