What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes (n=616297). Intervention: SGLT2 inhibitors and GLP1-RAs vs. Other 2nd-line antidiabetic therapies. Primary outcome: Incident CVD outcomes, including acute myocardial infarction, ischemic heart disease, heart failure, and stroke/TIA (HR 0.80, 95% CI 0.79-0.81).

June 7, 2026

2200-P: Real-World Effectiveness of Novel Antidiabetic Medications on Cardiovascular Outcomes among Medicare Beneficiaries by Race

Key Result

SGLT2i and GLP1-RA use were associated with 20% (HR 0.80; 95% CI 0.79-0.81) and 15% (HR 0.85; 95% CI 0.83-0.86) lower risks of incident CVD compared to other 2nd-line therapies in older adults.

Key Points

To evaluate the real-world effectiveness of newer antidiabetic medications on cardiovascular outcomes among older adults, focusing on racial differences.
Retrospective cohort study of Medicare beneficiaries aged ≥65 with type 2 diabetes from 2014 to 2019
Included a 100% sample of American Indian/Alaska Native beneficiaries and 20% random sample of other racial groups
Cox proportional hazards models with propensity score weighting estimated hazard ratios for cardiovascular disease outcomes.
SGLT2i users had a 20% lower cardiovascular risk (HR 0.80, 95% CI: 0.79-0.81) compared to other therapies.
GLP1-RA users had a 15% lower cardiovascular risk (HR 0.85, 95% CI: 0.83-0.86) compared to other therapies.
Stronger cardiovascular risk reductions were observed in Hispanic (30% and 35%), AI/AN (35% and 29%), and Black (32% and 27%) adults compared to White counterparts.

Study Design

Type

Cohort (n=616,297)

Multicenter

Yes

Structured PICO

Do SGLT2 inhibitors and GLP1 receptor agonists reduce incident cardiovascular disease compared to other 2nd-line antidiabetic therapies in older adults with type 2 diabetes?

Population

616,297 Medicare beneficiaries aged ≥65 years with type 2 diabetes from 21 U.S. states, followed from 2014-2019 through 2022.

Exposure

Initiation of SGLT2 inhibitors (n=47,847) or GLP1 receptor agonists (n=45,735), regardless of metformin use.

Comparator

Initiation of other 2nd-line antidiabetic therapies (n=573,309).

Outcome

Incident cardiovascular disease (CVD) outcomes, including acute myocardial infarction, ischemic heart disease, heart failure, and stroke/TIA.composite

In older adults with type 2 diabetes, SGLT2 inhibitors and GLP1 receptor agonists are associated with significantly reduced cardiovascular risk compared to other second-line therapies, with particularly strong benefits observed in racial minority groups.

Main Result

Hazard Ratio: 0.8 (95% CI 0.79–0.81)

Abstract

Introduction and Objective: Although clinical trials have demonstrated cardiovascular benefits of newer glucose-lowering agents, their real-world effectiveness for cardiovascular disease (CVD) prevention in older adults, and potential heterogeneity across racial groups, remain uncertain. Methods: We conducted a retrospective cohort study of Medicare beneficiaries aged ≥65 years with type 2 diabetes (T2D) from 21 U.S. states who were enrolled in Medicare Parts A, B, and D from 2014 to 2019, with follow-up through 2022. The study included a 100% sample of American Indian/Alaska Native (AI/AN) beneficiaries and a 20% random sample of other racial groups. Treatment cohorts included initiators of SGLT2i, GLP1-RAs, or other 2nd-line antidiabetic therapies, regardless of metformin use. Incident CVD outcomes, including acute myocardial infarction, ischemic heart disease, heart failure, and stroke/TIA, were identified using ICD9/10 codes. Cox proportional hazards models with propensity score weighting estimated hazard ratios (HRs) for incident CVD associated with SGLT2i and GLP1-RA use compared with other therapies, stratified by race. Results: Among 616,297 adults (mean age 67.6±10.1 years; 49.6% female), 5.1% were AI/AN, 5.6% Asian, 11.4% Black, 18.9% Hispanic, 56.3% White, and 2.7% others. Overall, 47,847, 45,735, 573,309 initiated SGLT2i, GLP1-RAs, and other 2nd-line therapies, respectively. Compared with other agents, SGLT2i use was associated with a 20% lower CVD risk (HR 0.80, 95% CI: 0.79-0.81) and GLP1-RAs a 15% lower CVD risk (HR 0.85, 95% CI: 0.83-0.86). SGLT2i and GLP1-RAs showed stronger CVD risk reduction among Hispanic (30% and 35%), AI/AN (35% and 29%), and Black (32% and 27%) adults than that among their White counterparts. Conclusion: In older adults with T2D, SGLT2i and GLP1-RAs were associated with significantly reduced CVD risk compared to other 2nd-line therapies, particularly among racial minority groups, highlighting their potential to reduce CVD burden and disparities in the real-world settings. Disclosure W. Fan: None. J. Dai: None. Y. Shi: None. J. OConnell: None. S.M. Manson: None. L. Jiang: None. Funding American Diabetes Association (CDTR-21)

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