SGLT Inhibition: A Novel Approach to Reducing Hypoglycemia in T1D Diabetes

Poster Title: SGLT Inhibition: A Novel Approach to Reducing Hypoglycemia in T1D

Student: Daniel Ines, Class of 2025

Faculty Mentor and Department: Schafer Boeder, MD, Division of Endocrinology, Diabetes, and Metabolism

Funding Source: None

ABSTRACT

Background: Individuals with T1D have an ineffective glucagon response to low glucose levels which predisposes them to episodes of hypoglycemia. SGLT-2 inhibitors (SGLT2i) do not increase and may even reduce hypoglycemia in clinical trials, yet the mechanism is unknown.

Hypothesis: This trial was conducted to determine if SGLT2i improves the counterregulatory response (CR) to hypoglycemia.

Methods: Subjects with T1D (n=22) received 4 weeks of SGLT2i (dapagliflozin 5 mg daily) and 4 weeks of placebo in a double-blind, random-order, cross-over study.  After each phase, subjects underwent a hypoglycemic clamp. During 40 min of hypoglycemia (mean serum glucose 49 mg/dL) CR hormones were serially measured.

Results: There was no difference between treatment phases in glucagon or other CR hormones during hypoglycemia. Mean ± SE (paired two-tailed t-test) during hypoglycemia for SGLT2i vs Placebo were: Glucagon (15.4 ± 1.8 vs 14.8 ± 2.1 pg/mL; P = 0.77), Epinephrine (216 ± 34 vs 200 ± 28 pg/mL; P = 0.46), Norepinephrine (402 ± 39 vs 381 ± 25 pg/mL; P = 0.51), GH (9.1 ± 1.3 vs 8.4 ± 1.8 ng/mL; P = 0.60), and Cortisol (11.4 ± 1.1 vs 10.3 ± 0.9 mcg/dL; P = 0.18).

Conclusions: SGLT2i treatment has no effect on the CR hormone response to hypoglycemia in T1D.  These data suggest that any reduction in hypoglycemia that occurs with these agents may be due to behavioral changes (e.g., lower insulin doses, less frequent bolusing), rather than a physiologic mechanism.   

Source of mentor’s funding or other support that funded this research: JDRF Grant, Dexcom Inc, REMD Biotherapeutics