Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE

Original Publication: Oxford : Wiley-Blackwell, c1999-

Coronary Artery Disease/*physiopathology ; Diabetes Mellitus, Type 2/*drug therapy ; Hypoglycemic Agents/*pharmacology ; Lipolysis/*drug effects ; Liraglutide/*pharmacology ; Obesity/*physiopathology ; Oxidation-Reduction/*drug effects; Aged ; Blood Glucose/drug effects ; Coronary Artery Disease/complications ; Cross-Over Studies ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/physiopathology ; Double-Blind Method ; Drug Therapy, Combination ; Fatty Acids, Nonesterified/blood ; Female ; Humans ; Lipid Metabolism/drug effects ; Male ; Metformin/pharmacology ; Middle Aged ; Obesity/complications ; Treatment Outcome

Elevated levels of non-esterified fatty acids (NEFA) play a role in insulin resistance, impaired beta-cell function and they are a denominator of the abnormal atherogenic lipid profile that characterizes obese patients with type 2 diabetes (T2DM). We hypothesized that the GLP-1 receptor agonist liraglutide, in combination with metformin, would reduce lipolysis. In a randomized, double-blind, placebo-controlled, cross-over trial, 41 T2DM patients with coronary artery disease were randomized and treated with liraglutide-metformin vs placebo-metformin during 12- + 12-week periods with a wash-out period of at least 2 weeks before and between the intervention periods. NEFA kinetics were estimated using the Boston Minimal Model of NEFA metabolism, with plasma NEFA and glucose levels measured during a standard 180-minute frequently sampled intravenous glucose tolerance test. Liraglutide-metformin reduced estimates of lipolysis. Furthermore, placebo-metformin increased estimates of lipid oxidation, while treatment with liraglutide eliminated this effect. We conclude that liraglutide exerts a clinically relevant reduction in estimates of lipolysis and lipid oxidation which is explained, in part, by improved insulin secretion, as revealed by an intravenous glucose tolerance test.
(© 2019 John Wiley & Sons Ltd.)

Keywords: GLP-1 analogue; clinical trial; liraglutide; metformin; randomised trial; type 2 diabetes

0 (Blood Glucose)
0 (Fatty Acids, Nonesterified)
0 (Hypoglycemic Agents)
839I73S42A (Liraglutide)
9100L32L2N (Metformin)

Date Created: 20190504 Date Completed: 20200916 Latest Revision: 20200916

20240628

10.1111/dom.13761

31050161