Journal of Obesity & Metabolic Syndrome · Mar 3, 2026

Metabolic Impact of Sodium-Glucose Cotransporter 2 Inhibitor-Induced Ketogenesis in Type 2 Diabetes Mellitus

By Park HW, Choe HJ, Lim HJ et al.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control and confer cardiovascular and renal benefits in individuals with type 2 diabetes mellitus (T2DM) partly by promoting urinary glucose excretion and modulating energy metabolism. However, the clinical relevance of ketogenesis induced by SGLT2 inhibitors remains unclear. METHODS: This retrospective cohort study was conducted at the Seoul National University Bundang Hospital, South Korea. In total, 151 adults with T2DM who were newly treated with SGLT2 inhibitors (empagliflozin or dapagliflozin) between November 2021 and June 2024 were enrolled. Glycemic parameters (glycosylated hemoglobin [HbA1c], body mass index [BMI], and fasting plasma glucose [FPG]) as well as metabolic profiles (lipid profile, renal function, and hepatic function) were assessed at baseline and after 6 months of treatment. The participants were stratified into tertiles based on the relative increase in serum ketone levels. RESULTS: SGLT2 inhibitor treatment significantly improved HbA1c, FPG, BMI, insulin sensitivity, and the lipid profile. Mean serum ketone levels increased from 92.7±69.4 to 173.5±172.6 μmol/L (P<0.001), although with substantial inter-individual variability. Although ketone elevation did not independently predict HbA1c reduction, participants with elevated ketone responses exhibited enhanced FPG reduction, higher urinary glucose excretion, and favorable triglyceride reduction, suggesting metabolic benefits. A moderate decline in kidney function was also observed in these participants. CONCLUSION: Ketogenesis did not independently predict HbA1c reduction; however, elevated ketone levels following SGLT2 inhibitor treatment were associated with favorable metabolic adaptations, suggesting potential extra-glycemic benefits.

doi.org/10.7570/jomes25062 Open access PubMed 41771543 Interventions