Association of glucagon-like peptide 1 analogs and agonists administered for obesity with weight loss and adverse events: a systematic review and network meta-analysis

Abstract

Background: Comparative effectiveness of 7 glucagon-like peptide 1 (GLP-1) agents on weight loss (WL) in obesity remains unknown. Methods: We performed a systematic review, network meta-analysis (NMA) utilizing the following data sources: MEDLINE, EMBASE, Scopus, Cochrane Central and clinical trial registries, from inception to March 2, 2021. The prespecified criteria for study inclusion were randomized clinical trials (RCTs) of 12 weeks' duration. The data appraisal and extraction were performed by two investigators independently, using the published reports. The main outcomes and statistical methods were weight loss over placebo (WLOP) and adverse events (AEs) among GLP-1 agents using random-effects NMA (frequentist approach); relative ranking using surface under the cumulative ranking (SUCRA) method and certainty of evidence using grading of recommendations, assessment, development and evaluations (GRADE). Findings: 64 RCTs (from 2004 to 2021) included 27018 patients (median of age, 55.1 years old; 57.4% women; baseline weight 94.8kg and BMI 33.0kg/m 2 ; trial duration 26 weeks). Direct meta-analysis showed significant WLOP with: -1.44kg (95% CI, -2.14 to -0.74) with dulaglutide 1.5 mg; -1.82kg (-2.42 to -1.23) with exenatide immediate release (IR); -2.20kg (-4.31 to -0.08) with exenatide extended release (ER); -3.20kg (-6.53 to 0.15) with efpeglenatide; -2.72kg (-3.35 to -2.09) with liraglutide 1.8mg; -4.49kg (-5.26 to -3.72) with liraglutide >1.8mg; -0.62kg (-1.22 to -0.02) with lixisenatide; -4.33kg (-5.71 to -3.00) with semaglutide SQ <2.4mg; -9.88kg (-13.17 to -6.59) with semaglutide SQ 2.4mg; -2.73kg (-4.81 to -0.65) with semaglutide oral; and -1.71kg (-2.64 to -0.78) with taspoglutide. Highest WLOP were with semaglutide SQ 2.4mg and <2.4mg, and liraglutide >1.8mg (SUCRAs 100, 86.1, 82.8 respectively). Highest SUCRAs for discontinuation due to AEs were with taspoglutide and liraglutide >1.8mg. Risk of bias was high or unclear for random sequence generation (29.7%), allocation concealment (26.6%), and incomplete outcome data (26.6%). Heterogeneity (I 2 >50%) in WL and AEs reflected magnitude, not direction of effect.

The Link Between Obesity and the Skin

“…Beyond injection site reactions, semaglutide has been suspected to cause hair loss. However, this was not confirmed by other studies ( 67 , 68 ). We refer the reader to a former work of our group revealing the adverse skin reactions to metformin, commonly used off-label for the treatment of obesity ( 69 ).…”

“…Novel players, such as liraglutide, was shown to induce injection site reactions such as erythema, pruritus, and rash. A single report also disclosed vesiculopustular dermatosis caused by this agent (66,67). Beyond injection site reactions, semaglutide has been suspected to cause hair loss.…”

A 2022 update on the epidemiology of obesity and a call to action: as its twin COVID-19 pandemic appears to be receding, the obesity and dysmetabolism pandemic continues to rage on

“…Concerning pharmacotherapy for the more conventional cases of obesity, glucagon-like peptide-1 (GLP-1) analogs or receptor agonists play a role in regulating eating behavior by slowing gastric emptying, inducing postprandial satiety, and reducing appetite and food consumption by acting on the hypothalamus, limbic reward system and cortex. Liraglutide and semaglutide have been suggested to be the most efficacious GLP-1 receptor agonists to induce weight loss over at least 12 weeks of treatment (−4.49 kg and − 9.88 kg, respectively) [54] . Importantly, it has been demonstrated that the weight reducing effect of these agents is associated with changes in regional fat stores while lean body mass is preserved resulting in a favorable effect on metabolic and cardiovascular risks of obesity [55] .…”

Efficacy and safety of semaglutide on weight loss in obese or overweight patients without diabetes: A systematic review and meta-analysis of randomized controlled trials

“…Meta-analyses evaluating the efficacy and safety between semaglutide and placebo in obese patients have been conducted previously. Vosoughi et al (2021) and He et al (2022) both explored the weight loss effect of once-weekly semaglutide for obesity, involving patients with or without diabetes. Iqbal et al (2022) and Zhong et al (2022) designed the study in non-diabetic patients intriguingly, but only contained three or four RCTs about semaglutide and placebo.…”