Effect of insulin analogues on frequency of non-severe hypoglycaemia in patients with type 1 diabetes prone to severe hypoglycaemia: The HypoAna trial

• Published in: Diabetes & metabolism 2016-09, Vol.42 (4), p.249-255
• Main Authors: Agesen, R.M, Kristensen, P.L, Beck-Nielsen, H, Nørgaard, K, Perrild, H, Christiansen, J.S, Jensen, T, Hougaard, P, Parving, H.H, Thorsteinsson, B, Tarnow, L, Pedersen-Bjergaard, U
• Format: Article
• Language: English
• Subjects: Adult; Aged; Blood Glucose - drug effects; Blood Glucose - metabolism; Cross-Over Studies; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - epidemiology; Disease Susceptibility; Endocrinology & Metabolism; Female; Humans; Hypoglycemia - chemically induced; Hypoglycemia - epidemiology; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Incidence; Insulin - administration & dosage; Insulin - adverse effects; Insulin - analogs & derivatives; Insulin analogues; Insulin Aspart - administration & dosage; Insulin Aspart - adverse effects; Insulin Detemir - administration & dosage; Insulin Detemir - adverse effects; Insulin, Isophane - administration & dosage; Insulin, Isophane - adverse effects; Internal Medicine; Male; Middle Aged; Nocturnal hypoglycaemia; Non-severe hypoglycaemia; Randomized controlled trial; Severity of Illness Index; The HypoAna trial; Type 1 diabetes
• ISSN: 1262-3636; 1878-1780
• DOI: 10.1016/j.diabet.2016.03.001

Abstract Aim Insulin analogues reduce the risk of hypoglycaemia compared with human insulin in patients with type 1 diabetes (T1D) and minor hypoglycaemia problems. The HypoAna trial showed that, in patients with recurrent severe hypoglycaemia, treatment based on insulin analogues reduces the risk of severe hypoglycaemia. The present study aims to assess whether this also applies to non-severe hypoglycaemia events during the day and at night. Methods This 2-year investigator-initiated multicentre, prospective, randomized, open, blinded endpoint (PROBE) trial involved patients with T1D and at least two episodes of severe hypoglycaemia during the previous year. Using a balanced crossover design, patients were randomized to basal–bolus therapy based on analogue (detemir/aspart) or human (NPH/regular) insulins. A total of 114 participants were included. Endpoints were the number of severe hypoglycaemic events and non-severe events, including documented symptomatic and asymptomatic episodes occurring during the day and at night (ClinicalTrials.gov number: NCT00346996 ). Results Analogue-based treatment resulted in a 6% (2–10%; P = 0.0025) overall relative risk reduction of non-severe hypoglycaemia. This was due to a 39% (32–46%; P < 0.0001) reduction of non-severe nocturnal hypoglycaemia, seen for both symptomatic (48% [36–57%]; P < 0.0001) and asymptomatic (28% [14–39%]; P = 0.0004) nocturnal hypoglycaemia episodes. No clinically significant differences in hypoglycaemia occurrence were observed between the insulin regimens during the day. The time needed to treat one patient with insulin analogues to avoid one episode (TNT1) of non-severe nocturnal hypoglycaemia was approximately 3 months. Conclusion In T1D patients prone to severe hypoglycaemia, treatment with analogue insulin reduced the risk of non-severe nocturnal hypoglycaemia compared with human insulin.