The Antiobesity Effect and Safety of GLP-1 Receptor Agonist in Overweight/Obese Patients Without Diabetes: A Systematic Review and Meta-Analysis

Abstract

To determine the antiobesity effect and safety of glucagon-like peptide-1 receptor agonist (GLP-1RA) including liraglutide, exenatide and semaglutide treatment in overweight /obese patients without diabetes. All randomized controlled trials (RCTs) which reported antiobesity effect and safety of GLP-1RA in overweight/obese patients without diabetes in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. The random-effect model was used to pool data extracted from included literatures. The weighted mean difference (WMD), odds ratio (OR) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD 42020173199). The sources of intertrial heterogeneity, bias and the robustness of results were evaluated by subgroup analysis, sensitivity analysis and regression analysis, respectively. A total of 24 RCTs were recruited in the present analysis which included 5867 patients. The results showed that the treatment of overweight/obese patients without diabetes with GLP-1RAs including liraglutide, exenatide and semaglutide significantly achieved greater weight loss than placebo [WMD=-5.39,95%CI (-6.82, -3.96)] and metformin [WMD=-5.46,95%CI (-5.87, -5.05)]. The subgroup analysis showed that semaglutide displayed the most obvious antiobesity effect in terms of weight loss, the reduction of body mass index (BMI) and waist circumference (WC). However, GLP-1RAs treatments had more gastrointestinal adverse events (such as nausea and vomiting) than placebo and Met. The subgroup analysis also represented that semaglutide displayed the lowest risk of gastrointestinal adverse events among three kinds of GLP-1RAs. Our meta-analysis demonstrated that GLP-1RA had a superior antiobesity effect than placebo/Met in overweight/obese patients without diabetes in terms of body weight, BMI, and WC, especially for semaglutide, which had more obvious antiobesity effect and lower GI adverse events than liraglutide and exenatide.

The Possible Effect of the Long-Term Use of Glucagon-like Peptide-1 Receptor Agonists (GLP-1RA) on Hba1c and Lipid Profile in Type 2 Diabetes Mellitus: A Retrospective Study in KAUH, Jeddah, Saudi Arabia

“…Hence, GLP-1RAs act centrally on the brain–adipcyte axis. This mechanism could explain the anti-obesity effect of GLP-1RAs [ 25 , 36 ].…”

Effect of Glucagon-like Peptide-1 Receptor Agonists on Cardio-Metabolic Risk Factors among Obese/Overweight Individuals Treated with Antipsychotic Drug Classes: An Updated Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…Evidence of anti-obesity effects of GLP-1RAs is solid and robust, especially with liraglutide and semaglutide [ 12 , 13 ]. Liraglutide 3.0 mg once daily and semaglutide 2.4 mg once weekly have been approved by the FDA for the treatment of obesity, even in the absence of T2DM as a co-morbidity, since 2014 and 2021, respectively.…”

“…However, based on their safety and efficacy profiles and their cardiovascular and renal efficacy [ 36 , 37 ], as well, it seems that GLP-1RAs, and especially liraglutide, semaglutide, and dulaglutide, should be preferred for weight management in this patient population. Regarding their safety, GLP-1RAs have been linked to mild, mostly transient gastrointestinal adverse events (nausea, vomiting, and diarrhea), while no major safety issues have arisen with their use [ 12 , 13 ]. Based on the well-demarcated side effects of GLP-1RAs, the present meta-analysis did not address safety outcomes in this specific population.…”

“…Glucagon-like peptide-1 receptor agonists (GLP-1RAs) constitute a drug class primarily designed for the treatment of patients with T2DM, representing today’s cornerstone treatment approach for this disease. However, according to their safety and efficacy profiles, GLP-1RAs have also been utilized for the treatment of obesity, even in the absence of underlying T2DM [ 11 , 12 , 13 ]. Iqbal and colleagues recently demonstrated that GLP-1RAs compared to controls resulted in a significant decrease in body weight of 7.1 kg in a total of 11,459 enrolled subjects [ 12 ].…”

“…Iqbal and colleagues recently demonstrated that GLP-1RAs compared to controls resulted in a significant decrease in body weight of 7.1 kg in a total of 11,459 enrolled subjects [ 12 ]. In another meta-analysis by Guo et al, in a total of 5867 enrolled obese subjects without concomitant T2DM, it was shown that GLP-1RAs compared to controls led to a significant weight loss of 5.39 kg [ 13 ].…”