Effectiveness of Sodium-Glucose Transporter 2 Inhibitors and Semaglutide on Body Composition in Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Real-World Cohort Study with Bioelectrical Impedance Analysis

Abstract

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.