Lower baseline HbA1c and reduced eGFR were associated with lower Body Recomposition Score (relatively unfavorable muscle-to-fat balance) after SGLT2 inhibitor therapy in patients with type 2 diabetes.
Key Findings
Results
Changes in body fat mass (ΔBFM) and appendicular skeletal muscle mass (ΔASM) were positively correlated with changes in body weight across all three treatment groups.
This relationship held in the SGLT2i group (n=36), GLP-1RA group (n=17), and GLP-1RA add-on to SGLT2i group (n=20).
Body composition was assessed using bioelectrical impedance analysis at 12 months after treatment initiation.
The finding indicates that overall weight change drives both fat and muscle changes regardless of drug class.
Results
ΔASM and ΔBFM were positively correlated only in the GLP-1RA group, but not in the SGLT2i or GLP-1RA add-on to SGLT2i groups.
This differential correlation pattern suggests interindividual heterogeneity in muscle-to-fat balance changes specific to treatment type.
The absence of correlation in the SGLT2i group indicates that muscle and fat mass changes were dissociated from one another, supporting variable body recomposition outcomes.
The GLP-1RA group (n=17) showed a coupled relationship between muscle and fat loss, while SGLT2i users showed more variable patterns.
Results
In the SGLT2i group, the Body Recomposition Score (BRS) was positively correlated with both baseline HbA1c and estimated glomerular filtration rate (eGFR).
BRS was defined as ΔASM − ΔBFM; BRS < 0 was operationally defined as indicating relatively unfavorable body recomposition.
Correlation with baseline HbA1c: r = 0.36, p = 0.029.
Correlation with baseline eGFR: r = 0.34, p = 0.040.
No baseline variables were significantly correlated with BRS in the GLP-1RA or GLP-1RA add-on to SGLT2i groups.
Results
Exploratory ROC analyses identified Youden index-derived cut-off values for discriminating BRS < 0 in the SGLT2i group.
The cut-off for baseline HbA1c was 6.6%.
The cut-off for baseline eGFR was 65 mL/min/1.73 m².
These cut-offs were derived from receiver operating characteristic analyses in the primary SGLT2i cohort (n=36) and are described as exploratory.
Results
Findings from the primary cohort were externally assessed in an independent cohort of 148 patients with type 2 diabetes receiving SGLT2i therapy.
In the external cohort, BRS was calculated as change in total skeletal muscle mass (ΔSMM) − ΔBFM at 4 weeks after SGLT2i initiation.
BRS showed significant positive correlations with both baseline HbA1c and eGFR in the external cohort.
This external assessment provided supporting evidence for the associations identified in the primary cohort.
Results
Lower baseline HbA1c and reduced eGFR were associated with lower BRS (relatively unfavorable body recomposition) after SGLT2i therapy.
Patients with lower HbA1c at baseline had BRS values below the identified cut-off of 6.6%, indicating relatively unfavorable muscle-to-fat balance changes.
Patients with eGFR below 65 mL/min/1.73 m² were associated with BRS < 0.
The authors characterize these as 'exploratory findings' supporting individualized pharmacotherapy in type 2 diabetes with consideration of muscle-to-fat balance.
This was a multicenter retrospective cohort study with 12-month follow-up for the primary cohort.
What This Means
This research examined how two classes of diabetes medications — SGLT2 inhibitors (like empagliflozin or dapagliflozin) and GLP-1 receptor agonists (like semaglutide) — affect the balance between muscle and fat in people with type 2 diabetes. The researchers tracked 73 patients over 12 months and used a scoring system called the Body Recomposition Score (BRS) to capture whether patients were relatively preserving muscle while losing fat (favorable) or losing more muscle relative to fat (unfavorable). An additional group of 148 patients was used to check whether the main findings held up in a separate dataset.
The study found that among patients taking SGLT2 inhibitors, those who started with lower blood sugar control (lower HbA1c) or reduced kidney function (lower eGFR) tended to have worse body recomposition outcomes — meaning they lost relatively more muscle compared to fat. Specific threshold values were identified: a baseline HbA1c below about 6.6% and an eGFR below 65 mL/min/1.73 m² were associated with less favorable muscle-to-fat balance changes. These patterns were not seen in patients taking GLP-1 receptor agonists, suggesting the two drug classes may affect body composition differently.
This research suggests that not everyone starting SGLT2 inhibitor therapy may experience the same body composition benefits, and that individual factors like kidney function and baseline blood sugar levels may influence outcomes. The authors emphasize that these are exploratory findings and call for individualized treatment decisions that consider muscle preservation alongside weight and blood sugar management, particularly for patients who already have modest glycemic control or reduced kidney function.
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Gobaru M, Hasuzawa N, Kurinami N, Wada N, Wang L, Nagayama A, et al.. (2026). Low baseline HbA1c and reduced eGFR are associated with relatively unfavorable body recomposition after SGLT2 inhibitor therapy in type 2 diabetes.. Frontiers in endocrinology. https://doi.org/10.3389/fendo.2026.1924744