DIRECT - Innovative Medicines Initiative:
DIabetes REsearCh on patient straTification

Work Package 7 (WP7):
Validation of biomarkers for drug response
in small clinical trials

The aim of the clinical trial work packages 7&8 will be primarily to validate biomarkers from discovery work packages 2 to 5 as predictors of events in prospective clinical trials. Additionally it may be possible to establish their clinical utility as predictive or response (surrogate) biomarkers for shortening clinical trials.

The clinical trial design will clearly depend upon the biomarkers discovered in part 1 of the project, but will range from several smaller trials to validate biomarkers of therapeutic response to a large trial of an intervention to delay progression of diabetes or pre-diabetes (WP8).

The WP7 trials are of short duration and will follow on from the outputs of work package 3 (biomarkers predicting response/non-response to metformin, sulphonylureas, GLP-1 receptor agonists, metformin intolerance and non-remission with obesity surgery). The decision of final study design will depend on the biomarkers available at year four, when we expect to have a range of markers (genomic, proteomic, metabolomic, lipidomic, physiological and imaging) that predict variation in response or intolerance to diabetes drugs including metformin, sulphonylureas, or GLP-1 receptor analogues, or predict remission from diabetes following obesity surgery.

In WP7 simple 6-month intervention studies will be carried out in 200-300 type 2 diabetes patients, each, based upon a simple study design of the four phenotypes investigated in WP3.

Possible WP7 clinical trials are:

  • Response / non-response or intolerance to metformin
  • Sulphonylurea response / non-response
  • GLP-1 receptor agonist response / non-response

  • Sanofi-Aventis Deutschland GmbH
  • University of Dundee
  • University of Bath
  • Helmholtz Zentrum München – Deutsches Forschungszentrum für Gesundheit und Umwelt GmbH
  • Imperial College London
  • University of Lille - CNRS
  • Eli Lilly and Company Ltd.