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

Yupeng Liu; Binye Ruan; Huinan Jiang; Siyu Le; Yi Liu; Xuemei Ao; Yufeng Huang; Xudong Shi; Ru Xue; Xiaoyi Fu; Shuran Wang

doi:10.1016/j.ajcnut.2023.04.017

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

Am J Clin Nutr. 2023 Sep;118(3):614-626. doi: 10.1016/j.ajcnut.2023.04.017. Epub 2023 Aug 8.

Authors

Yupeng Liu¹, Binye Ruan², Huinan Jiang², Siyu Le², Yi Liu², Xuemei Ao², Yufeng Huang², Xudong Shi², Ru Xue², Xiaoyi Fu³, Shuran Wang⁴

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
² Department of Nutrition and Food Hygiene, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China.
³ Department of Nutrition and Food Hygiene, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China. Electronic address: fuxiaoyi@wmu.edu.cn.
⁴ Department of Nutrition and Food Hygiene, School of Public Health and Management, Wenzhou Medical University, Wenzhou, China. Electronic address: shuranwang@wmu.edu.cn.

PMID: 37661106
DOI: 10.1016/j.ajcnut.2023.04.017

Abstract

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/m², 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.

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.

Keywords: dose-response meta-analysis; glucagon-like peptide-1 receptor agonists (GLP-1RAs); randomized controlled trials (RCTs); trial sequential analysis (TSA); weight loss.

Publication types

Meta-Analysis
Systematic Review
Research Support, Non-U.S. Gov't

MeSH terms

Body Weight
Glucagon-Like Peptide-1 Receptor*
Humans
Obesity / drug therapy
Overweight* / drug therapy
Randomized Controlled Trials as Topic
Weight Loss

Substances

Glucagon-Like Peptide-1 Receptor