{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T16:01:33Z","timestamp":1788537693328,"version":"build-2803163510"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2025,8,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) and sodium\u2013glucose cotransporter\u20102 inhibitors (SGLT2is) have favorable cardiovascular outcomes compared with dipeptidyl peptidase\u20104 inhibitors (DPP4is) and sulfonylureas in adults with type 2 diabetes and high cardiovascular risk. How these benefits vary across lower levels of cardiovascular risk is unknown.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods<\/jats:title>\n            <jats:p xml:lang=\"en\">We used nationwide claims data to emulate a comparative effectiveness trial and examine the heterogeneity of treatment effects of GLP\u20101RAs, SGLT2is, DPP4is, and sulfonylureas on major adverse cardiovascular events (MACEs) among adults with type 2 diabetes and moderate cardiovascular risk (annualized MACE risk 1%\u20135%, estimated using the annualized claims\u2010based MACE estimator).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Results<\/jats:title>\n            <jats:p xml:lang=\"en\">Among 386\u2009276 included adults with type 2 diabetes, 25.2% had baseline ACME\u2013predicted MACE risk &gt;1% to \u22642% (lower\u2010risk patients) and 13.3% had ACME\u2013predicted risk &gt;4% to \u22645% (higher\u2010risk patients). By year 3 of treatment, higher\u2010risk patients derived greater absolute benefit than lower\u2010risk patients when treated with GLP\u20101RAs versus sulfonylureas (absolute reduction in the estimated rate of MACE of 3.1% in higher\u2010risk patients and 1.6% in lower\u2010risk patients), SGLT2is versus sulfonylureas (absolute reduction, 3.9% in higher\u2010risk patients and 1.3% in lower\u2010risk patients), and GLP\u20101RAs versus DPP4is (absolute reduction, 1.6% in higher\u2010risk patients and 0.5% in lower\u2010risk patients). The relative benefits for MACE were also greater in higher\u2010risk than lower\u2010risk patients with SGLT2is versus DPP4is (hazard ratio [HR], 0.78 [95% CI, 0.70\u20130.87] in higher\u2010risk patients; HR, 0.99 [95% CI, 0.88\u20131.12] in lower\u2010risk patients). Conversely, the relative benefits of DPP4is and GLP\u20101RAs versus sulfonylureas were greater in lower\u2010risk patients: HR 0.76 (95% CI, 0.71\u20130.81) in lower\u2010risk and HR 0.91 (95% CI, 0.97\u20130.96) in higher\u2010risk patients for DPP4is versus sulfonylureas; HR 0.67 (95% CI, 0.58\u20130.78) in lower\u2010risk and HR 0.80 (95% CI, 0.70\u20130.93) in higher\u2010risk patients for GLP\u20101RAs versus sulfonylurea. Benefits of SGLT2is and GLP\u20101RAs were comparable across all risk levels.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Cardiovascular benefits of SGLT2is and GLP\u20101RAs exist across all levels of moderate cardiovascular risk, reinforcing the importance of choosing glucose\u2010lowering therapies that can prevent MACE in all people with type 2 diabetes.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.124.040217","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T12:02:12Z","timestamp":1752753732000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Heterogeneity of Cardiovascular Effects of Second\u2010Line Glucose\u2010Lowering Therapies in Adults With Type 2 Diabetes Across the Range of Moderate Baseline Cardiovascular Risk"],"prefix":"10.1161","volume":"14","author":[{"given":"Yihong","family":"Deng","sequence":"first","affiliation":[{"name":"Mayo Clinic Robert D. and Patricia E. 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Kern Center for the Science of Health Care Delivery","place":["Rochester, USA"]},{"name":"OptumLabs","place":["Eden Prairie, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9205-5070","authenticated-orcid":false,"given":"David M.","family":"Kent","sequence":"additional","affiliation":[{"name":"Tufts Medical Center","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9218-3320","authenticated-orcid":false,"given":"Joseph S.","family":"Ross","sequence":"additional","affiliation":[{"name":"Yale School of Medicine","place":["New Haven, USA"]},{"name":"Yale School of Public Health","place":["New Haven, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-764X","authenticated-orcid":false,"given":"Bradley A.","family":"Maron","sequence":"additional","affiliation":[{"name":"University of Maryland Institute for Health Computing","place":["North Bethesda, USA"]},{"name":"University of Maryland School of Medicine","place":["Baltimore, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3664-127X","authenticated-orcid":false,"given":"Mindy M.","family":"Mickelson","sequence":"additional","affiliation":[{"name":"Mayo Clinic Robert D. and Patricia E. 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