title: Improved glucose control with reduced hypoglycaemic risk when linagliptin is added to basal insulin in elderly patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess the efficacy, hypoglycaemia risk and other safety markers of linagliptin as an additional therapy in older patients (aged ≥70 years) inadequately controlled with basal insulin.
  
  
  METHODS
  A prespecified safety analysis from the linagliptin trials programme was carried out to explore the hypoglycaemia risk when linagliptin was added to background basal insulin therapy in elderly patients (≥70 years). To do this, two eligible, randomized, placebo-controlled, clinical trials (NCT00954447 and NCT01084005) of 24 and ≥52 weeks, respectively, were analysed.
  
  
  RESULTS
  A total of 247 elderly individuals [mean ± standard deviation (s.d.) age 74 ± 4 years, glycated haemoglobin (HbA1c) 8.2 ± 0.8%] on basal insulin (mean ± s.d. baseline dose 36 ± 25 IU/day) were identified. Alongside placebo-adjusted change in HbA1c with linagliptin of -0.77% [95% confidence interval (CI) -0.95 to 0.59; p < 0.0001] after 24 weeks, the hazard ratios (HRs) of both overall and confirmed hypoglycaemia [blood glucose ≤3.9 mmol/l (70 mg/dl)], were significantly lower with linagliptin than with placebo: HR 0.61 (95% CI 0.39-0.97) versus 0.59 (95% CI 0.37-0.94), respectively (both p < 0.05). Moreover, significantly less confirmed hypoglycaemia was present in linagliptin-treated patients with renal impairment [HR 0.45 (95% CI 0.27-0.76)], moderate hyperglycaemia [HbA1c 7.5 to <9.0%; HR 0.51 (95% CI 0.27-0.99)], lower fasting plasma glucose levels [<152 mg/dl; HR 0.49 (95% CI 0.28-0.86)] and those treated with higher insulin doses [insulin ≥35.6 IU/day; HR 0.46 (95% CI 0.23-0.91); p < 0.05 for all]. Severe hypoglycaemia was rare and the incidence was lower with linagliptin (0.8%) versus placebo (2.5%): HR 0.21 (95% CI 0.02-2.30).
  
  
  CONCLUSIONS
  Despite improvements in hyperglycaemia and no relevant on-trial insulin dose reductions, adding linagliptin to basal insulin appears to decrease hypoglycaemia risk. The biological basis of this phenomenon warrants further research but may involve counter-regulatory effects of incretin hormones.
authors.affiliation: Yale-New Haven Hospital, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Inzucchi
authors.affiliation: Division of Diabetology, St. Josef Hospital, Ruhr-University Bochum, Bochum, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: Nauck
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Hehnke
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Woerle
authors.affiliation: Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Eynatten
authors.affiliation: Center for Metabolic Research, Veterans Affairs San Diego Healthcare System, University of California San Diego School of Medicine, San Diego, CA, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Henry
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004359:Drug Therapy, Combination / Q000379:methods; D005215:Fasting / Q000097:blood; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology; D015994:Incidence; D049528:Insulin, Long-Acting / Q000008:administration & dosage*; D000069476:Linagliptin / Q000008:administration & dosage*; D008297:Male; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D049528:Insulin, Long-Acting; D000069476:Linagliptin; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; hypoglycaemia; linagliptin; type 2 diabetes mellitus