The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

Sep 3, 2023The American journal of clinical nutrition

Weight loss from GLP-1 receptor drugs in non-diabetic people with overweight or obesity: A combined analysis of clinical trials

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Abstract

GLP-1 receptor agonists reduced body weight by an average of 5.319 kg in patients with obesity or overweight without diabetes.

In a review of 41 trials with 15,135 participants, GLP-1 receptor agonists significantly decreased body weight, body mass index, and waist circumference compared to controls.
Body weight was reduced by an average of 5.319 kg, body mass index by 2.373 kg/m², and waist circumference by 4.302 cm.
No significant reduction in total body fat was observed.
The effects of GLP-1 receptor agonists on weight loss may follow a nonlinear dose-response relationship.
Semaglutide was suggested as the most effective GLP-1 receptor agonist, with a favorable efficacy profile and moderate risk of adverse effects.

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BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity.

OBJECTIVE: To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes.

METHODS: This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models.

RESULTS: Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects. 2

CONCLUSIONS: The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.

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The Weight-loss Effect of GLP-1RAs Glucagon-Like Peptide-1 Receptor Agonists in Non-diabetic Individuals with Overweight or Obesity: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials

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