Subgroup Analysis of Glycemic Outcomes in CSII Users Treated with Empagliflozin: A Subanalysis of the ENDIS Study

Subgroup Analysis of Glycemic Outcomes in CSII Users Treated with Empagliflozin: A Subanalysis of the ENDIS Study Author: Maja Navodnik Preložnik, Department of Angiology and Endocrinology, General Hospital Celje, Slovenia, et al. Date: 2025 Abstract This report presents a subgroup analysis of the ENDIS study, focusing on patients with diabetes treated with continuous subcutaneous insulin infusion (CSII). The analysis evaluated the effects of empagliflozin on glycemic outcomes after 12 weeks of treatment. A total of 28 participants were included: 16 in the empagliflozin group and 12 in the control group. Continuous variables were assessed for normality using the Shapiro–Wilk test, and between-group comparisons were performed using the Mann–Whitney U test. In the empagliflozin-treated group, HbA1c decreased significantly (7.95 → 7.50%; p < 0.05), while the control group showed a nonsignificant increase (6.85 → 7.35%; p > 0.1). Total daily insulin dose (CDO) decreased significantly in the intervention group (44.5 → 41.2 U/day; p < 0.05), whereas no significant change was observed in controls. Time in Range (TIR), glucose variability (CV%), and hypoglycemia frequency did not change significantly in either group. Serum beta-hydroxybutyrate (βOHB) levels remained stable, indicating no increased ketosis risk. All participants received education on sick-day management and ketone monitoring. Results Empagliflozin use in CSII patients resulted in a statistically significant reduction in HbA1c and total daily insulin dose without an increase in hypoglycemia or ketone formation. No significant effects were observed on Time in Range (TIR) or glucose variability (CV%). The control group demonstrated no meaningful change across measured parameters. These findings derive from the ENDIS study (Empagliflozin in Diabetes Study), conducted at the Department of Angiology and Endocrinology, General Hospital Celje, Slovenia. Parameter Empagliflozin Group (Median, Range)Control Group (Median, Range) ∆ Change p-value HbA1c (%) 7.95 → 7.50 (6.6–8.7 → 6.9–8.5) 6.85 → 7.35 (6.0–8.3 → 6.0–8.4) ↓ 0.45 vs ↑ 0.50 < 0.05 TIR (%) 67 → 69.5 (17–91 → 42–88) 79 → 71.5 (35–93 → 47–94) slight ↑ vs ↓n.s. CV (%) 31.5 → 31.0 (27–44 → 23–37) 30.2 → 31.5 (25.6–39.2 → 23–300*) ↓ 1.2 n.s. Total insulin (U/day) 44.5 → 41.2 (19–116 → 22–85) 38.9 → 41.1 (17–57 → 17–65) ↓ 7 U < 0.05 Hypoglycemia (%) 1.00 → 0.77 (0.01–3.00 → 0.01–4.00) 1.00 → 0.70 (approx.) ↓n.s. βOHB (mmol/L) 0.18 → 0.24 (0.1–0.3 → 0.1–0.7) stable – n.s. Conclusion In conclusion, this subgroup analysis from the ENDIS study demonstrates that empagliflozin treatment in patients on continuous subcutaneous insulin infusion (CSII) leads to a significant improvement in HbA1c and a reduction in total daily insulin dose, without increasing the risk of hypoglycemia or ketosis. These results support the potential role of SGLT2 inhibitors as adjunct therapy in insulin pump users when proper patient education is ensured.