State-of-the-art review: semaglutide reduces cardiovascular events in both diabetic and non-diabetic patients with heart and kidney disease | Research

The takeaway

Comprehensive review of semaglutide in ASCVD, HF, and diabetic nephropathy confirms MACE reduction in T2DM (SUSTAIN/PIONEER) and non-T2DM (SELECT), HFpEF symptom/hospitalization improvement (STEP-HFpEF), and renal protection (FLOW trial).

Complete CV evidence synthesis
Semaglutide reduces MACE in diabetic and non-diabetic ASCVD, improves HFpEF outcomes, and protects kidneys—the most comprehensive cardiorenal peptide drug evidence to date

What the researchers found

ASCVD: MACE reduction in T2DM + non-T2DM. HFpEF: improved symptoms, function, NPs, echo, ↓HF hospitalization. SELECT HF subanalysis: ↓CV mortality + HF hospitalization. FLOW: renal + CV benefits in diabetic nephropathy independent of BMI. Evidence gaps: HF without ASCVD, non-obese HF.

Why it matters

This is the most comprehensive single-source synthesis of semaglutide cardiovascular evidence, providing clinicians with a complete picture for prescribing decisions across cardiorenal diseases.

How the study worked

State-of-the-art narrative review of semaglutide cardiovascular and renal clinical trial evidence.

What this study cannot tell us

Review format. Dedicated HF trials without ASCVD criteria still needed. Non-obese HF patients not adequately studied. Long-term mortality data limited for HFpEF.

How to read the evidence

State-of-the-art review of major clinical trials. Strong evidence base with identified gaps.

When this study was published

Published in 2025.

The bigger picture

Semaglutide is evolving from a diabetes drug to a comprehensive cardiorenal protective agent with proven benefits across the entire spectrum of cardiometabolic disease.

Questions still open

Should semaglutide receive a formal HFpEF indication?
Will non-obese HF patients also benefit?
Is semaglutide the new standard of care for cardiorenal protection?

Common questions

Is semaglutide a heart drug now?

Increasingly, yes. This comprehensive review shows semaglutide reduces heart attacks and strokes in both diabetic and non-diabetic patients, improves heart failure symptoms and hospitalizations, and protects kidneys. It is evolving from a diabetes drug into a comprehensive cardiorenal protective agent.

Who should get semaglutide for heart protection?

Based on current evidence: patients with T2DM and cardiovascular disease (strongest evidence), obese patients with ASCVD without diabetes (SELECT trial), patients with HFpEF and obesity (STEP-HFpEF), and patients with diabetic kidney disease (FLOW trial). Evidence gaps remain for non-obese HF patients without ASCVD.

Read the original research

Semaglutide in heart failure and atherosclerotic cardiovascular disease: the current state-of-the-art.

Heart failure reviews, 30(4), 801-816

View on PubMed ↗Publisher’s paper ↗

Citation

Theodorakis, Nikolaos; Kreouzi, Magdalini; Nikolaou, Maria. (2025). Semaglutide in heart failure and atherosclerotic cardiovascular disease: the current state-of-the-art.. Heart failure reviews, 30(4), 801-816. https://doi.org/10.1007/s10741-025-10506-1