Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study

Abstract

Background: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin.

Methods: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7.4% ± 0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), β-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6 h after suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L.

Results: PI levels at the start of suspension were reduced by 30% after CANA treatment (44 ± 11 uU/mL vs. 31 ± 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels were not significantly different. During the suspension, PG rose from 104 ± 10 to 301 ± 21 mg/dL before treatment, but only from 109 ± 8 to 195 ± 14 mg/dL after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA treatment did not significantly affect the magnitude of increases in FFA, BHB, and glucagon levels during the suspension study.

Conclusion: These data indicate that SGLT2i do not accelerate the rate of ketogenesis following the interruption of basal insulin infusion in T1D. Rather, the failure of patients to promptly recognize early metabolic decompensation relates to the much more gradual rise in PG levels.

Keywords: Glucose levels; Ketosis; Pump failure; SGLT2 inhibitor; Type 1 diabetes.

Conflict of interest statement

W.V.T. is a consultant for AstraZeneca, Boehringer Ingelheim, Janssen, Medtronic Diabetes, NovoNordisk, and Sanofi. S.A.W. is a consultant and speaker for Insulet and receives research grant support from Medronic (to Yale). E.C. is a speaker for NovoNordisk and on advisory board of Novo, Mannkind, Adocia, and Lexicon. J.L.S. serves on the advisory board of Bigfoot Biomedical and Insulet and is a consultant for Medtronic Diabetes. No other potential conflicts of interest relevant to this article were reported. No sponsor had any role in the study design, data collection, data analysis, data interpretation, or writing of the report.

Figures

FIG. 1.

Plasma glucose and BHB levels during the control and CANA treatment studies. Changes in plasma glucose (top) and β-hydroxybutyrate (bottom) are shown during suspension. Control condition is depicted as dotted line with circles, CANA condition as solid line with squares. BHB, β-hydroxybutyrate; CANA, canagliflozin.