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

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 100883645 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1463-1326 (Electronic) Linking ISSN: 14628902 NLM ISO Abbreviation: Diabetes Obes Metab Subsets: MEDLINE

Original Publication: Oxford : Wiley-Blackwell, c1999-

Practice Guidelines as Topic* ; Practice Patterns, Physicians'*/standards ; Practice Patterns, Physicians'*/statistics & numerical data; Diabetes Mellitus, Type 2/*drug therapy ; Guideline Adherence/*statistics & numerical data ; Hypoglycemic Agents/*therapeutic use ; United States Food and Drug Administration/*standards; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/prevention & control ; Cardiovascular System/drug effects ; Diabetes Mellitus, Type 2/epidemiology ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Drug-Related Side Effects and Adverse Reactions/prevention & control ; Humans ; Patient Safety/standards ; Time Factors ; United States

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.
(© 2019 John Wiley & Sons Ltd.)

Comment in: Diabetes Obes Metab. 2019 May;21(5):1079-1080. (PMID: 30762280)

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

0 (Hypoglycemic Agents)

Date Created: 20190129 Date Completed: 20200330 Latest Revision: 20200330

20240628

10.1111/dom.13645

30690856