Effect of SGLT2 Inhibitors on Early Metabolic Decompensation in T1D

Patients with type 1 diabetes (T1D) being treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i) are not susceptible to accelerated lipolysis and ketogenesis despite a reduction in overnight basal insulin doses, according to an open-label study published in Diabetes Technology & Therapeutics.¹

Recent reports of the increased risk for diabetic ketoacidosis with SGLT2i use in patients with T1D and type 2 diabetes have raised concerns about how treatment with SGLT2i affects the patterns of early metabolic decompensation following suspension of basal insulin.²

Researchers conducted 2 overnight pump suspension studies before and after treatment with the SGLT2i, canagliflozin, in 10 patients age 19 to 35 years with T1D for 10±8 years and a mean A1c level of 7.4%±0.8%.¹ During these studies, basal insulin was suspended at 3 AM and plasma glucose (PG), beta-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin, and glucagon were measured.

As expected, researchers observed that plasma insulin levels were decreased by 30% after treatment with canagliflozin but that baseline PG, BHB, FFA, and glucagon levels were not significantly different at the start of the suspension.¹

However, during the suspension, PG levels rose from 104±10 to 301±21 mg/dL before treatment but from only 109±8 to 195±14 mg/dL after treatment (P =.002 vs pretreatment values), and canagliflozin did not significantly affect increases in FFA, BHB, and glucagon levels. Therefore, treatment with an SGLT2i does not accelerate the rate of ketogenesis following the interruption of basal insulin infusion.

The authors concluded that, “the most important finding of this study is that clinicians and patients cannot depend on a ‘glucocentric’ approach to the early detection of infusion site failure in T1D patients on SGLT2i treatment.”¹

References

1. Patel NS, Van Name MA, Cengiz E, et al. 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;19:618-622.
2. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1687-1693.