269-OR: Effect of Insulin Degludec on Frequency of Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia: The HypoDeg Trial

Abstract

Background and Aims: The long-acting insulin analog degludec reduces the risk of nocturnal hypoglycemia in patients with type 1 diabetes (T1D). The HypoDeg trial compared the effect of insulin degludec to insulin glargine U100 on frequency of nocturnal hypoglycemia in T1D patients with recurrent nocturnal severe hypoglycemia and reported a significant 37% relative risk reduction (RRR) of symptomatic nocturnal hypoglycemia ≤ 3.0 mmol/L with insulin degludec. Here we report the data on severe hypoglycemia (SH). Materials and Methods: In this investigator-initiated, prospective, randomized, open-label, blinded-endpoint crossover trial conducted at 10 centers in Denmark, we recruited 149 T1D patients (>18 years) with ≥2 episodes of nocturnal SH in the preceding two year. Patients were randomly assigned (1:1) to basal-bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. A 1-year plus 1-year treatment period was specified, consisting of two 3-month run-in periods, each followed by a 9-month maintenance period. Episodes of SH were reported by telephone and adjudicated blinded to treatment. Results: A total of 136 SH episodes were reported during the maintenance periods: 56 (41%) episodes during treatment with insulin degludec and 80 (59%) episodes during treatment with insulin glargine U100, resulting in a RRR of 35% (95% confidence interval [CI]: 0-60%; p=0.04). This corresponds to an absolute rate reduction of 0.3 episodes (95% CI: 0.0-0.5) per patient-year with insulin degludec. The difference was primarily due to a lower risk of nocturnal episodes (RRR 52%, 95% CI: -10-80%; p=0.08), whereas there was no difference during daytime (RRR 10%, 95% CI: -80-50%; p=0.75). Conclusion: Treatment with insulin degludec in T1D patients with recurrent nocturnal SH resulted in a clinically significant reduced rate of SH compared with insulin glargine U100. Disclosure R.M. Agesen: Employee; Self; Novo Nordisk A/S. A. Alibegovic: Employee; Self; Novo Nordisk A/S. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi-Aventis. T.K. Hansen: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C.B. Juhl: None. A.K. Jensen: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. H.D. Parving: None. A.L. Sørensen: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S