Helena W Rodbard1, Stephen Gough2, Wendy Lane3, Lars Korsholm4, Ditte-Marie Bretler4, Yehuda Handelsman5. 1. Endocrine and Metabolic Consultants, Rockville, Maryland. 2. Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, United Kingdom. 3. Mountain Diabetes and Endocrine Center, Asheville, North Carolina. 4. Novo Nordisk A/S, Søborg, Denmark. 5. Metabolic Institute of America, Tarzana, California.
Abstract
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 (HbA1c), 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 HbA1c 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 HbA1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar.
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 (HbA1c), 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 HbA1c 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 HbA1c reduction with significantly less overall and nocturnal confirmed hypoglycemia compared with IGlar.