Dionysus or apollo, skeletal muscle mass changes in type 2 diabetes with sarcopenia receiving GLP-1 receptor agonist: systematic review and meta-analysis

Abstract

Objective: Type 2 diabetes mellitus (T2DM) increases the risk of sarcopenia, but evidence on the effects of glucagon-like peptide 1 receptor agonist (GLP-1 RA) in skeletal muscle is limited and inconsistent. The study aimed to evaluate the skeletal muscle mass of GLP-1 RA in patients with type 2 diabetes.

Methods: Randomized controlled trials of GLP-1 RA for sarcopenia with type 2 diabetes were identified by searching databases (up to July 6, 2025). Electronic databases (CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane library, Web of Science, and Google Scholar), grey literature (Open Grey and Proquest) and reference lists of included articles were searched. The I² and τ² statistic was used to assess the heterogeneity. The random effects model was applied regardless of the heterogeneity. Funnel plots were used to assess publication bias. The results were evaluated by calculating the risk ratio (RR), mean difference (MD), and confidence interval (CI).

Results: The study included nine randomized controlled trials with a total of 1089 participants. GLP-1 RA significantly reduced weight-related changes and fat-related changes, including body weight (BW) (MD= -2.25, 95%CI: -6.99 to 1.89 P = 0.20), body mass index (BMI) (MD= -1.83, 95%CI: -3.88 to 0.23, P < 0.01), fat mass (FM) (MD= -8.00, 95%CI: -11.93 to -4.08, P < 0.01), body fat ratio (BFR) (MD= -2.76, 95%CI: -3.65 to -1.87, P < 0.01), visceral fat area (VFA) (MD = 0.74, 95%CI: -54.93 to 56.40, P < 0.05). In muscle-related changes, lean body mass (LBM) (MD = 4.61, 95%CI: -4.19 to 13.42, P = 0.31), and skeletal muscle index (SMI) (MD = 0.59, 95% CI: -0.69 to 1.86, P = 0.19) were not significantly different.

Conclusion: GLP-1 receptor agonists, regardless of structure, have beneficial effects on body weight and fat content in type 2 diabetes with sarcopenia, but have no effect on reducing muscle mass.

Registration: PROSPERO (CRD42023473528).

Keywords: Glucagon-like peptide 1 receptor agonist; Meta-analysis; Sarcopenia; Skeletal muscle mass; Type 2 diabetes.

Fig. 1

Flow chart of literature search and study selection

Fig. 2

Risk of bias: (A) Risk of bias summary about each risk of bias item for each included study. (B) Risk of bias graph about each risk of bias item presented as percentages across all included studies

Fig. 3

The association between GLP-1 RA and muscle changes: (A) muscle mass (LBM), (B) skeletal muscle index (SMI)

Fig. 4

The association between GLP-1 RA and weight changes: (A) body weight (BW), (B) body mass index (BMI)

Fig. 5

The association between GLP-1 RA and fat changes: (A) body fat mass (FM), (B) fat weight% (BFR), (C) visceral fat interval (VFA)

Fig. 6

Forest plot of incidence of adverse events between the two groups