title: Cardiovascular outcome trials for anti-diabetes medication: A holy grail of drug development?
abstract: Since the time questions arose on cardiovascular safety of Rosiglitazone, FDA has suggested guidelines on conduct of studies on anti-diabetic drugs so as to prove that the cardiovascular risk is acceptable. Based on the cardiovascular risks of pre-approval clinical trials, guidelines have been made to conduct cardiovascular safety outcome trials (CVSOTs) prior to the drug approval or after the drug has been approved. Unlike the trials comparing the efficacy of antidiabetic agents, the CVSOTs examine the cardiovascular safety of a drug in comparison to standard of care. These trials are expensive aspects of drug development and are associated with various technical and operational challenges. More cost effective models of assessing cardiovascular safety like use of biomarkers, electronic medical records, pragmatic and factorial designs can be adopted. This article critically looks at the antidiabetic drug approval from a cardiovascular perspective by asking a few questions and arriving at answers.
authors.affiliation: Consultant Endocrinologist, Department of Endocrinology and Diabetes, Providence Endocrine and Diabetes Specialty Centre, TC 1/2138, Murinjapalam, Trivandrum 695011, India. Electronic address: drmathewjohn@yahoo.com.
authors.forename: Mathew
authors.initials: M
authors.lastname: John
authors.affiliation: Chief Executive Officer and Endocrinologist, Chellaram Diabetes Institute, Pune, Maharashtra, India. Electronic address: unnikrishnanag@gmail.com.
authors.forename: Ambika
authors.initials: A
authors.lastname: Gopalakrishnan Unnikrishnan
authors.affiliation: Endocrinologist, Bharti Hospital and B.R.I.D.E., Karnal, Haryana 132001, India. Electronic address: brideknl@gmail.com.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kalra
authors.affiliation: Head, Department of Cardiology, PRS Hospital, Trivandrum, Kerala 695012, India. Electronic address: tinynair@gmail.com.
authors.forename: Tiny
authors.initials: T
authors.lastname: Nair
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002423:Cause of Death / Q000639:trends; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D017277:Drug Approval; D014943:Global Health; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015994:Incidence; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents
keywords: Anti diabetic drugs; Cardiovascular; Trials