Enthusiasm for SGLT2 inhibitors as adjunctive agents for T1D has been tempered by increased risk of DKA, especially in pump treated patients susceptible to interruptions of basal insulin due to infusion site failures. Our insulin interruption study showed that failure to recognize early metabolic decompensation in SGLT2i-treated T1D patients relates to blunted increases in plasma glucose (PG) rather than accelerated ketogenesis (Δ PG 99±13 vs. 197±24 mg/dL, p<0.002; Δ free fatty acids [FFA] 0.8±0.1 vs. 0.7±0.1 and Δ β-hydroxy-butyrate [BHB] 1.5±0.2 vs. 1.2±0.2 mmol/L) before and after SGLT2i therapy. We report herein whether correction of early ketogenesis by a rescue dose of rapid-acting insulin is adversely affected by SGLT2i use. Ten adults [age 23±5 years, A1c 7.4±0.8%] had insulin interruption studies pre- and post 3 weeks of canagliflozin therapy. After a 6-hour suspension, a 0.2 unit/kg SQ bolus of aspart was given. PG, FFA and BHB levels were monitored for 150 minutes. PG fell from 314±42 to 183±17mg/dl pre- vs. 186±73 to 117±33mg/dL post SGLT2i use. The fall in FFA and BHB levels were unaffected by SGLT2i therapy(Figure). These data indicate that SGLT2i treatment does not impair suppression of increased FFA and BHB levels due to interruption of basal insulin infusion. Turning ketogenesis off, as well as on, does not appear to be affected by SGLT2i use.


S. Siebel: None. N.S. Patel: Consultant; Self; Janssen Pharmaceuticals, Inc.. A. Galderisi: None. L.R. Carria: None. W.V. Tamborlane: Consultant; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Medtronic MiniMed, Inc., Novo Nordisk Inc., Sanofi, Takeda Pharmaceuticals U.S.A., Inc. J. Sherr: Consultant; Self; Medtronic MiniMed, Inc.. Advisory Panel; Self; Insulet Corporation, Eli Lilly and Company, Bigfoot Biomedical.

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