Effectiveness of glucose-lowering medications on cardiovascular outcomes in patients with type 2 diabetes at moderate cardiovascular risk
Open accessAbstract
Cardiovascular disease (CVD) is the leading cause of death among people with type 2 diabetes 1-5, most of whom are at moderate CVD risk 6, yet there is limited evidence on the preferred choice of glucose-lowering medication for CVD risk reduction in this population. Here, we report the results of a retrospective cohort study where data for US adults with type 2 diabetes and moderate risk for CVD are used to compare the risks of experiencing a major adverse cardiovascular event with initiation of glucagon-like peptide-1 receptor agonists (GLP-1RA; n = 44,188), sodium-glucose cotransporter 2 inhibitors (SGLT2i; n = 47,094), dipeptidyl peptidase-4 inhibitors (DPP4i; n = 84,315) and sulfonylureas (n = 210,679). Compared to DPP4i, GLP-1RA (hazard ratio (HR) 0.87; 95% confidence interval (CI) 0.82-0.93) and SGLT2i (HR 0.85; 95% CI 0.81-0.90) were associated with a lower risk of a major adverse cardiovascular event, whereas sulfonylureas were associated with a higher risk (HR 1.19; 95% CI 1.16-1.22). Thus, GLP-1RA and SGLT2i may be the preferred glucose-lowering agents for cardiovascular risk reduction in patients at moderate baseline risk for CVD. ClinicalTrials.gov registration: NCT05214573.
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Individuals with type 2 diabetes and moderate levels of CVD risk appear to derive cardiovascular and mortality benefits with preferential use of GLP-1 RA and SGLT2 inhibitors compared with sulfonylurea or DPP-4 inhibitors.
“Individuals with type 2 diabetes and moderate levels of CVD risk appear to derive cardiovascular and mortality benefits with preferential use of GLP-1 RA and SGLT2 inhibitors compared with sulfonylurea or DPP-4 inhibitors (134).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [134]
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9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
Self-citationNdumele, C. E., Rodriguez, F., Dixon, D. L., Khan, S. S., Mukherjee, D., Bajaj, M., Bangalore, S., Bozkurt, B., Breathett, K., Clarke, S. L., et al. (2026) · JACC · doi:10.1016/j.jacc.2026.03.056 · Cited by 90 · see citing works
- Authors
- McCoy, R. G., Herrin, J., Swarna, K. S., Deng, Y., Kent, D. M., Ross, J. S., Umpierrez, G. E., Galindo, R. J., Crown, W. H., Borah, B. J., Montori, V. M., Brito, J. P., Neumiller, J. J., Mickelson, M. M., & Polley, E. C.
- Affiliations
- University of Maryland, Baltimore (US)
- Yale University (US)
- Mayo Clinic (US)
- Tufts Medical Center (US)
- Emory University (US)
- University of Miami (US)
- Brandeis University (US)
- Washington State University Spokane (US)
- University of Chicago (US)
- Corresponding author
- McCoy, Rozalina G.
- ORCID
- Venue
- Nature Cardiovascular Research
- Published
- 2024-04-03
- Volume
- 3
- Issue
- 4
- Pages
- 431-440
- ISSN
- 2731-0590 (ISSN-L)
- PMC
- PMC11156225
- OpenAlex
- W4393851103
- Cited by
- 30
- References
- 9
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 3
- FWCI
- 9.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Cardiovascular Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Patient-Centered Outcomes Research Institute (PCS-1409-24099)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- type 2 diabetes, cardiovascular risk, major adverse cardiovascular events, glucose-lowering medications, GLP-1 receptor agonists, SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, comparative effectiveness, cardiovascular risk reduction
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