Format

Send to

Choose Destination
Diabetes Obes Metab. 2019 May;21(5):1073-1078. doi: 10.1111/dom.13645. Epub 2019 Mar 12.

FDA guidance on antihyperglyacemic therapies for type 2 diabetes: One decade later.

Author information

1
Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, Texas.
2
Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Aachen, Germany.
3
Clinical Development, Therapeutic Area Cardiometabolism, Boehringer Ingelheim, Asker, Norway.
4
Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut.
5
Dallas Diabetes Research Center at Medical City and University of Texas, Southwestern Medical Center, Dallas, Texas.
6
Clinical Development, Therapeutic Area Cardiometabolism, Boehringer Ingelheim, Ingelheim, Germany.

Abstract

In 2008, the US Food and Drug Administration (FDA) issued a guidance to industry statement concerning evaluation of the cardiovascular (CV) safety of new antihyperglycaemic therapies for type 2 diabetes. Fifteen CV outcome trials assessing three novel classes of antihyperglycaemic therapies, DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors, were completed by the end of 2018 and several others are ongoing. In addition, one comparative insulin trial also has been completed. None of these trials reported an increase in risk for major adverse CV events (MACE), and six agents have demonstrated CV benefits. This experience has led to the first FDA-approved indications for antihyperglycaemic medications to reduce the risk of CV death (empagliflozin) and to reduce the risk of MACE (liraglutide, canagliflozin), both indications specific to patients with established atherosclerotic cardiovascular disease (ASCVD). Because of the aggregate results from dedicated CV outcomes trials conducted in response to the FDA guidance statement, the contemporary paradigm for treatment of patients with type 2 diabetes has evolved substantially. However, the guidance has substantially increased the cost of developing new medications to address this important disease that afflicts hundreds of millions of adults worldwide, with reduction in quality of life as well as in life expectancy. The cost burden of drug development of medications proven effective that may directly impact cost to patients and to their insurers might be alleviated by modifications to the present guidance statement. These include areas of trial design, aspects of trial operation, expansion of composite outcomes to include broader component CV outcomes and continued evolution of analytic methodology. The guidance statement will benefit from consideration of a number of modifications to support continued innovation and, of course, the safety of marketed medications for type 2 diabetes. However, the requirement to assess each new antihyperglycaemic medication in at least one large-scale standard randomized clinical outcomes trial should remain, so that clinicians can be reassured about the favourable efficacy/safety profiles of the medications they prescribe.

KEYWORDS:

GLP-1 receptor agonist; DPP-4 inhibitor; SGLT-2 inhibitor; Type 2 diabetes; cardiovascular outcomes; heart failure; regulatory

PMID:
30690856
DOI:
10.1111/dom.13645

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center