title: Regardless of the degree of glycaemic control, linagliptin has lower hypoglycaemia risk than all doses of glimepiride, at all time points, over the course of a 2-year trial.
abstract: OBJECTIVE
  To evaluate the risk of documented hypoglycaemia with glimepiride versus linagliptin.
  
  
  METHODS
  This was an exploratory analysis of data from a 2-year, randomized, double-blind study of the dipeptidyl peptidase-4 inhibitor linagliptin 5 mg once daily (n = 764) versus the sulphonylurea glimepiride 1-4 mg once daily (n = 755) in patients with type 2 diabetes uncontrolled by metformin. Patients randomized to glimepiride started on 1 mg and after 4 weeks were allowed to be individually uptitrated stepwise to glimepiride 4 mg if a fasting plasma glucose concentration ≤6.1 mmol/l was not achieved. Investigator-reported hypoglycaemia was evaluated by dose, over time, and by the degree of glycated haemoglobin (HbA1c) reduction.
  
  
  RESULTS
  The percentages of patients with at least one hypoglycaemic event at the individual maximum glimepiride dose were: 1 mg, 45.0%; 2 mg, 50.8%; 3 mg, 36.1%; and 4 mg, 27.7%. The incidence of hypoglycaemia was higher with glimepiride than with linagliptin (36.1 vs. 7.5%; p < 0.0001); after performing sensitivity analyses by excluding events during dose escalation (weeks 0-16), this difference remained significant (weeks 16-104: 25.8 vs. 5.9%; p < 0.0001). Notably, the incidence of hypoglycaemia was higher with glimepiride than with linagliptin in each quartile of HbA1c change from baseline (all p < 0.0001); the incidence of hypoglycaemic episodes was not increased with greater reductions in HbA1c in either group. In all 4-week intervals across the 2-year study, the incidence of hypoglycaemia was lower with linagliptin than with glimepiride.
  
  
  CONCLUSIONS
  Linagliptin was associated with a lower risk of hypoglycaemia than glimepiride at all dose levels and time intervals, and regardless of change in HbA1c level.
authors.affiliation: Department of Medicine IV, Universitätsklinikum Tübingen, Tübingen, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Gallwitz
authors.forename: J
authors.initials: J
authors.lastname: Rosenstock
authors.forename: S
authors.initials: S
authors.lastname: Patel
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
authors.forename: U
authors.initials: U
authors.lastname: Hehnke
authors.forename: L
authors.initials: L
authors.lastname: Mehlburger
authors.forename: K A
authors.initials: KA
authors.lastname: Dugi
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced*; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000069476:Linagliptin; D008297:Male; D008875:Middle Aged; D011687:Purines / Q000008:administration & dosage / Q000009:adverse effects*; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects*; D012306:Risk; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000069476:Linagliptin; D011687:Purines; D011799:Quinazolines; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride
keywords: DPP-4 inhibitor; glycaemic control; incretin therapy; sulphonylurea; type 2 diabetes