title: Efficacy and tolerability of saxagliptin compared with glimepiride in elderly patients with type 2 diabetes: a randomized, controlled study (GENERATION).
abstract: OBJECTIVE
  To assess the efficacy and safety of adjunctive saxagliptin vs glimepiride in elderly patients with type 2 diabetes (T2D) and inadequate glycaemic control.
  
  
  METHODS
  In this multinational, randomized, double-blind, phase IIIb/IV study (GENERATION; NCT01006603), patients aged ≥65 years were randomized (1 : 1) to receive saxagliptin 5 mg/day or glimepiride ≤6 mg/day, added to metformin, during a 52-week treatment period. The primary endpoint was achievement of glycated haemoglobin (HbA1c) <7.0% at week 52 without confirmed/severe hypoglycaemia. The key secondary endpoint was incidence of confirmed/severe hypoglycaemia. Safety and tolerability were also assessed.
  
  
  RESULTS
  Of 720 patients randomized (360 in each treatment group; mean age 72.6 years; mean T2D duration 7.6 years), 574 (79.8%) completed the study (saxagliptin 80.3%; glimepiride 79.2%). Similar proportions of patients achieved the primary endpoint with saxagliptin and glimepiride (37.9 vs 38.2%; odds ratio 0.99, 95% confidence interval 0.73, 1.34; p = 0.9415); however, a significant treatment-by-age interaction effect was detected (p = 0.0389): saxagliptin was numerically (but not significantly) superior to glimepiride for patients aged <75 years (39.2 vs 33.3%) and numerically inferior for patients aged ≥75 years (35.9 vs 45.5%). The incidence of confirmed/severe hypoglycaemia was lower with saxagliptin vs glimepiride (1.1 vs 15.3%; nominal p < 0.0001). Saxagliptin was generally well tolerated, with similar incidences of adverse events compared with glimepiride.
  
  
  CONCLUSIONS
  As avoiding hypoglycaemia is a key clinical objective in elderly patients, saxagliptin is a suitable alternative to glimepiride in patients with T2D aged ≥65 years.
authors.affiliation: Department of Medicine I, Rudolfstiftung Hospital, Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Schernthaner
authors.affiliation: Unidad de Gestion de Endocrinología y Nutrición, Hospital Universitario de Valme, Sevilla, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Durán-Garcia
authors.affiliation: Study centre Professor Hanefeld, GWT-TUD GmbH, Dresden, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Hanefeld
authors.affiliation: Lipid Clinic, Oslo University Hospital, Oslo, Norway.
authors.forename: G
authors.initials: G
authors.lastname: Langslet
authors.affiliation: Endocrinology and Metabolism, Abdominal Center, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
authors.forename: L
authors.initials: L
authors.lastname: Niskanen
authors.affiliation: Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
authors.forename: C J
authors.initials: CJ
authors.lastname: Östgren
authors.affiliation: AstraZeneca, Istanbul, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Malvolti
authors.affiliation: AstraZeneca LP, Wilmington, DE, USA.
authors.forename: E
authors.initials: E
authors.lastname: Hardy
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004151:Dipeptides / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000218:Adamantane; D001786:Blood Glucose; D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride; C502994:saxagliptin
keywords: dipeptidyl peptidase-4 inhibitor; randomized trial; sulphonylureas; type 2 diabetes