title: Study to determine the durability of glycaemic control with early treatment with a vildagliptin-metformin combination regimen vs. standard-of-care metformin monotherapy-the VERIFY trial: a randomized double-blind trial.
abstract: OBJECTIVE
  Durability of good glycaemic control (HbA1c ) is of importance as it can be the foundation for delaying diabetic complications. It has been hypothesized that early initiation of treatment with the combination of oral anti-diabetes agents with complementary mechanisms of action can increase the durability of glycaemic control compared with metformin monotherapy followed by a stepwise addition of oral agents. Dipeptidyl peptidase-4 inhibitors are good candidates for early use as they are efficacious in combination with metformin, show weight neutrality and a low risk of hypoglycaemia. We aimed to test the hypothesis that early combined treatment of metformin and vildagliptin slows β-cell deterioration as measured by HbA1c .
  
  
  METHODS
  Approximately 2000 people with Type 2 diabetes mellitus who were drug-naive or who were treated with metformin for less than 1 month, and who have HbA1c of 48-58 mmol/mol (6.5-7.5%), will be randomized in a 1:1 ratio in VERIFY, a 5-year multinational, double-blind, parallel-group study designed to compare early initiation of a vildagliptin-metformin combination with standard-of-care initiation of metformin monotherapy, followed by the stepwise addition of vildagliptin when glycaemia deteriorates. Further deterioration will be treated with insulin. The primary analysis for treatment failure will be from a Cox proportional hazard regression model and the durability of glycaemic control will be evaluated by assessing treatment failure rate and the rate of loss in glycaemic control over time as co-primary endpoints.
  
  
  CONCLUSIONS
  VERIFY is the first study to investigate the long-term clinical benefits of early combination treatment vs. the standard-of-care metformin monotherapy with a second agent added by threshold criteria.
authors.affiliation: Department of Endocrinology and Metabolism, Section of Metabolic Diseases and Diabetes, University of Pisa, Pisa, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Del Prato
authors.forename: J E
authors.initials: JE
authors.lastname: Foley
authors.forename: W
authors.initials: W
authors.lastname: Kothny
authors.forename: P
authors.initials: P
authors.lastname: Kozlovski
authors.forename: M
authors.initials: M
authors.lastname: Stumvoll
authors.forename: P M
authors.initials: PM
authors.lastname: Paldánius
authors.forename: D R
authors.initials: DR
authors.lastname: Matthews
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications; D050177:Overweight / Q000150:complications; D011759:Pyrrolidines / Q000627:therapeutic use*; D012107:Research Design; D000077597:Vildagliptin; D055815:Young Adult
chemical_list: D000218:Adamantane; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D009570:Nitriles; D011759:Pyrrolidines; D000077597:Vildagliptin; C517652:hemoglobin A1c protein, human