Effect of short-term use of dapagliflozin on impaired awareness of hypoglycaemia in people with type 1 diabetes.

Impaired awareness of hypoglycaemia (IAH) affects about 25% of patients with type 1 diabetes (T1DM). IAH can be reversed by strict avoidance of hypoglycaemia for at least 3 weeks. Adjunctive treatment with sodium glucose cotransporter 2 inhibitors may reduce the risk of hypoglycaemia through reduction of glucose variability. We tested the hypothesis that short-term use of dapagliflozin may improve awareness of hypoglycaemia in people with T1DM and IAH. Fifteen patients with T1DM and IAH were included in this randomized double-blind, placebo-controlled cross-over trial (age 49.7 ± 14.6 years, 40% men, disease duration 24.1 ± 14.2 years, glycated haemoglobin 7.5 ± 0.8% (58.6 ± 8.4 mmol/mol). They were treated with dapagliflozin 10 mg once daily or matching placebo, with a washout period of 2 weeks. At the end of each treatment period, participants underwent a modified hyperinsulinaemic normoglycaemic-hypoglycaemic glucose clamp (glucose nadir 2.5 mmol/L). Blinded continuous glucose monitors were used in the final treatment weeks. Treatment with dapagliflozin significantly improved glycated haemoglobin [-0.32 ± 0.10 vs. 0.22 ± 0.13% (-4.1 ± 0.9 vs. 2.3 ± 1.4 mmol/mol), dapagliflozin vs. placebo, p = .007] and glucose variability (standard deviation, 2.6 ± 0.2 vs. 3.1 ± 0.3 mmol/L, p = .029), but did not affect the frequency of hypoglycaemia. During the hypoglycaemic clamp, dapagliflozin did not affect symptom responses (8.0 ± 3.4 vs. 5.2 ± 1.6, p = .31), but significantly reduced the need for exogenous glucose to maintain hypoglycaemia (3.2 ± 0.3 vs. 4.1 ± 0.4 mg/kg/min, p = .022). Eight weeks of treatment with dapagliflozin did not restore hypoglycaemic awareness in people with T1DM and impaired awareness of hypoglycaemia, but ameliorated some clinical aspects.

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© 2021 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.