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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
Author(s) -
Del Prato S.,
Foley J. E.,
Kothny W.,
Kozlovski P.,
Stumvoll M.,
Paldánius P. M.,
Matthews D. R.
Publication year - 2014
Publication title -
diabetic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.474
H-Index - 145
eISSN - 1464-5491
pISSN - 0742-3071
DOI - 10.1111/dme.12508
Subject(s) - medicine , metformin , vildagliptin , regimen , randomized controlled trial , double blind , standard of care , diabetes mellitus , pharmacology , endocrinology , alternative medicine , placebo , pathology
Aims Durability of good glycaemic control (HbA 1c ) 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 HbA 1c . 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 HbA 1c 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. Summary 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.