GLP-1 weight loss is driven mainly by fat loss, not muscle loss

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Apr 27 2026

A systematic review and meta-analysis finds that GLP-1-based treatments drive clinically meaningful weight loss mainly through fat reduction, but experts warn that preserving muscle remains essential for long-term metabolic health.

Review: GLP-1 agonists and changes in body mass and composition in adults with overweight or obesity with or without type 2 diabetes mellitus: a systematic review and meta-analysis. Image Credit: Love Employee / Shutterstock

In a recent study published in the International Journal of Obesity, researchers assessed the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) agonists on weight and body composition in adults with overweight or obesity.

GLP-1 Therapy and Obesity Treatment Background

The prevalence of obesity has markedly increased worldwide over the past decades. Obesity is associated with several cardiometabolic complications, which reduce the quality of life as well as life expectancy. As such, effective management of obesity requires a personalized, multidisciplinary approach combining behavioral and dietary interventions, pharmacological therapies, physical activity, and surgery.

GLP-1RAs and related incretin-based therapies contribute to sustained weight loss in obese individuals, which is accompanied by improvements in related comorbidities. GLP-1RAs have also shown cardioprotective properties. While these medications primarily reduce fat body mass (FBM), loss of lean body mass (LBM) can also occur, raising concerns about muscle loss in susceptible populations, such as frail individuals and older adults.

GLP-1 Body Composition Meta-Analysis Methods

In the present study, researchers evaluated the efficacy of GLP-1RAs and dual GLP-1/GIP agonists in modulating body composition and promoting weight loss in adults with overweight or obesity with or without type 2 diabetes (T2D). First, Web of Science, PubMed, and Scopus databases were comprehensively searched for clinical studies assessing the effects of GLP-1-based therapies on anthropometric indices and body composition in the specified populations. After deduplication, abstracts/titles and full-texts were assessed for inclusion.

The Study Quality Assessment Tools were used to evaluate methodological quality. Meta-analyses were performed on eligible studies that presented numerical data on the changes in select body composition and anthropometric parameters with GLP-1-based treatment. Data were pooled using random-effects models, and subgroup analyses were performed by drug type and treatment duration. Publication bias was assessed using Egger’s test.

In total, 36 studies were included in the qualitative analysis and 24 in the meta-analyses. Most studies were conducted in Europe and Asia, and most reported outcomes after 6 months of treatment. Twenty-four studies included individuals with T2D. Liraglutide and semaglutide were the most frequently investigated GLP-1RAs. The included studies varied in design, populations, drug regimens, treatment duration, and body-composition methods. Bioelectrical impedance analysis and dual-energy x-ray absorptiometry were the most common methods to assess body composition.

Weight Loss and Lean Mass Findings

Significant improvements in body composition and anthropometric parameters were observed after GLP-1-based treatment. At three months, a significant 9% reduction in body mass was observed, especially in beinaglutide recipients, with marked decreases in visceral adipose tissue (VAT) area (−29.25 cm²) and FBM (−17%). A modest but significant LBM loss (−2%) also occurred. Body mass index (BMI) and waist circumference (WC) also decreased by 2.96 kg/m² and 9.6 cm, respectively.

At six months, body mass was significantly decreased by 5%, and both FBM and LBM showed significant reductions of 6% and 1%, respectively. BMI decreased by 2.40 kg/m², while WC showed a modest reduction (−2.3 cm). Moreover, a significant 3% reduction in skeletal muscle mass was observed. There was also a significant decrease in the VAT area (−32.31 cm²).

At 12 months, body mass decreased by 4%, WC decreased by 3.2 cm, and BMI decreased by 1.74 kg/m². The largest reductions were reported in a liraglutide study, although the authors noted substantial interstudy variability and cautioned against overinterpreting agent-specific differences. Further, FBM and LBM were significantly reduced by 4%. Egger’s test revealed significant publication bias for some outcomes at three months, with no evidence of bias for most outcomes at other time points.

Clinical Implications for Fat Loss and Muscle Preservation

Together, the findings illustrate the substantial efficacy of GLP-1-based therapies on anthropometric indices associated with obesity. Body mass, BMI, and WC showed significant reductions at 3, 6, and 12 months of treatment. The most substantial and rapid changes occurred in the first three months, especially with beinaglutide in terms of BMI and weight reduction. Specifically, body mass decreased by 9% after three months, 5% after six months, and 4% after 12 months.

GLP-1-based therapies led to favorable changes in body composition, with significant reductions in VAT and FBM, particularly during the first six months. While LBM loss was evident, it was relatively modest compared to body mass loss.

The authors characterized this pattern as “quality” weight loss, driven mainly by fat mass reduction with relative preservation of lean tissue. Notably, no single GLP-1RA was superior to the others in preserving lean mass.

Future studies should explore more effective combinations of lifestyle interventions and pharmacotherapy, with emphasis on maintaining metabolic health and preserving lean mass, particularly through nutritional support and resistance training, among people at higher risk of sarcopenia.