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World J Diabetes. Jun 15, 2019; 10(6): 324-332
Published online Jun 15, 2019. doi: 10.4239/wjd.v10.i6.324
Prevention of macrovascular complications in patients with type 2 diabetes mellitus: Review of cardiovascular safety and efficacy of newer diabetes medications
Ravi Kant, Kashif M Munir, Arshpreet Kaur, Vipin Verma
Ravi Kant, Division of Endocrinology, Diabetes and Nutrition, Medical University of South Carolina/Anmed Campus, Anderson, SC 29621, United States
Kashif M Munir, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, United States
Arshpreet Kaur, Division of Endocrinology, Diabetes and Nutrition, Sinai Hospital, Baltimore, MD 21215, United States
Vipin Verma, Department of Medicine, Medical University of South Carolina/Anmed Campus, Anderson, SC 29621, United States
Author contributions: Kant R performed the majority of the writing, prepared the tables; Verma V designed the outline and performed the writing; Munir KM and Kaur A provided the input in writing the paper and edited the paper.
Conflict-of-interest statement: There is no conflict of interest associated with any of the senior author or other coauthors contributed their efforts in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ravi Kant, MD, Affiliate Associate Professor, Division of Endocrinology, Diabetes and Nutrition, Medical University of South Carolina/Anmed Campus, 2000 E Greenville St., Suite # 3100, Anderson, SC 29621, United States. kant.ravi.md@gmail.com
Telephone: +1-864-5124160 Fax: +1-864-5124165
Received: February 21, 2019
Peer-review started: February 22, 2019
First decision: May 8, 2019
Revised: May 15, 2019
Accepted: May 23, 2019
Article in press: May 23, 2019
Published online: June 15, 2019
Processing time: 113 Days and 19.1 Hours
Abstract

Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.

Keywords: Newer antidiabetic medications; Glucagon-like peptide-1 receptor agonist; Sodium-glucose cotransporter-2 inhibitors; Type 2 diabetes mellitus; Macrovascular complications; Cardiovascular outcome trials; Major cardiovascular events; Heart failure; Prevention of heart disease

Core tip: Multiple cardiovascular (CV) outcome trials performed mainly to meet regulatory requirements by United States Food and Drug Administration have provided very important findings on CV safety and efficacy of newer anti-diabetic drugs. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2)-inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.