911-P: Effect of Dapagliflozin on Blood and Breath Ketones during Supervised Insulin Withdrawal in Adults with Type 1 Diabetes

Introduction: SGLT2 inhibitors increase DKA risk, limiting their use in T1D. To understand the effect of SGLT2i on ketone production, we measured glucose, beta-hydroxybutyrate (BOHB) and breath acetone (BrACE) with and without dapagliflozin during supervised insulin withdrawal in adults with T1D.

Methods: 20 adults with T1D underwent on-site supervised insulin withdrawal twice in a randomized crossover design: during usual care and after treatment with dapagliflozin (10 mg daily for 2 weeks plus the test day). After insulin withdrawal, capillary blood glucose, BOHB, and BrACE measurements were obtained at least hourly until stopping rules were met (glucose >400 mg/dL, BOHB >3 mmol/L, >8 hours elapsed, or participant request).

Results: Mean (± SD) age was 48 ± 18 years, with baseline HbA1c 7.0 ± 0.9%. The maximal BOHB and BrACE values achieved during supervised insulin withdrawal were both greater with dapagliflozin than usual care (BOHB: 2.4 ± 1.2 vs. 1.6 ± 1.0 mmol/L, P <0.001; BrACE: 13.7 ± 7.5 vs. 8.7 ± 5.7, P = 0.004). Adjusted for time from insulin withdrawal, dapagliflozin treatment was associated with significantly greater BOHB and BrACE concentration (both P <0.001 by ANCOVA). The proportions of participants reaching BOHB >1.5 mmol/L and >2.5 mmol/L during supervised insulin withdrawal were greater in the dapagliflozin arm (74% vs. 37% with BOHB >1.5 mmol/L; 53% vs. 16% with BOHB >2.5 mmol/L; both P <0.05 by McNemar’s test). Blood glucose reached a lower maximum (218 ± 53 vs. 302 ± 58 mg/dL, P <0.001) in the dapagliflozin arm and did not significantly change during insulin withdrawal in the dapagliflozin arm (P for linear trend = 0.91).

Conclusion: In adults with T1D undergoing up to 8 hours of supervised insulin withdrawal after dapagliflozin treatment, blood and breath ketone concentrations were significantly greater compared to usual care and in the absence of significant hyperglycemia.