REDUCED RISK OF HYPOGLYCEMIA WITH INSULIN DEGLUDEC VERSUS INSULIN GLARGINE IN PATIENTS WITH TYPE 2 DIABETES REQUIRING HIGH DOSES OF BASAL INSULIN: A META-ANALYSIS OF 5 RANDOMIZED BEGIN TRIALS

Objective: This meta-analysis of 5 trials from the Phase 3a insulin degludec (IDeg) clinical trial program evaluated the risk of hypoglycemia in a subset of subjects with type 2 diabetes (T2D) who required high basal insulin doses at the end of the trials. Methods: This meta-analysis compared glycated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), basal insulin dose, body weight, and rates of overall and nocturnal confirmed hypoglycemia in a pooled population of T2D subjects using >60 U basal insulin at trial completion. Five Phase 3a, open-label, randomized, treat-to-target, confirmatory 26-or 52-week trials with IDeg (n = 2,262) versus insulin glargine (IGlar) (n = 1,110) administered once daily were included. Overall confirmed hypoglycemia was defined as self-measured blood glucose <56 mg/dL or any episode requiring assistance; nocturnal confirmed hypoglycemia had an onset between 00: 01 and 05: 59 am. Results: More than one-third of IDeg-(35%) and IGlar-(34%) treated T2D subjects required > 60 U of basal insulin daily at the ends of the trial. Patients achieved similar mean HbA(1c) values (estimated treatment difference [ETD] IDeg -IGlar: 0.05%, P = .44) while mean FPG values were lower with IDeg than IGlar (ETD: -5.9 mg/ dL, P = .04) at end-of-trial. There was a 21% lower rate of overall confirmed hypoglycemic episodes for IDeg (estimated rate ratio [RR] IDeg/IGlar: 0.79, P = .02) and a 52% lower rate of nocturnal confirmed hypoglycemic episodes for IDeg (RR: 0.48, P<.01). Conclusion: In this post hoc meta-analysis, more than 30% of subjects with T2D required >60 U/day of basal insulin at the end of the trials. In these individuals, IDeg achieves similar HbA(1c) reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar.