Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Characterizing the Effects of Using GLP-1 Receptor–Based Agonists on Body Composition
TAKE-HOME MESSAGE
- This study assessed data regarding the effects of GLP-1 receptor–based agonists on body composition. Patients using these agonists experienced greater reductions in fat mass than controls (weighted mean difference [WMD], −2.25 kg). Patients with diabetes showed a more significant fat mass reduction (WMD, −3.68 kg) than those without diabetes (WMD, −0.33 kg). However, fat mass percentage changes were comparable between the two groups. Subgroup analyses indicated significant fat mass reductions in patients using liraglutide (WMD, −2.40 kg), semaglutide (WMD, −3.80 kg), and tirzepatide (WMD, −9.60 kg). These treatments also resulted in notable reductions in visceral and subcutaneous fat areas. A modest reduction in lean body mass was observed (WMD, −1.02 kg), with comparable reductions between patients with and without diabetes. Notably, greater waist and hip circumference reductions were correlated with more significant lean mass losses.
- Studying the effects of GLP-1 receptor agonists on muscle function is crucial. For patients at high risk of sarcopenia, careful consideration should be given to initiating GLP-1 receptor agonist therapy after a thorough individual assessment.
abstract
This abstract is available on the publisher's site.
Access this abstract nowAIM
Diabetes is an independent risk factor for muscle mass loss, with possible mechanisms including impaired insulin signalling and chronic inflammation. The use of a glucagon-like peptide 1 (GLP-1) receptor-based agonist could lead to weight reduction, which might result from the loss of both fat and skeletal muscle. However, the body composition-modifying effects of GLP-1 receptor-based agonists have not been systematically characterized.
METHODS
PubMed, EMBASE, the Cochrane Center Register of Controlled Trials for Studies and Clinicaltrial.gov were searched from inception to October 2023. Randomized controlled trials of GLP-1 receptor agonist or glucose-dependent insulinotropic polypeptide/GLP-1 receptor dual agonist, which reported the changes of body composition, were included. The results were computed as weighted mean differences (WMDs) and 95% confidence intervals (CIs) in a random-effects model.
RESULTS
In all, 19 randomized controlled trials were included. When compared with controls, substantial reductions in fat body mass were observed in patients using GLP-1 receptor-based agonist treatment (WMD = -2.25 kg, 95% CI -3.40 to -1.10 kg), with decrease in areas of both subcutaneous fat (WMD = -38.35 cm2, 95% CI, -54.75 to -21.95 cm2) and visceral fat (WMD = -14.61 cm2, 95% CI, -23.77 to -5.44 cm2). Moreover, greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users compared with non-users (WMD = -1.02 kg, 95% CI, -1.46 to -0.57 kg), while the changes in lean mass percentage were comparable between GLP-1 receptor-based agonist users and non-users.
CONCLUSION
Compared with the controls, GLP-1 receptor-based agonist users experienced greater reductions in fat body mass, with body shaping effects in terms of both subcutaneous fat mass and visceral fat mass. Although greater reductions in lean body mass were also observed in GLP-1 receptor-based agonist users, the changes in lean mass percentage were comparable between the users and non-users.
Additional Info
Disclosure statements are available on the authors' profiles:
Characterizing body composition modifying effects of a glucagon-like peptide 1 receptor-based agonist: A meta-analysis
Diabetes Obes Metab 2024 Oct 21;[EPub Ahead of Print], R Jiao, C Lin, X Cai, J Wang, Y Wang, F Lv, W Yang, L JiFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Weight loss in people with obesity reduces fat mass but also reduces fat-free mass. About half of fat-free mass is accounted for by skeletal muscle; however, fat-free mass also includes organs, body fluids, skin, and other tissues. The reduction in fat-free mass accounts for approximately 25% of total weight loss on average in studies of weight loss achieved through behavioral or surgical interventions. However, it remains uncertain whether weight loss achieved by GLP-1 receptor agonist or GLP-1/GIP dual receptor agonist (GLP-1 RA) therapy is associated with a disproportionate loss of fat-free mass. Because skeletal muscle mass is a major determinant of basal metabolic rate and is protective against frailty, there is intense interest in understanding the impact of these highly effective obesity pharmacotherapies on body composition.
This meta-analysis included 19 randomized controlled trials of GLP-1 RA treatment that reported changes in body composition. The purpose of the meta-analysis was to characterize the body composition–modifying effects of GLP-1 RA treatment. The results showed that GLP-1 RA treatment significantly reduced fat mass (weighted mean difference = −2.25 kg; 95% CI, −3.40 to −1.10 kg) and lean body mass (weighted mean difference = −1.02 kg; 95% CI, −1.46 to −0.57 kg) but did not significantly affect the change in lean mass percentage. Unexpectedly, no reduction in fat mass was observed in the analysis of GLP-1 RA trials in patients without diabetes — a result generated because no studies of semaglutide or tirzepatide were included in the analysis. Indeed, only 2 of the 19 trials and 104 of the 1345 participants included in the full meta-analysis used semaglutide or tirzepatide; most of the trials studied liraglutide or exenatide.
This meta-analysis highlights the absence of rigorous body composition data associated with weight loss achieved by using the highly effective GLP-1 receptor-based agonists semaglutide and tirzepatide. Future studies should aim to close this knowledge gap while also quantifying the changes in physical function that result from clinically significant weight loss.