Low baseline HbA1c and reduced eGFR are associated with relatively unfavorable body recomposition after SGLT2 inhibitor therapy in type 2 diabetes

Vollständiger Abstract

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Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycemic control and promote weight loss, but their effects on the relative balance between skeletal muscle and fat mass remain incompletely understood. This study examined treatment-associated body composition changes in patients with type 2 diabetes mellitus (T2DM), focusing on muscle-to-fat balance. Methods In this multicenter retrospective cohort study, we analyzed body composition changes 12 months after initiation of SGLT2i (n = 36), GLP-1RA (n = 17), or GLP-1RA add-on to SGLT2i therapy (n = 20). Changes in appendicular skeletal muscle mass (ΔASM) and body fat mass (ΔBFM) were assessed using bioelectrical impedance analysis. The Body Recomposition Score (BRS) was defined as ΔASM − ΔBFM and used as an exploratory index of the relative balance between muscle and fat mass changes; BRS < 0 was operationally defined as indicating relatively unfavorable body recomposition. An independent external cohort of patients with T2DM (n = 148) was used for external assessment. Results ΔBFM and ΔASM were positively correlated with changes in body weight (ΔBW) in all treatment groups. However, ΔASM and ΔBFM were positively correlated only in the GLP-1RA group, whereas no such correlation was observed in the SGLT2i or GLP-1RA add-on to SGLT2i groups, suggesting interindividual heterogeneity in muscle-to-fat balance changes. In the SGLT2i group, BRS was positively correlated with baseline HbA1c (r = 0.36, p = 0.029) and estimated glomerular filtration rate (eGFR; r = 0.34, p = 0.040). No baseline variables correlated significantly with BRS in the other groups. Exploratory receiver operating characteristic analyses identified Youden index-derived cut-offs for discriminating BRS < 0 in the SGLT2i group: 6.6% for baseline HbA1c and 65 mL/min/1.73 m 2 for eGFR. In the external cohort, BRS, calculated as the change in total skeletal muscle mass (ΔSMM) − ΔBFM at 4 weeks after SGLT2i initiation, showed significant positive correlations with baseline HbA1c and eGFR. Conclusions Lower baseline HbA1c and reduced eGFR were associated with lower BRS after SGLT2i therapy in patients with T2DM. These exploratory findings support the importance of individualized pharmacotherapy for type 2 diabetes with consideration of muscle-to-fat balance. Clinical trial registration https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055239 , identifier UMIN000048469; https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000055242 , identifier UMIN000048471.