An overview of GLP-1 agonists and recent cardiovascular outcomes trials
Open accessAbstract
Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are emerging as an important therapy to consider for patients with type 2 diabetes (T2D) given this class of treatment's ability to reduce glycated haemoglobin and their associated weight loss and low risk for hypoglycaemia. Additionally, seven cardiovascular outcomes trials (CVOTs) have been performed in the past 4 years using lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide and oral semaglutide. All have found non-inferiority for cardiovascular outcomes, with many finding superiority of these drugs. These findings have transformed our guidelines on pharmacological treatment of T2D. This review article will discuss GLP-1 RA therapy, review the seven CVOTs reported to date and discuss the implications on current guidelines and therapies going forward.
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SGLT2i and GLP1ra significantly reduce cardiovascular deaths independent of their effect on hyperglycemia.
“Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) are novel classes of medications for type 2 diabetes that significantly reduce cardiovascular deaths independent of their effect on hyperglycemia and are widely endorsed by clinical practice guidelines.4–11”
From Disparities in Use of Novel Diabetes Medications by Insurance: A Nationally Representative Cohort Study (2024) · cites this paper as [7]
The LEADER section reports significantly fewer cardiovascular deaths with liraglutide than with placebo, and the guidelines discussion recommends considering GLP-1 RAs or SGLT2 inhibitors for some patients with type 2 diabetes. But the paper does not establish a cardiovascular-death reduction for both drug classes independent of glucose lowering; its SUSTAIN-6 section explicitly questions whether semaglutide’s cardiovascular benefit came from the drug itself or improved glycaemic control. No page numbers are available in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredSGLT2i and GLP1ra are widely endorsed by clinical practice guidelines.
“Sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1ra) are novel classes of medications for type 2 diabetes that significantly reduce cardiovascular deaths independent of their effect on hyperglycemia and are widely endorsed by clinical practice guidelines.4–11”
From Disparities in Use of Novel Diabetes Medications by Insurance: A Nationally Representative Cohort Study (2024) · cites this paper as [7]
Trials in people with type 2 diabetes have shown convincing reductions in cardiovascular events with some GLP-1 RA.
“Trials in people with type 2 diabetes have shown convincing reductions in cardiovascular events with some GLP-1 RA (259); whether these benefits would also be seen in people with type 1 diabetes is unknown.”
Seven trials have demonstrated superiority or almost non-inferiority of GLP-1 RAs for CV outcomes, indicating advantageous cardio-protective effects.
“In recent years, seven trials have demonstrated their superiority or almost non-inferiority for CV outcomes, indicating advantageous cardio-protective effects [170].”
From Dysregulated epicardial adipose tissue as a risk factor and potential therapeutic target of heart failure with preserved ejection fraction in diabetes (2022) · cites this paper as [170]
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- Authors
- Sheahan, K. H., Wahlberg, E. A., & Gilbert, M. P.
- Affiliations
- University of Vermont Medical Center (US)
- Corresponding author
- Sheahan, Kelsey H
- Venue
- Postgraduate Medical Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-12-04
- Volume
- 96
- Issue
- 1133
- Pages
- 156-161
- ISSN
- 0032-5473 (ISSN-L)
- 1469-0756
- PMC
- PMC7042958
- OpenAlex
- W2992144798
- Cited by
- 194
- References
- 26
- Citations by year
- 2026: 10 · 2025: 28 · 2024: 31 · 2023: 27 · 2022: 43 · 2021: 47 · 2020: 8
- FWCI
- 19.88
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Postgraduate Medical Journal (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Sanofi
- Max-Planck-Gesellschaft
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- GLP-1 receptor agonists, type 2 diabetes, lixisenatide, liraglutide, semaglutide, exenatide, albiglutide, dulaglutide, oral semaglutide, HbA1c, weight loss, hypoglycemia, treatment guidelines
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Cardiovascular Diseases, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Medication Therapy Management
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