Effect of US Food and Drug Administration's Cardiovascular Safety Guidance on Diabetes Drug Development

Clin Pharmacol Ther. 2017 Aug;102(2):290-296. doi: 10.1002/cpt.705. Epub 2017 May 27.


In 2008, the US Food and Drug Administration (FDA) issued guidance on the need for cardiovascular outcome trials to assess the safety of new diabetes medications. Using two large commercial databases, we evaluated the effect of the FDA's cardiovascular safety guidance on drug development for type 2 diabetes as well as a comparison group of drugs intended to treat other alimentary and metabolic conditions. The FDA's guidance was associated with a 31% differential decrease in the rate of diabetes drugs entering phase II trials, but the remaining drugs were significantly more likely to target novel biological pathways (72% of drugs had novel mechanisms after the guidance vs. 49% before the guidance). No differential changes were observed for phase I and phase III trials. There was no measurable improvement during the study period in glycemic efficacy among investigational products entering phase III trials. This research highlights how regulatory actions can impact pharmaceutical innovation.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Clinical Trials as Topic / methods
  • Databases, Factual / trends
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Drugs, Investigational / adverse effects
  • Drugs, Investigational / therapeutic use*
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • United States / epidemiology
  • United States Food and Drug Administration / legislation & jurisprudence
  • United States Food and Drug Administration / standards*


  • Drugs, Investigational
  • Hypoglycemic Agents