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Home All Specialties Chronic Disease

Risk of major adverse cardiovascular events is lowest with glucagon-like-peptide-1 receptor agonists among patients with type 2 diabetes being treated with antihyperglycemics

bySimon Pan
January 13, 2026
in Chronic Disease, Endocrinology, Pharma
Reading Time: 2 mins read
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1. In patients with type 2 diabetes (T2D), the risk of major adverse cardiovascular events (MACEs) was lowest among patients undergoing sustained treatment with glucagon-like-peptide-1 receptor agonists (GLP-1RAs), followed by sodium-glucose cotransporter-2 inhibitors (SGLT2is), sulfonylureas and dipeptidyl peptidase-4 inhibitors (DPP4is).

Evidence Rating Level: 2 (Good)

MACEs remain the leading cause of mortality in patients with T2D. Previous studies have shown that GLP-1RAs and SGLT2is significantly reduce the incidence of MACEs in adults living with T2D, yet few studies have compared the protective effects of the various antihyperglycemic agents used in the management of T2D in preventing MACEs. This retrospective cohort study therefore sought to compare the risk of MACEs in adults with T2D receiving four different antihyperglycemic agents for T2D. 241,981 adults (mean [SD] age, 57.2 [12.9] years; 54.3% male) with T2D from 6 health care delivery systems across the United States were included in this study. Patients in this study were separated into groups based on medication classes (GLP-1RAs, SGLT2is, sulfonylureas and DPP4is). When comparing the cumulative incidence across the four groups, the adjusted 2.5 year average risk difference (ARD) showed a decrease in MACE risk over time with GLP-1RAs compared with SGLT2is (ARD, −0.006 [95% CI, −0.008 to −0.004]; P < .001), sulfonylureas (ARD, −0.013 [95% CI, −0.015 to −0.012]; P < .001), and DPP4is (ARD, −0.015 [95% CI, −0.018 to −0.011]; P < .001). Similarly, there was a decrease in MACE risk over time with SGLT2is compared with sulfonylureas (ARD, −0.007 [95% CI, −0.009 to −0.005]; P < .001) and DPP4is (ARD, −0.009 [95% CI, −0.013 to −0.005]; P < .001). Lastly, there was a decrease in MACE risk over time with sulfonylureas compared with DPP4is (ARD, −0.001 [95% CI, −0.005 to 0.002]; P = .47). Overall, this study found that among adult patients with T2D in the United States, GLP-1RAs offered the greatest protective effect against MACEs, followed by SGLT2is, sulfonylureas and DPP4is.

Click here to read this study in JAMA Network Open

Image: PD

©2025 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc. 

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Tags: dpp4iGLP1RAmajor adverse cardiovascular events (MACE)SGLT2 inhibitorsulfonylureaType 2 Diabetes Mellitus
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