title: Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials.
abstract: OBJECTIVE
  Hypoglycaemia and the fear of hypoglycaemia are barriers to achieving normoglycaemia with insulin. Insulin degludec (IDeg) has an ultra-long and stable glucose-lowering effect, with low day-to-day variability. This pre-planned meta-analysis aimed to demonstrate the superiority of IDeg over insulin glargine (IGlar) in terms of fewer hypoglycaemic episodes at equivalent HbA1c in type 2 and type 1 diabetes mellitus (T2DM/T1DM).
  
  
  METHODS
  Pooled patient-level data for self-reported hypoglycaemia from all seven (five in T2DM and two in T1DM) randomized, controlled, phase 3a, treat-to-target trials in the IDeg clinical development programme comparing IDeg once-daily (OD) vs. IGlar OD were analysed.
  
  
  RESULTS
  Four thousand three hundred and thirty subjects (2899 IDeg OD vs. 1431 IGlar OD) were analysed. Among insulin-naïve T2DM subjects, significantly lower rates of overall confirmed, nocturnal confirmed and severe hypoglycaemic episodes were reported with IDeg vs. IGlar: estimated rate ratio (RR):0.83[0.70;0.98](95%)             (CI) , RR:0.64[0.48;0.86](95%)             (CI)  and RR:0.14[0.03;0.70](95%)             (CI) . In the overall T2DM population, significantly lower rates of overall confirmed and nocturnal confirmed episodes were reported with IDeg vs. IGlar [RR:0.83[0.74;0.94](95%)             (CI)  and RR:0.68[0.57;0.82](95%)             (CI) ). In the T1DM population, the rate of nocturnal confirmed episodes was significantly lower with IDeg vs. IGlar during maintenance treatment (RR:0.75[0.60;0.94](95%)             (CI) ). Reduction in hypoglycaemia with IDeg vs. IGlar was more pronounced during maintenance treatment in all populations.
  
  
  CONCLUSIONS
  The limitations of this study include the open-label design and exclusion of subjects with recurrent severe hypoglycaemia. This meta-analysis confirms that similar improvements in HbA1c can be achieved with fewer hypoglycaemic episodes, particularly nocturnal episodes, with IDeg vs. IGlar across a broad spectrum of patients with diabetes.
authors.affiliation: Division of Endocrinology, Department of Medicine, Georgetown University School of Medicine, Washington, DC, USA. rratner@diabetes.org
authors.forename: R E
authors.initials: RE
authors.lastname: Ratner
authors.forename: S C L
authors.initials: SC
authors.lastname: Gough
authors.forename: C
authors.initials: C
authors.lastname: Mathieu
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.forename: B
authors.initials: B
authors.lastname: Bode
authors.forename: H
authors.initials: H
authors.lastname: Mersebach
authors.forename: L
authors.initials: L
authors.lastname: Endahl
authors.forename: B
authors.initials: B
authors.lastname: Zinman
mesh_terms: D017326:Clinical Trials, Phase III as Topic; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; C517652:hemoglobin A1c protein, human; C571886:insulin degludec