Clinical application of glucagon-like peptide-1 receptor agonists in cardiovascular disease: lessons from recent clinical cardiovascular outcomes trials

Jun 14, 2018Cardiovascular diabetology

Using drugs that activate GLP-1 receptors for heart disease: insights from recent clinical trials

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Abstract

New antidiabetic agents may significantly influence cardiovascular outcomes in diabetes care.

Some glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with a marked risk reduction in major adverse cardiovascular events (MACE) in high-risk type 2 diabetes patients.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors and GLP-1RAs differ in their effects on cardiovascular outcomes, with SGLT2 inhibitors primarily reducing heart failure-related events.
GLP-1RAs may reduce atherosclerotic events, suggesting different mechanisms of cardiovascular benefit between the two drug classes.
The observed differences in cardiovascular benefits could inform tailored treatment plans based on individual patient cardiovascular risk and clinical conditions.

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Recent clinical trials investigating cardiovascular (CV) safety of newer antidiabetic agents have been rapidly and largely changing the landscape of diabetes care and providing highly important clinical information on decision-making regarding the choice of antidiabetic agents. Similar to the sodium-glucose cotransporter 2 (SGLT2) inhibitors, some glucagon-like peptide-1 receptor agonists (GLP-1RAs) have also demonstrated a marked risk reduction in major adverse CV events (MACE) in patients with type 2 diabetes at high risk of CV events. However, the two classes of agents differ largely in their pharmacological modes of action on glucose-lowering and CV parameters. Furthermore, CV benefits on individual components of MACE and other outcomes, including heart failure (HF), appear to differ partly between the two classes. Specifically, improvement of overall CV outcomes was likely driven by reduction in HF-related events in trials investigating SGLT2 inhibitors, and by reduction in atherosclerotic events in those investigating GLP-1RAs. This difference in CV benefit observed in the trials has important clinical implications regarding how to use the two classes of agents and how to identify suitable patients to obtain the best benefit from each class during routine diabetes care, possibly leading to a treatment plan tailored to an individual patient's CV risk and clinical condition. At this stage, however, we cardiologists may overlook such differences and may be unfamiliar with GLP-1RAs specifically. Herein, we highlight the potential benefits of GLP-1RAs on CV parameters observed in recent CV outcomes trials and further discuss clinical application of GLP-1RAs in CV medicine.

Full Text

What this is

Recent trials show glucagon-like peptide-1 receptor agonists (GLP-1RAs) can reduce cardiovascular (CV) events in high-risk type 2 diabetes patients.
GLP-1RAs differ from sodium-glucose cotransporter 2 (SGLT2) inhibitors in their effects on CV outcomes.
Understanding these differences is crucial for tailoring diabetes treatment to individual patient risks.

Essence

GLP-1RAs have demonstrated a significant reduction in major adverse cardiovascular events among patients with type 2 diabetes at high risk. Their mechanisms differ from SGLT2 inhibitors, emphasizing the need for tailored treatment strategies.

Key takeaways

GLP-1RAs reduce major adverse cardiovascular events (MACE) in high-risk type 2 diabetes patients. This contrasts with SGLT2 inhibitors, which primarily improve heart failure outcomes.
The distinct mechanisms of action between GLP-1RAs and SGLT2 inhibitors necessitate careful patient selection to maximize cardiovascular benefits in diabetes management.

Caveats

Cardiologists may be unfamiliar with GLP-1RAs, potentially leading to underutilization in clinical practice. Further education is needed to optimize patient outcomes.

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Authors’ contributions

AT wrote the draft of the article, which was critically supervised by KN. Both authors read and approved the final manuscript.

Acknowledgements

Authors thank Ms. Aya Yamada for her excellent secretarial assistance.

Competing interests

AT has no financial interests to disclose related to this manuscript. KN has received honoraria from Boehringer Ingelheim, Daiichi Sankyo, Mitsubishi Tanabe, Astellas, Merck, Takeda, and Ono; research funding from Teijin, Mitsubishi Tanabe, Boehringer Ingelheim, Astellas, and Bayer; and scholarships from Astellas, Daiichi Sankyo, Takeda, Mitsubishi Tanabe, Boehringer Ingelheim, Bristol-Myers Squibb, and Teijin.

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Abbreviations

Contributor Information

Atsushi Tanaka, Phone: +81-952-34-2364, Email: tanakaa2@cc.saga-u.ac.jp.

Koichi Node, Email: node@cc.saga-u.ac.jp.

References

Associated Data

Data Availability Statement

Not applicable.

Clinical application of glucagon-like peptide-1 receptor agonists in cardiovascular disease: lessons from recent clinical cardiovascular outcomes trials

Abstract

Full Text

What this is

Essence

Key takeaways

Caveats

Authors’ contributions

Acknowledgements

Competing interests

Availability of data and materials

Consent for publication

Ethics approval and consent to participate

Funding

Publisher’s Note

Abbreviations

Contributor Information

References

Associated Data

Data Availability Statement

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Abstract

Full Text

What this is

Essence

Key takeaways

Caveats

Authors’ contributions

Acknowledgements

Competing interests

Availability of data and materials

Consent for publication

Ethics approval and consent to participate

Funding

Publisher’s Note

Abbreviations

Contributor Information

References

Associated Data

Data Availability Statement

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the glp-1 therapies brief