Semaglutide 2.4 Mg for the Management of Overweight and Obesity: Systematic Literature Review and Meta-Analysis

Abstract

Purpose Semaglutide has demonstrated safe and effective weight loss for overweight and obesity, including participants with concomitant type 2 diabetes mellitus (T2DM), in randomized placebo-controlled trials (RCTs). We conducted a systematic literature review (SLR) and network meta-analyses (NMA) to compare weekly semaglutide 2.4 mg with pharmacological comparators for weight management in overweight or obesity. Methods The SLR was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) checklist. NMAs were performed to compare weight change for semaglutide 2.4 mg with comparators using data identified in the SLR. The populations of interest were total population, normal glucose tolerance, non-T2DM, pre-diabetes, and T2DM. Included outcomes were weight change from baseline (CFB, %) at 52 weeks and proportion of participants losing ≥5% baseline fasting body weight at 12 weeks (at full therapeutic dose). Results The SLR identified 108 RCTs examining non-surgical interventions, of which 41 were considered for inclusion in the NMAs. In all populations, semaglutide 2.4 mg was associated with a greater percentage weight CFB with 52 weeks of treatment versus all available comparators. In all populations, semaglutide was associated with a higher likelihood of participants losing ≥5% of baseline fasting body weight at 12 weeks versus all available comparators. Conclusion In NMA, semaglutide 2.4 mg demonstrated effective weight loss (≥5%) in the total population and all subpopulations of glucose tolerance versus active comparators. Semaglutide is an effective treatment that may address unmet need in the management of overweight and obesity.

A model‐based approach to predict individual weight loss with semaglutide in people with overweight or obesity

“…Using a prediction tool could help HCPs manage weight‐loss expectations in people with overweight or obesity when initiating semaglutide treatment, determine appropriate timing of follow‐up visits and adjust therapy when necessary (based on decreased bias and increased prediction precision). It could also be used to predict excessive weight loss, which could be concerning for some patients as semaglutide 2.4 mg has improved efficacy over previous weight management medications 26 . The clinical relevance of the model is aided by its ability to predict weight loss under different dosing conditions, made possible by the inclusion of PK data during model development; for example, the model can account for treatment interruptions, as it predicted weight loss in the in‐trial analysis where treatment discontinuation and interruptions occurred, as would be expected in clinical practice.…”

“…It could also be used to predict excessive weight loss, which could be concerning for some patients as semaglutide 2.4 mg has improved efficacy over previous weight management medications. 26 The clinical relevance of the model is aided by its ability to predict weight loss under different dosing conditions, made possible by the inclusion of PK data during model development; for example, the model can account for treatment interruptions, as it predicted weight loss in the in-trial analysis where treatment discontinuation and interruptions occurred, as would be expected in clinical practice. In the future, there is potential to use model predictions to answer additional clinically relevant questions; for example, if a lower dose of semaglutide can be used to maintain body weight in individuals who reach their target weight, and if a lower dose can be used to slow the rate of weight loss in individuals with very rapid weight loss following treatment initiation.…”

Cost-effectiveness of weight-management pharmacotherapies in Canada: a societal perspective

“…The relative efficacy of other pharmacotherapies was informed via a published network meta-analysis (NMA), based on a systematic literature review conducted in September 2020 [ 45 ]. Comprehensive networks were generated by considering outcome data reported at 52–68 weeks (overall 52-week maintenance treatment across all studies after variable titration periods across trials) [ 45 ].…”

“…The relative efficacy of other pharmacotherapies was informed via a published network meta-analysis (NMA), based on a systematic literature review conducted in September 2020 [ 45 ]. Comprehensive networks were generated by considering outcome data reported at 52–68 weeks (overall 52-week maintenance treatment across all studies after variable titration periods across trials) [ 45 ]. Bayesian framework and Markov chain Monte Carlo were used and the results of fixed effects models by subpopulations with NGT, prediabetes, and T2D were used in the cost-effectiveness analysis (CEA).…”

Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high‐dose GLP‐1 receptor agonists and GLP‐1 receptor‐based co‐agonists

“… 76 A meta‐analysis of five trials that included 3642 individuals living with obesity but without T2D demonstrated that treatment with semaglutide 2.4 mg weekly was associated with a 12.3% placebo‐subtracted body weight loss (Table 3B). 75 A network meta‐analysis of semaglutide 2.4 mg for management of obesity in individuals without T2D found a greater percentage body weight loss compared to liraglutide 3.0 mg, naltrexone/buproprion, orlistat, and phentermine/topiramate 114 . The 68‐week OASIS 1 trial demonstrated that individuals with obesity who were treated with oral semaglutide 50 mg plus lifestyle intervention lost 12.7% more body weight than a group treated with placebo plus lifestyle intervention (Table 3B).…”