Liraglutide effects on beta‐cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes

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 ( S i) and glucose effectiveness ( S g) 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 ), S i and S g were estimated by the B ergman M inimal M odel, enabling calculation of beta‐cell function; D isposition Index ( DI ) =  AIRg  ×  S i. 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 , S i or S g. 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 S i and S g are neutral.