Treatment of Type 1 Diabetic Rats with An SGLT2 Inhibitor: Interactions with Exercise and Hypoglycemia
Greenberg, Caylee Anna
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Sodium glucose co-transporter 2 inhibitors (SGLT2i) have begun to show promise as an add-on to insulin therapy in patients with type 1 diabetes (T1D), however the effects of these drugs on plasma glucagon concentrations in T1D are not yet known. We investigated whether 8 days of SGLT2i treatment altered plasma glucagon concentrations in response to voluntary physical activity and insulin-induced hypoglycemia in male and female rats with streptozotocin-induced T1D. SGLT2 inhibition did not alter basal or post-exercise glucagon concentrations and did not affect exercise-associated changes in blood glucose levels. Additionally, SGLT2 inhibition did not affect voluntary running distance. However, in males, SGLT2 inhibition appeared to have suppressed the glucagon response to insulin-induced hypoglycemia (+40.4 48.6 pg/mL vs +22.7 30.8 pg/mL, p=0.02) and decreased the time to taken to reach hypoglycemia (63.8 17.2 min vs 30 13.4 min, p<0.0001). These results have potentially concerning implications for the use of SGLT2i in the treatment of T1D.