Effects of glucagon-like peptide-1 receptor agonists on weight loss: systematic review and meta-analyses of randomised controlled trials

Abstract

Objective To determine whether treatment with agonists of glucagon-like peptide-1 receptor (GLP-1R) result in weight loss in overweight or obese patients with or without type 2 diabetes mellitus.Design Systematic review with meta-analyses.Data sources Electronic searches (Cochrane Library, Medline, Embase, and Web of Science) and manual searches (up to May 2011).Review methods Randomised controlled trials of adult participants with a body mass index of 25 or higher; with or without type 2 diabetes mellitus; and who received exenatide twice daily, exenatide once weekly, or liraglutide once daily at clinically relevant doses for at least 20 weeks. Control interventions assessed were placebo, oral antidiabetic drugs, or insulin.Data extraction Three authors independently extracted data. We used random effects models for the primary meta-analyses. We also did subgroup, sensitivity, regression, and sequential analyses to evaluate sources of intertrial heterogeneity, bias, and the robustness of results after adjusting for multiple testing and random errors.Results 25 trials were included in the analysis. GLP-1R agonist groups achieved a greater weight loss than control groups (weighted mean difference −2.9 kg, 95% confidence interval -3.6 to -2.2; 21 trials, 6411 participants). We found evidence of intertrial heterogeneity, but no evidence of bias or small study effects in regression analyses. The results were confirmed in sequential analyses. We recorded weight loss in the GLP-1R agonist groups for patients without diabetes (-3.2 kg, -4.3 to -2.1; three trials) as well as patients with diabetes (-2.8 kg, -3.4 to -2.3; 18 trials). In the overall analysis, GLP-1R agonists had beneficial effects on systolic and diastolic blood pressure, plasma concentrations of cholesterol, and glycaemic control, but did not have a significant effect on plasma concentrations of liver enzymes. GLP-1R agonists were associated with nausea, diarrhoea, and vomiting, but not with hypoglycaemia. ConclusionsThe present review provides evidence that treatment with GLP-1R agonists leads to weight loss in overweight or obese patients with or without type 2 diabetes mellitus.

A new paradigm for treating obesity and diabetes mellitus

“…Furthermore, while DPP-4 inhibitors are weight-neutral 7 , GLP-1 receptor agonists significantly reduce body weight 8 . However, the amount of weight loss is generally moderate and could not compete with the drastic weight reduction induced by bariatric surgery.…”

Glucagon-like peptide-1 receptor agonist treatment reduces beta cell mass in normoglycaemic mice

“…GLP-1RAs decrease body weight and are associated with reduced blood pressure, improved lipid profiles and improved endothelial function in patients with type 2 diabetes [10,11]. Therefore, these compounds have also been evaluated in non-diabetic individuals with obesity or cardiovascular disease [12][13][14][15].…”

GLP-1 receptor agonists or DPP-4 inhibitors: How to guide the clinician?

“…26 Cependant, d'une façon générale et par rapport à un placebo, la perte pondérale reste relativement modérée comme le montre deux méta-analyses récentes. 27,28 Chez les patients avec une DT2, la perte pondérale moyenne pondérée est de -2.8 kg (intervalle de confiance à 95% ou IC 95% : -3,4 à -2,3) dans 18 essais cliniques contrôlés d'une durée habituelle de 6 mois à 1 an. 28 Une diminution de la pression artérielle, principalement systolique, a été rapportée de façon assez consistante dans les essais cliniques ayant testé le liraglutide ou l'exénatide, avec, par contre, une légère élévation de la fréquence cardiaque 12 .…”

“…27,28 Chez les patients avec une DT2, la perte pondérale moyenne pondérée est de -2.8 kg (intervalle de confiance à 95% ou IC 95% : -3,4 à -2,3) dans 18 essais cliniques contrôlés d'une durée habituelle de 6 mois à 1 an. 28 Une diminution de la pression artérielle, principalement systolique, a été rapportée de façon assez consistante dans les essais cliniques ayant testé le liraglutide ou l'exénatide, avec, par contre, une légère élévation de la fréquence cardiaque 12 . Quelques données rapportent également une diminution des taux de triglycérides et de l'hyperlipémie post-prandiale.…”