Glucagon-like peptide-1 receptor agonists exhibit weight loss effects in non-diabetic patients with obesity

1. This systematic review found that non-diabetic patients with obesity who received glucagon-like peptide-1 receptor agonists (GLP-1RAs) had significantly reduced body weight, body mass index, waist circumference, and waist-to-hip ratio but not total body fat, compared to control groups.

2. Overall, the relationship between GLP-1RA dose and weight loss was non-linear, but the dose-response relationship varied based on the specific GLP-1RA.

Evidence Rating Level: 1 (Excellent)

Obesity affects a large population of patients globally and has many associated morbidities. Many pharmacological and lifestyle interventions have been trialed for the treatment of obesity. Glucagon-like peptide 1-receptor agonists (GLP-1RAs) have demonstrated weight loss effects in patients with diabetes. However, the impact of these medications on weight loss in non-diabetic patients is not well understood. This study assessed the results of randomized control trials to evaluate the effect of GLP-1RAs on weight loss in non-diabetic patients.

This meta-analysis included 41 randomized controlled trials involving 15,135 participants from database inception to January 1, 2022. Studies were included if they consisted of non-diabetic participants with overweight or obesity and were randomized to treatment with any GLP-1RAs or placebo. Studies were excluded if they were not randomized controlled trials, involved patients only with diabetes, or did not report on key outcomes. The review was conducted according to PRISMA guidelines. The primary outcomes measured included body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF).

The results demonstrated that compared to controls, participants who received GLP-1RAs had significantly reduced BW, BMI, WC, and WHR, but not TBF, at the end of treatment duration. Overall, GLP-1RAs demonstrated a non-linear dose-response effect on weight loss. The dose-response relationship varied based on the different GLP-1RAs used, with semaglutide appearing to be the most effective for weight loss. However, this study was limited by the significant heterogeneity between the included trials, which may have impacted the results. Nonetheless, the results suggested that GLP-1RAs have significant weight-loss effects on non-diabetic individuals with obesity.

Click to read the study in The American Journal of Clinical Nutrition

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