BackgroundHyperinsulinemia aggravates insulin resistance and cardio-vascular disease. How the insulinotropic glucagon-like peptide-1 receptor agonist liraglutide in a physiologic post-prandial setting may act on pancreatic alpha and beta-cell function in patients with coronary artery disease (CAD) and type 2 diabetes (T2DM) is less clear.MethodsInsulin resistant patients with established CAD and newly diagnosed well-controlled T2DM were recruited to a placebo-controlled, cross-over trial with two treatment periods of 12weeks and a 2weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6mg q.d. to 1.8mg q.d. within 4weeks and metformin titrated from 500mg b.i.d to 1000mg b.i.d. within 4weeks. Before and after intervention in both 12weeks periods insulin, C-peptide, glucose, and glucagon were measured during a meal test. Beta-cell function derived from the oral glucose tolerance setting was calculated as changes in insulin secretion per unit changes in glucose concentration (B-total) and whole-body insulin resistance using ISIcomposite.ResultsLiraglutide increased the disposition index [B(total)xISI(composite), by 40% (n=24, p<0.001)] compared to placebo. Post-prandial insulin and glucose was reduced by metformin in combination with liraglutide and differed, but not significantly different from placebo, moreover, glucagon concentration was unaffected. Additionally, insulin clearance tended to increase during liraglutide therapy (n=26, p=0.06).ConclusionsThe insulinotropic drug liraglutide may without increasing the insulin concentration reduce postprandial glucose but not glucagon excursions and improve beta-cell function in newly diagnosed and well-controlled T2DM.Trial registration Clinicaltrials.gov ID: NCT01595789