ArticleJournal of the American Heart Association2025
Heterogeneity of Cardiovascular Effects of Second-Line Glucose-Lowering Therapies in Adults With Type 2 Diabetes Across the Range of Moderate Baseline Cardiovascular Risk.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed, 1 synthesis or guideline pooled it.
- SGLT2 versus DPP-4 inhibitors in type 2 diabetes: a meta-analysis of outcomes.Frontiers in endocrinology · 2026Pooled it
- Comparative Effectiveness of Individual Sodium Glucose Transporter 2 Inhibitors on Cardiovascular Outcomes in Type 2 Diabetes With Moderate Cardiovascular Risk: Emulation of a Target Trial.Journal of the American Heart Association · 2026Article
- GLP-1RA precision medicine in people with type 2 diabetes: current insights and future prospects.The Journal of clinical investigation · 2026Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
backgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2is) have favorable cardiovascular outcomes compared with dipeptidyl peptidase-4 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.
methodsWe used nationwide claims data to emulate a comparative effectiveness trial and examine the heterogeneity of treatment effects of GLP-1RAs, SGLT2is, DPP4is, and sulfonylureas on major adverse cardiovascular events (MACEs) among adults with type 2 diabetes and moderate cardiovascular risk (annualized MACE risk 1%-5%, estimated using the annualized claims-based MACE estimator).
resultsAmong 386 276 included adults with type 2 diabetes, 25.2% had baseline ACME-predicted MACE risk >1% to ≤2% (lower-risk patients) and 13.3% had ACME-predicted risk >4% to ≤5% (higher-risk patients). By year 3 of treatment, higher-risk patients derived greater absolute benefit than lower-risk patients when treated with GLP-1RAs versus sulfonylureas (absolute reduction in the estimated rate of MACE of 3.1% in higher-risk patients and 1.6% in lower-risk patients), SGLT2is versus sulfonylureas (absolute reduction, 3.9% in higher-risk patients and 1.3% in lower-risk patients), and GLP-1RAs versus DPP4is (absolute reduction, 1.6% in higher-risk patients and 0.5% in lower-risk patients). The relative benefits for MACE were also greater in higher-risk than lower-risk patients with SGLT2is versus DPP4is (hazard ratio [HR], 0.78 [95% CI, 0.70-0.87] in higher-risk patients; HR, 0.99 [95% CI, 0.88-1.12] in lower-risk patients). Conversely, the relative benefits of DPP4is and GLP-1RAs versus sulfonylureas were greater in lower-risk patients: HR 0.76 (95% CI, 0.71-0.81) in lower-risk and HR 0.91 (95% CI, 0.97-0.96) in higher-risk patients for DPP4is versus sulfonylureas; HR 0.67 (95% CI, 0.58-0.78) in lower-risk and HR 0.80 (95% CI, 0.70-0.93) in higher-risk patients for GLP-1RAs versus sulfonylurea. Benefits of SGLT2is and GLP-1RAs were comparable across all risk levels.
conclusionsCardiovascular benefits of SGLT2is and GLP-1RAs exist across all levels of moderate cardiovascular risk, reinforcing the importance of choosing glucose-lowering therapies that can prevent MACE in all people with type 2 diabetes.
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