Real-world Danish study confirms GLP-1 drugs reduce cardiovascular death and MACE over 3.5 years versus DPP-4i | Research

The takeaway

In 25,753 Danish T2DM patients matching LEADER criteria, sustained GLP-1RA use reduced 3P-MACE by 2.5%, cardiovascular mortality by 2.3%, and all-cause mortality by 2.5% versus DPP-4i over 3.5 years.

2.5% absolute MACE reduction
Danish real-world data confirms the LEADER trial finding that sustained GLP-1RA use reduces major cardiovascular events in T2DM patients at CV risk

What the researchers found

3P-MACE: -2.5% (95% CI 0.8-4.1%). CV mortality: -2.3% (1.4-3.1%). All-cause mortality: -2.5% (0.7-4.3%). HF: -0.9% (0.01-1.8%). Angina: -0.7% (0.01-1.3%). MI, stroke, revasc: NS. 6,681 GLP-1RA + 19,072 DPP-4i.

Why it matters

This confirms LEADER trial findings in real-world settings using rigorous causal inference methods, strengthening the evidence for GLP-1 drugs as cardiovascular protectors in everyday clinical practice.

How the study worked

Target trial emulation using Danish nationwide registries (2012-2022). LEADER-matching criteria. Longitudinal TMLE adjusting for baseline and time-varying confounding. DPP-4i as active comparator.

What this study cannot tell us

Observational despite causal inference methods. Danish population may not represent all demographics. DPP-4i comparator may have own CV effects. MI and stroke individually NS.

How to read the evidence

Target trial emulation with TMLE—among the strongest observational evidence designs. Nationwide data adds generalizability.

When this study was published

Published in 2025; data 2012-2022.

The bigger picture

Target trial emulation provides stronger causal evidence than typical observational studies. This Danish nationwide confirmation of LEADER adds to the global evidence base supporting GLP-1RA cardiovascular benefits.

Questions still open

Why were MI and stroke not significant individually while composite MACE was?
Do specific GLP-1RAs differ in real-world CV effectiveness?
Should the LEADER criteria define the GLP-1RA-eligible population?

Common questions

Do GLP-1 drugs really prevent heart attacks and death?

This large Danish real-world study confirms what clinical trials showed: sustained use of GLP-1 drugs reduces major cardiovascular events by 2.5%, cardiovascular death by 2.3%, and overall death by 2.5% over 3.5 years compared to DPP-4 inhibitors in diabetic patients at cardiovascular risk.

How is this different from a clinical trial?

Clinical trials have strict enrollment criteria and controlled conditions. This study used real-world data from over 25,000 Danish patients in everyday clinical practice, confirming that the benefits seen in controlled trials translate to actual patient outcomes.

Read the original research

Real-world cardiovascular effectiveness of sustained glucagon-like peptide 1 GLP-1 receptor agonist usage in type 2 diabetes.

Cardiovascular diabetology, 24(1), 385

View on PubMed ↗Publisher’s paper ↗

Citation

Sørensen, Kathrine Kold; Yazdanfard, Puriya Daniel Würtz; Zareini, Bochra; Pedersen-Bjergaard, Ulrik; Kosjerina, Vanja; Andersen, Mikkel Porsborg; Munch, Anders; Ohlendorff, Johan Sebastian; Schmid, Stefanie; Lanzinger, Stefanie; Choudhary, Pratik; Gillies, Clare; Gharibzadeh, Safoora; Lind, Marcus; Tasselius, Viktor; Michelsen, Jens; Gerds, Thomas Alexander; Torp-Pedersen, Christian. (2025). Real-world cardiovascular effectiveness of sustained glucagon-like peptide 1 GLP-1 receptor agonist usage in type 2 diabetes.. Cardiovascular diabetology, 24(1), 385. https://doi.org/10.1186/s12933-025-02915-1