{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T05:18:39Z","timestamp":1787807919679,"version":"build-2784847793"},"reference-count":25,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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 (\u0394ASM) and body fat mass (\u0394BFM) were assessed using bioelectrical impedance analysis. The Body Recomposition Score (BRS) was defined as \u0394ASM \u2212 \u0394BFM and used as an exploratory index of the relative balance between muscle and fat mass changes; BRS &amp;lt; 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      \u0394BFM and \u0394ASM were positively correlated with changes in body weight (\u0394BW) in all treatment groups. However, \u0394ASM and \u0394BFM 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 &amp;lt; 0 in the SGLT2i group: 6.6% for baseline HbA1c and 65 mL\/min\/1.73 m\n                      <jats:sup>2<\/jats:sup>\n                      for eGFR. In the external cohort, BRS, calculated as the change in total skeletal muscle mass (\u0394SMM) \u2212 \u0394BFM at 4 weeks after SGLT2i initiation, showed significant positive correlations with baseline HbA1c and eGFR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:related-object>\n                      <jats:ext-link>https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000055239<\/jats:ext-link>\n                      , identifier UMIN000048469;\n                      <jats:ext-link>https:\/\/center6.umin.ac.jp\/cgi-open-bin\/ctr_e\/ctr_view.cgi?recptno=R000055242<\/jats:ext-link>\n                      , identifier UMIN000048471.\n                    <\/jats:related-object>\n                  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