title: Individualised treatment targets for elderly patients with type 2 diabetes using vildagliptin add-on or lone therapy (INTERVAL): a 24 week, randomised, double-blind, placebo-controlled study.
abstract: BACKGROUND
  Guidelines suggest setting individualised targets for glycaemic control in elderly patients with type 2 diabetes, despite no evidence. We aimed to assess the feasibility of setting and achieving individualised targets over 24 weeks along with conventional HbA1c reduction using vildagliptin versus placebo.
  
  
  METHODS
  In this multinational, double-blind, 24 week study, we enrolled drug-naive or inadequately controlled (glycosylated haemoglobin A1c [HbA1c] ≥7·0% to ≤10·0%) patients with type 2 diabetes aged 70 years or older from 45 outpatient centres in Europe. Investigators set individualised treatment targets on the basis of age, baseline HbA1c, comorbidities, and frailty status before a validated automated system randomly assigned patients (1:1) to vildagliptin (50 mg once or twice daily as per label) or placebo. Coprimary efficacy endpoints were proportion of patients reaching their investigator-defined HbA1c target and HbA1c reduction from baseline to study end. The study is registered with ClinicalTrials.gov, number NCT01257451, and European Union Drug Regulating Authorities Clinical Trials database, number 2010-022658-18.
  
  
  RESULTS
  Between Dec 22, 2010, and March 14, 2012, we randomly assigned 139 patients each to the vildagliptin and placebo groups. 37 (27%) of 137 patients in the placebo group achieved their individualised targets by education and interactions with the study team alone and 72 (52·6%) of 137 patients achieved their target in the vildagliptin group (adjusted odds ratio 3·16, 96·2% CI 1·81-5·52; p<0·0001). This finding was accompanied by a clinically relevant 0·9% reduction in HbA1c from a baseline of 7·9% with vildagliptin and a between-group difference of -0·6% (98·8% CI -0·81 to -0·33; p<0·0001). The overall safety and tolerability was similar in the vildagliptin and placebo groups, with low incidence of hypoglycaemia and no emergence of new safety signals.
  
  
  CONCLUSIONS
  This study is the first to introduce and show the feasibility of using individualised HbA1c targets as an endpoint in any type 2 diabetes population. Individualised glycaemic target levels are achievable with vildagliptin without any tolerability issues in the elderly type 2 diabetes population.
  
  
  BACKGROUND
  Novartis Pharma AG.
authors.affiliation: Diabetes and Vascular Research Centre, University of Exeter Medical School, Exeter, UK. Electronic address: d.strain@exeter.ac.uk.
authors.forename: W David
authors.initials: WD
authors.lastname: Strain
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Lukashevich
authors.affiliation: Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kothny
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Hoellinger
authors.affiliation: Novartis Pharma AG, Basel, Switzerland.
authors.forename: Päivi Maria
authors.initials: PM
authors.lastname: Paldánius
mesh_terms: D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005240:Feasibility Studies; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008687:Metformin / Q000008:administration & dosage; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects; D057285:Precision Medicine; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects; D013453:Sulfonylurea Compounds / Q000008:administration & dosage; D016896:Treatment Outcome; D000077597:Vildagliptin
chemical_list: D000218:Adamantane; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011759:Pyrrolidines; D013453:Sulfonylurea Compounds; D000077597:Vildagliptin