A systematic review of the effect of semaglutide on lean mass: insights from clinical trials

ABSTRACT

Introduction

Semaglutide, a glucagon-like peptide-1 receptor agonist, is associated with significant weight loss, yet its impact on lean body mass remains insufficiently understood. This review investigates the effect of semaglutide on lean mass in the context of obesity management.

Methodology

This study investigates through different databases (PubMed, Elsevier, and Google Scholar) from 2016 for randomized control trials (RCTs) or observational studies that assessed the use of semaglutide in overweight or obese patients, regardless of whether they have type 2 diabetes or not. The studies compared semaglutide to a placebo or alternative medications.

Results

Six studies with 1,541 overweight or obese adults were included, and significant weight reductions were observed primarily due to fat mass loss. While the lean mass remained stable in some cases, notable reductions ranging from almost 0% to 40% of total weight reduction were observed in others. Noteworthy decreases in lean mass were particularly evident in larger trials, yet the proportion of lean mass relative to total body mass increased, suggesting a positive overall outcome.

Conclusion

Semaglutide displays potential for weight loss primarily through fat mass reduction. However, concerns arise from notable reductions in lean mass, especially in trials with a larger number of patients.

KEYWORDS:

• Muscle loss
• lean mass loss
• semaglutide
• glucagon-like peptide-1 receptor agonist
• weight loss

Article highlights

• Investigation of semaglutide’s impact on lean mass in obesity management.

• Reviewed six studies comprising 1,541 overweight or obese adults.

• Significant weight reductions observed, primarily attributed to fat mass loss.

• Notable reductions in lean mass observed in larger trials, ranging from 0% to 40% of total weight reduction.

• Despite reductions, the proportion of lean mass relative to total body mass increased, suggesting a positive outcome.

• Findings suggest potential concerns regarding notable reductions in lean mass, particularly in trials with larger patient cohorts.

• Importance of incorporating muscle mass and function as key endpoints in future clinical trials assessing weight-loss treatment.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/14656566.2024.2343092

Additional information

Funding

This paper was not funded.