title: Clinical trial risk in type-2 diabetes: importance of patient history.
abstract: OBJECTIVE
  To determine the risk of clinical trial failure for drugs developed for type-2 diabetes.
  
  
  METHODS
  Drugs were investigated by reviewing phase I to phase III studies that were conducted between 1998 and February 2013. The clinical trial success rates were calculated and compared to the industry standard. The drugs were classified into GLP-1 receptor agonists, DPP-4 inhibitors, SGLT-2 inhibitors and "Other". The exclusion criteria for drugs in this study: Drugs that were started in phase I studies prior to January 1998 for this indication and drugs whose primary indications were not for the control of blood glucose levels.
  
  
  RESULTS
  Data was extracted from clinicaltrials.gov; there were a total of 131 drug candidates that fit our specified criteria, of which 8 received FDA approval. The cumulative success rate for molecules developed for type-2 diabetes is 10%. Small molecules were more successful than biologics. A strong disparity was observed in phase III, with studies that utilised treatment naïve patients having a 40% success rate, compared to an 83% success rate in patients who have had previous anti-hyperglycemic exposure.
  
  
  CONCLUSIONS
  1 in 10 drugs that enter clinical testing in this disease will be approved. The DPP-4 inhibitor class of drugs had the highest success rate of all drug classes with a 63% cumulative success rate; while treatment naïve patients carried the greatest clinical trial risk.
authors.affiliation: Department of Biology, University of Toronto at Mississauga, Toronto, ON.
authors.forename: Emmanuel O
authors.initials: EO
authors.lastname: Aiyere
authors.forename: Jay
authors.initials: J
authors.lastname: Silverberg
authors.forename: Safina
authors.initials: S
authors.lastname: Ali
authors.forename: Jayson L
authors.initials: JL
authors.lastname: Parker
mesh_terms: D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents