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Review
. 2012 Jan 10:344:d7771.
doi: 10.1136/bmj.d7771.

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

Tina Vilsbøll  1 , Mikkel Christensen, Anders E Junker, Filip K Knop, Lise Lotte Gluud
Affiliations
Review

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

Tina Vilsbøll et al. BMJ. .

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.

Conclusions: The 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.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare: no received support from any organisation for the submitted work; no relationships with any organisations that might have an interest in the submitted work in the previous 3 years; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow chart for identification and selection of included randomised trials
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Fig 2 Meta-analysis of change in body weight (kg) in included trials after at least 20 weeks of treatment, using random effects model
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Fig 3 Meta-analysis of change in systolic blood pressure (mm Hg) in included trials after at least 20 weeks of treatment, using random effects model
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Fig 4 Meta-analysis of change in diastolic blood pressure (mm Hg) in included trials after at least 20 weeks of treatment, using random effects model
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Fig 5 Meta-analysis of change in concentration of total cholesterol (mmol/L) in included trials after at least 20 weeks of treatment, using random effects model
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Fig 6 Meta-analysis of change in concentration of alanine aminotransferase (U/L) in included trials after at least 20 weeks of treatment, using fixed effects model
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Fig 7 Meta-analysis of reduction in HbA1c percentage in included trials after at least 20 weeks of treatment, using random effects model
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