GLP-1 Agonists and Their Efficacy for Weight Loss: Unraveling the Best Option Through Network Meta-Analysis

Introduction: Glucagon-like peptide-1 (GLP-1) agonists have garnered significant attention as a favored pharmacological intervention for weight loss. We aimed to identify the GLP-1 agonist and dosage that generated the most significant weight loss. We conducted a network meta-analysis encompassing intra-medication comparisons, evaluating different doses of the same GLP-1 agonist, and inter-medication comparisons, examining the weight loss effects of different GLP-1 agonists. Methods: We systematically searched electronic databases for randomized controlled trials (RCTs) evaluating the efficacy of GLP-1 agonists for obesity management. We extracted percentage weight loss (mean and SD). A network meta-analysis using frequentist methods with a random-effects model was conducted. The P-score was calculated to obtain treatment ranking to identify preferred GLP-1 agonists and their dose for percentage weight change. A league table provided network estimates of each possible comparison. Comparison-adjusted funnel plot assessed publication bias. Results: A total of 14 studies comprising 18,714 participants with BMIs ≥ 30 or ≥ 27 with obesity-related comorbidities were included in the analysis. The network meta-analysis incorporated 4 GLP-1 agonists [tirzepatide, semaglutide, liraglutide, and dulaglutide] with eight treatments and placebo (Figure 1A). On network comparison with placebo, all GLP-1 agonists except for dulaglutide 0.75 mg were associated with a reduction in percentage weight with the highest effect seen with tirzepatide 15 mg (MD: -15.24%; 95% CI: -17.76% to -12.73%, Figure 1B). Tirzepatide 15 mg had the highest degree of weight loss compared to all other GLP-1 agonists at different dosages (Figure 1C). There was no difference in percentage weight change between tirzepatide 15 mg and the 10 mg dose (MD: -1.61%; 95% CI: -3.99% to 0.76%), however, 15 mg and 10 mg doses led to a 5.3% and 4% change in percentage weight loss compared to the 5 mg dose (Figure 1C). Tirzepatide 15 mg was the first-ranked treatment for weight loss at a probability of 99% (Figure 1D). Comparison-adjusted funnel plot did not show any publication bias (egger’s test p =0.772). Conclusion: Tirzepatide 15 mg emerged as a preferred intervention for weight loss among all the available GLP-1 agonists and their varying doses. Furthermore, no difference was seen between Tirzepatide 15 mg and 10 mg, suggesting the medication can be used at either dose to produce maximum effect.Figure 1.: Comparison of weight reduction among GLP-1 agonists. Figure 1A exhibits the network graph with 8 different treatments, excluding placebo. Figure 1B illustrates a forest plot with network comparison using a random effects model. It shows that all GLP-1 agonists except for dulaglutide 0.75 mg were associated with a reduction in percentage weight. Tirzepatide 15 mg had the largest effect. Figure 1C displays the percent (green) and mean difference (blue) weight reduction by GLP-1 agonist. Figure 1D contains a rankogram based on P score. Tirzepatide is shown in blue, semaglutide in red, liraglutide in green, and placebo in grey. Rankogram identifies tirzepatide 15 mg as the preferred GLP-1 agonist for percentage weight change. Dulaglutide had a P score of 0.