Abstract
Abstract
Background
Hyperinsulinemia 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.
Methods
Insulin 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 12 weeks and a 2 weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6 mg q.d. to 1.8 mg q.d. within 4 weeks and metformin titrated from 500 mg b.i.d to 1000 mg b.i.d. within 4 weeks. Before and after intervention in both 12 weeks 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 (Btotal) and whole-body insulin resistance using ISIcomposite.
Results
Liraglutide increased the disposition index [Btotal × ISIcomposite, 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).
Conclusions
The 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
Funder
Novo Nordisk
Hjerteforeningen
A.P. Møller og Hustru Chastine Mc-Kinney Møllers Fond til almene Formaal
Dept. of internal medicine, University Hospital of Copenhagen Amager
The Clinical Research Center, University Hospital of Copenhagen Hvidovre
The Bispebjerg Hospital Research Foundation
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology, Diabetes and Metabolism,Internal Medicine
Cited by
12 articles.
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