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Background <p>Cardiovascular outcome trials have shown that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular event rates more effectively than placebo and in patients with type 2 diabetes at increased cardiovascular risk. However, the generalizability of these findings to real-world settings remains uncertain.</p> Aim <p>This study aimed to evaluate the real-world cardiovascular effectiveness of sustained GLP1-RA use compared to dipeptidyl peptidase 4 inhibitor (DPP-4i) over 3.5 years.</p> Methods <p>Using Danish nationwide registries, we emulated a target trial to assess the real-world effectiveness of GLP1-RAs in a population of individuals with type 2 diabetes mirroring the inclusion and exclusion criteria from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. The study period was 2012–2022. Outcomes included the composite of myocardial infarction, stroke, and cardiovascular mortality (3P-MACE), as well as each component individually, alongside all-cause mortality, heart failure, angina pectoris, and revascularization. Longitudinal Targeted Minimum Loss-based Estimation, a method that adjusts for both baseline and time-varying confounding, was used to estimate absolute risks of cardiovascular outcomes under sustained use of GLP1-RA and DPP 4i (active comparator), adjusting for baseline and time-varying confounding.</p> Results <p>We included 6,681 people initiating GLP1-RA and 19,072 initiating DPP-4i. Accounting for baseline and time-varying confounding, sustained GLP1-RA use showed a 2.5% (95% CI 0.8–4.1%) risk reduction of 3P-MACEover 3.5 years. Risk reductions for cardiovascular mortality, all-cause mortality, heart failure, and unstable angina pectoris were 2.3% (95% CI 1.4–3.1%), 2.5% (95% CI 0.7–4.3%), 0.9% (95% CI 0.01–1.8%), and 0.7% (95% CI 0.01–1.3%), respectively. No significant differences were observed for myocardial infarction, stroke, or revascularization with risk differences of 0.1% (95% CI −1.0 to 0.8%), 0.8% (95% CI −0.2 to 1.7%), and 0.2% (95% CI -0.7–1.1%), respectively.</p> Conclusions <p>This real-world study confirms the cardiovascular benefits of GLP1-RAs over DPP-4is, particularly for reducing cardiovascular and all-cause mortality under continuous treatment exposure in patients with type 2 diabetes at increased cardiovascular risk.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月6日

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  • Kathrine Kold Sørensen,
  • Puriya Daniel Würtz Yazdanfard,
  • Bochra Zareini,
  • Ulrik Pedersen-Bjergaard,
  • Vanja Kosjerina,
  • Mikkel Porsborg Andersen,
  • Anders Munch,
  • Johan Sebastian Ohlendorff,
  • Stefanie Schmid,
  • Stefanie Lanzinger,
  • Pratik Choudhary,
  • Clare Gillies,
  • Safoora Gharibzadeh,
  • Marcus Lind,
  • Viktor Tasselius,
  • Jens Michelsen,
  • Thomas Alexander Gerds,
  • Christian Torp-Pedersen

摘要

Background

Cardiovascular outcome trials have shown that glucagon-like peptide 1 receptor agonists (GLP1-RAs) reduce cardiovascular event rates more effectively than placebo and in patients with type 2 diabetes at increased cardiovascular risk. However, the generalizability of these findings to real-world settings remains uncertain.

Aim

This study aimed to evaluate the real-world cardiovascular effectiveness of sustained GLP1-RA use compared to dipeptidyl peptidase 4 inhibitor (DPP-4i) over 3.5 years.

Methods

Using Danish nationwide registries, we emulated a target trial to assess the real-world effectiveness of GLP1-RAs in a population of individuals with type 2 diabetes mirroring the inclusion and exclusion criteria from the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. The study period was 2012–2022. Outcomes included the composite of myocardial infarction, stroke, and cardiovascular mortality (3P-MACE), as well as each component individually, alongside all-cause mortality, heart failure, angina pectoris, and revascularization. Longitudinal Targeted Minimum Loss-based Estimation, a method that adjusts for both baseline and time-varying confounding, was used to estimate absolute risks of cardiovascular outcomes under sustained use of GLP1-RA and DPP 4i (active comparator), adjusting for baseline and time-varying confounding.

Results

We included 6,681 people initiating GLP1-RA and 19,072 initiating DPP-4i. Accounting for baseline and time-varying confounding, sustained GLP1-RA use showed a 2.5% (95% CI 0.8–4.1%) risk reduction of 3P-MACEover 3.5 years. Risk reductions for cardiovascular mortality, all-cause mortality, heart failure, and unstable angina pectoris were 2.3% (95% CI 1.4–3.1%), 2.5% (95% CI 0.7–4.3%), 0.9% (95% CI 0.01–1.8%), and 0.7% (95% CI 0.01–1.3%), respectively. No significant differences were observed for myocardial infarction, stroke, or revascularization with risk differences of 0.1% (95% CI −1.0 to 0.8%), 0.8% (95% CI −0.2 to 1.7%), and 0.2% (95% CI -0.7–1.1%), respectively.

Conclusions

This real-world study confirms the cardiovascular benefits of GLP1-RAs over DPP-4is, particularly for reducing cardiovascular and all-cause mortality under continuous treatment exposure in patients with type 2 diabetes at increased cardiovascular risk.