Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): A phase 3, randomised, open-label, treat-to-target non-inferiority trial

摘要

Background Basal insulin therapy does not stop loss of ?-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess effi cacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged =18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA1c) of 7.0-10.0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratifi ed by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3.9-<5.0 mmol/L self-measured before breakfast. The primary outcome was non-inferiority of degludec to glargine measured by change in HbA1c from baseline to week 52 (non-inferiority limit of 0.4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58.9 years [SD 9.3], diabetes duration 13.5 years [7.3], HbA1c 8.3% [0.8], and fasting plasma glucose 9.2 mmol/L [3.1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA1c decreased by 1.1% in the degludec group and 1.2% in the glargine group (estimated treatment diff erence [degludec-glargine] 0.08%, 95% CI-0.05 to 0.21), confi rming non-inferiority. Rates of overall confi rmed hypoglycaemia (plasma glucose <3.1 mmol/L or severe episodes requiring assistance) were lower with degludec than glargine (11.1 vs 13.6 episodes per patient-year of exposure; estimated rate ratio 0.82, 95% CI 0.69 to 0.99; p=0.0359), as were rates of nocturnal confi rmed hypoglycaemia (1.4 vs 1.8 episodes per patient-year of exposure; 0.75, 0.58 to 0.99; p=0.0399). Rates of severe hypoglycaemia seemed similar (0.06 vs 0.05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of diff erences. Rates of other adverse events did not diff er between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine.