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).
MATERIAL AND METHODS: Design: 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-weeks 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 x Si. Thirty patients of 41 randomized were available for paired analysis.
RESULTS: Baseline characteristics: 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 < 0.0001) and DI by 1-fold; 766 (SD 824, p < 0.0001). 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 cause a carry-over effect.
CONCLUSION: Liraglutide as add-on to metformin induces a clinical 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.