Clinical Trial for Antidiabetic Drugs: FDA Guidance for Diabetes Mellitus-Evaluation of Cardiovascular Risk in New Antidiabetic Therapies.

Nam,  Moonsuk

doi:2011.12.3.129

J Korean Diabetes > Volume 12(3); 2011 > Article

Opinion

The Journal of Korean Diabetes 2011;12(3):129-132.
DOI: https://doi.org/10.4093/kcd.2011.12.3.129 Published online September 1, 2011.

당뇨병약제 임상시험: 당뇨병신약의 심혈관 위험도평가 FDA Guidance

남문석

Clinical Trial for Antidiabetic Drugs: FDA Guidance for Diabetes Mellitus-Evaluation of Cardiovascular Risk in New Antidiabetic Therapies.

Moonsuk Nam

Department of Internal Medicine/Clinical Trial Center, Inha University College of Medicine, Incheon, Korea. namms@inha.ac.kr

Abstract

Type 2 diabetes is rapidly increasing worldwide, and there have been many advances in the care of diabetic patients. Nevertheless, less than half of the patients are achieving the glycemic goal of HbA1c < 7%. This shows that current therapeutic modalities have limitations, and the need for continued development of new antidiabetic drugs is clear. In 2007, a meta-analysis focusing on the thiazolidinedione drug rosiglitazone suggested an unacceptably high cardiovascular risk for this newly approved drug, prompting changes in regulations for antidiabetic drug development. The FDA guidance for Diabetes Mellitus-Evaluation of Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes was released as a draft in Feb 2008, and the final form was published in December 2008. The guidance, though not a regulation, requires developers to demonstrate that all new antidiabetic agents have an acceptable cardiovascular risk. The European Medicine Agency (EMA) also published a draft guideline in January 2010 on the clinical investigation of medicinal products for the treatment of diabetes mellitus which included a cardiovascular safety assessment component. Considering the increased CV risk in type 2 diabetic patients, antidiabetic drugs should not result in an unacceptable increase in cardiovascular risk. The FDA has offered guidelines for the assessment of cardiovascular safety for antidiabetic drugs. Careful prospective planning of clinical trials (choice of study type, subject selection, and meta-analysis) and thorough preclinical safety assessment (choice of cardiovascular endpoints: MACE, endpoint adjudication) are needed to assess possible cardiovascular risk.

Key Words: Food and Drug Administration guidance, Antidiabetic drugs, Cardiovascular risk, Good clinical practice