Qing Yang,1,2 Chunmei Qin,1,2 Yanlin Lang,1,2 Wenjie Yang,3 Fenghao Yang,4 Jia Yang,1,2 Ke Liu,1,2 Jiamin Yuan,1,2 Yutong Zou,1,2 Fang Liu1,2,5 

1Department of Nephrology, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Laboratory of Diabetic Kidney Disease, Centre of Diabetes and Metabolism Research, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Department of Project Design and Statistics, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 4Department of Clinical Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 5Department of Clinical Research Management, West China Hospital of Sichuan University, Chengdu, People’s Republic of China

Correspondence: Fang Liu, Department of Nephrology, West China Hospital of Sichuan University, No. 37, Guoxue Alley, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86-18980601214, Fax +86-28-85422335, Email liufangfh@163.com

Background: Sodium-glucose transporter 2 inhibitors (SGLT-2Is) and Semaglutide may increase the risk of sarcopenia and bone fragility in vulnerable populations, yet their effects on body composition in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain unclear. This study evaluated changes in body composition by SGLT-2Is alone or combined with Semaglutide.
Methods: This retrospective cohort included T2DM-CKD patients treated with SGLT-2Is ± Semaglutide for ≥ 6 months. Body composition (fat, muscle, water, bone mineral content [BMC]) was measured via bioelectrical impedance analysis pre- and post-treatment.
Results: Among 73 participants (SGLT-2Is: n = 61; combination: n = 12), both groups showed reductions in total fat mass, total muscle mass, total body water, and BMC. Combination therapy exhibited greater fat mass loss (− 0.9 kg [IQR: − 3.7,0.4] vs − 0.6 kg [− 1.7,0.7]; P = 0.011) and muscle mass decline (− 1.1 ± 1.2 kg vs − 0.4 ± 0.8 kg; P = 0.015) versus monotherapy. Fat mass index (FMI: − 1.3 ± 2.4 kg/m² vs − 0.2 ± 0.8 kg/m²; P = 0.008) and skeletal muscle index (SMI: − 0.4 ± 0.3 kg/m² vs − 0.2 ± 0.2 kg/m²; P = 0.002) reduction were also larger with combination therapy. However, muscle mass-to-body weight percentage was increased more in the combination group (1.2 ± 2.4% vs 0.2 ± 1.2%; P = 0.041). No differences between to groups in BMC, fat percentage, or fat-to-muscle ratio (P> 0.05). Within the SGLT-2Is group, higher baseline SMI correlated with greater muscle loss, while higher baseline FMI was associated with attenuated BMC decline.
Conclusion: SGLT-2Is with/without Semaglutide reduced body composition parameters of fat, muscle, water, and BMC in T2DM-CKD. Combination therapy exacerbated absolute muscle loss but increased the muscle mass-to-body weight percentage, without significantly altering fat-to-muscle ratio. Baseline muscle and fat mass may influence treatment-related changes. Long-term studies in high-risk populations are needed.

Keywords: sodium-glucose transporter 2 inhibitors, semaglutide, type 2 diabetes mellitus, chronic kidney disease, body composition, skeletal muscle index