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 (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).


CONCLUSIONS
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.
Endocrine and Metabolic Consultants, Rockville, Maryland.
Helena W
HW
Rodbard
Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford and Oxford University Hospitals NHS Trust, Oxford, United Kingdom.
Stephen
S
Gough
Mountain Diabetes and Endocrine Center, Asheville, North Carolina.
Wendy
W
Lane
Novo Nordisk A/S, Søborg, Denmark.
Lars
L
Korsholm
Novo Nordisk A/S, Søborg, Denmark.
Ditte-Marie
DM
Bretler
Metabolic Institute of America, Tarzana, California.
Yehuda
Y
Handelsman
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D000069036:Insulin Glargine / Q000009:adverse effects / Q000627:therapeutic use*; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec