Frontiers in endocrinology · 2026
Low baseline HbA1c and reduced eGFR are associated with relatively unfavorable body recomposition after SGLT2 inhibitor therapy in type 2 diabetes.
СтатьяМногоцентровое исследованиеНаблюдательное исследованиеНазвание и аннотация: Перевод в очереди
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Gobaru Mizuki, Hasuzawa Nao, Kurinami Noboru, Wada Nobuhiko, Wang Lixiang, Nagayama Ayako, Ashida Kenji, Moriyama Yoshinori, Jinnouchi Hideaki, Nomura Masatoshi
Аннотация
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 m2 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.
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 m2 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.