Julie Maria Bøggild Brøsen1,2, Rikke Mette Agesen1,2,3, Amra Ciric Alibegovic3,4, Henrik Ullits Andersen2,4, Henning Beck-Nielsen5,6, Peter Gustenhoff7, Troels Krarup Hansen8,9, Christoffer Georg Riber Hedetoft10, Tonny Joran Jensen2,11, Charlotte Røn Stolberg5,12,13, Claus Bogh Juhl12,13,14, Susanne Søgaard Lerche15, Kirsten Nørgaard2,4,16, Hans-Henrik Parving2,11, Lise Tarnow17,18, Birger Thorsteinsson1,2, Ulrik Pedersen-Bjergaard1,2. 1. Department of Endocrinology and Nephrology, Copenhagen University Hospital - North Zealand, Hillerød, Denmark. 2. Department of Clinical Medicine, Faculty of Health and Medical & Sciences, University of Copenhagen, Denmark. 3. Department of Medical & Science, Novo Nordisk A/S, Søborg, Denmark. 4. Steno Diabetes Center Copenhagen, Herlev, Denmark. 5. Department of Endocrinology, Odense University Hospital, Odense, Denmark. 6. Department of Regional Health Research, Faculty of Health and Sciences, University of Southern Denmark, Odense, Denmark. 7. Steno Diabetes Center North, Aalborg, Denmark. 8. Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 9. Steno Diabetes Center Aarhus, Aarhus, Denmark. 10. Department of Internal Medicine, Zealand University Hospital, Køge, Denmark. 11. Department of Medical Endocrinology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark. 12. Department of Medicine, University Hospital South West Jutland, Esbjerg, Denmark. 13. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. 14. Steno Diabetes Center Odense, Odense, Denmark. 15. Department of Diabetes and Hormonal Diseases, Lillebælt Hospital Kolding, Denmark. 16. Department of Endocrinology, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark. 17. Department of Clinical Research, Copenhagen University Hospital - North Zealand, Hillerød, Denmark. 18. Steno Diabetes Center Zealand, Holbæk, Denmark.
Abstract
Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).
Background and Aims: Nocturnal hypoglycemia is mainly a consequence of inappropriate basal insulin therapy in type 1 diabetes (T1D) and may compromise optimal glycemic control. Insulin degludec is associated with a lower risk of nocturnal hypoglycemia in T1D. As nocturnal hypoglycemia is often asymptomatic, we applied continuous glucose monitoring (CGM) to detect a more precise occurrence of nocturnal hypoglycemia in the HypoDeg trial, comparing insulin degludec with insulin glargine U100 in people with T1D and previous nocturnal severe hypoglycemia. Materials and Methods: In the HypoDeg trial, 149 people with T1D were included in an open-label randomized cross-over trial. Sixty-seven participants accepted optional participation in the predefined substudy of 4 × 6 days of blinded CGM requiring completion of at least one CGM period in each treatment arm. CGM data were reviewed for hypoglycemic events. Results: Treatment with insulin degludec resulted in a relative rate reduction (RRR) of 36% (95% confidence interval [CI]: 10%-54%; P < 0.05) in nocturnal CGM-recorded hypoglycemia (≤3.9 mmol/L), corresponding to an absolute rate reduction (ARR) of 0.85 events per person-week. In nocturnal CGM-recorded hypoglycemia (≤3.0 mmol/L), we found an RRR of 53% (95% CI: 36%-65%; P < 0.001), corresponding to an ARR of 0.75 events per person-week. At the lower detection limit of the CGM (≤2.2 mmol/L), treatment with insulin degludec resulted in a significant RRR of 58% (95% CI: 23%-77%; P = 0.005). The reductions were primarily due to significant RRRs in asymptomatic hypoglycemia. Conclusion: In people with T1D, prone to nocturnal severe hypoglycemia, insulin degludec compared with insulin glargine U100 significantly reduces nocturnal CGM-recorded hypoglycemia. www.clinicaltrials.gov (#NCT02192450).