Liraglutide 3.0 mg for weight management: weight-loss dependent and independent effects

• Published in: Current medical research and opinion Vol. 33; no. 2; p. 225
• Main Authors: Bays, Harold, Pi-Sunyer, Xavier, Hemmingsson, Joanna Uddén, Claudius, Birgitte, Jensen, Christine B, Van Gaal, Luc
• Format: Journal Article
• Language: English
• Published: England 01.02.2017
• Subjects: Adult; Aged; Blood Glucose - drug effects; Blood Pressure; Body Weight - drug effects; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; Female; Glycated Hemoglobin A - drug effects; Humans; Hypoglycemic Agents - therapeutic use; Liraglutide - therapeutic use; Male; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Weight Loss - drug effects; liraglutide; Antiobesity medications; randomized clinical trial; GLP-1 receptor agonist; obesity therapy
• ISSN: 1473-4877
• DOI: 10.1080/03007995.2016.1251892

As an adjunct to a reduced-calorie diet and increased physical activity, treatment with liraglutide 3.0 mg for weight management provides a statistically significant and clinically meaningful weight loss of 5.7%-8.0% compared to 1.6%-2.6% with placebo. The objective of this post hoc analysis was to quantify the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key efficacy endpoints. The analysis utilized data from 4725 participants across three randomized, placebo-controlled, double-blind trials that evaluated the efficacy and safety of liraglutide 3.0 mg versus placebo, as an adjunct to a reduced-calorie diet and increased physical activity (ClinicalTrials.gov identifiers: NCT01272219, NCT01272232 and NCT01557166). The duration of two of the trials was 56 weeks; one trial was of 32 weeks' duration. A mediation analysis was performed, which ranked the relative contribution of weight loss to the treatment effects of liraglutide 3.0 mg on key cardiometabolic efficacy endpoints, Apnea-Hypopnea Index (AHI) and health-related quality of life (QoL). A limitation of this type of analysis is that it cannot conclusively prove a causal relationship. In individuals without type 2 diabetes mellitus (T2DM), endpoints predominantly driven by liraglutide-induced weight loss included waist circumference, diastolic blood pressure, triglycerides, high density lipoprotein cholesterol, AHI, and Impact of Weight on Quality of Life-Lite total and physical function scores. Endpoints predominantly independent of weight loss included the glycemic endpoints hemoglobin A1c and fasting plasma glucose in individuals with and without T2DM. Regardless of the degree of dependence on weight loss according to the mediation analysis, greater weight loss was associated with greater improvement in all endpoints. Treatment with liraglutide 3.0 mg contributes to improved cardiometabolic parameters, AHI and health-related QoL through both weight-loss dependent and weight-loss independent mechanisms.