From Clinical Trial Evidence to Clinical Guidelines: Perspectives on REWIND from Clinicians in the Gulf and Levant Region

Background: Current guidelines recommend that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with proven cardiovascular benefit should be considered for first-line therapy in patients with type 2 diabetes (T2D) who have/are at high risk of atherosclerotic cardiovascular disease (CVD). Summary: Only one GLP-1 RA – dulaglutide – has demonstrated superiority versus placebo in reducing cardiovascular risk in patients with T2D with or without a history of CVD in a cardiovascular outcomes trial (CVOT). This trial – REWIND – is the only GLP-1 RA-based CVOT that recruited patients with a CVD prevalence (31%) that is similar to the estimated prevalence in primary care T2D populations in the Gulf and Levant region. In contrast, baseline CVD prevalence in all other GLP-1 RA-based CVOTs ranged from 73 to 100%. REWIND’s results provided the European Association for the Study of Diabetes and American Diabetes Association with data on which to base updated guidelines. These organisations subsequently recommended that GLP-1 RAs should be considered for primary CVD prevention in high cardiovascular-risk patients with T2D, and acknowledged that present evidence supporting GLP-1 RAs for primary prevention of CVD in T2D is strongest for dulaglutide but limited for other GLP-1 RAs. The Emirates Diabetes Society guidelines also support the use of GLP-1 RAs for primary cardiovascular prevention in patients with T2D. The cardiovascular benefit conferred by dulaglutide in patients with no CVD history, and the close alignment of the REWIND cohort with patient populations in the Gulf and Levant region, may better inform physicians in the early use of dulaglutide in patients with T2D and multiple cardiovascular-risk factors, regardless of CVD history. Utilizing published data and author opinion, this review explores the importance of taking a cardiocentric approach to T2D management, and discusses the clinical implications of REWIND for people with T2D in the Gulf and Levant region. Key Messages: Guideline recommendations, including those of the Emirates Diabetes Society, state that GLP-1 RAs with proven cardiovascular benefit should be considered for primary CVD prevention in high cardiovascular-risk patients with T2D. This recommendation was informed, in part, by REWIND; REWIND was the only CVOT to show that a GLP-1 RA (dulaglutide) reduces cardiovascular risk in patients with T2D with or without established CVD. Demonstration of cardiovascular benefit in the REWIND cohort, which aligns closely with patient populations in the Gulf and Levant region, may better inform physicians in the early use of dulaglutide in patients with T2D, regardless of CVD history.