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

Diabetes Technol Ther. 2017 Nov;19(11):618-622. doi: 10.1089/dia.2017.0267. Epub 2017 Oct 25.


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.

MeSH terms

  • Adolescent
  • Adult
  • Blood Glucose / analysis*
  • Canagliflozin / administration & dosage
  • Canagliflozin / therapeutic use*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Fatty Acids, Nonesterified / blood
  • Female
  • Glucagon / blood
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / administration & dosage
  • Insulin / blood*
  • Insulin Infusion Systems
  • Male
  • Middle Aged
  • Sodium-Glucose Transporter 2 Inhibitors*
  • Young Adult


  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Hypoglycemic Agents
  • Insulin
  • Sodium-Glucose Transporter 2 Inhibitors
  • Canagliflozin
  • Glucagon