GLP-1s May Protect Against Cardiovascular Outcomes Regardless of Diabetes Status

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Research presented at the Heart Failure Society of America 2024 Annual Meeting demonstrated that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) reduced cardiovascular events in patients without diabetes.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may reduce the risk of heart failure hospitalization, mortality, and cardiovascular outcomes, even in individuals without diabetes, according to research presented at the Heart Failure Society of America 2024 Annual Meeting.1

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These findings build on existing evidence demonstrating the effectiveness of GLP-1 RAs in improving cardiovascular outcomes for patients with type 2 diabetes (T2D). To explore this potential benefit in a broader population, investigators conducted a meta-analysis of cardiovascular outcome trials to assess the effect of GLP-1 RAs on mortality and cardiovascular outcomes in patients without diabetes.

Using the Cochrane Central Registry of Controlled Trials, PubMed, Embase, and ClinicalTrials.gov, investigators gathered a total of 9 randomized controlled trials published until March 2024. The clinical outcomes of interest were all-cause mortality, cardiovascular death, heart failure hospitalization, myocardial infarction, revascularization, and stroke.

Of 77,684 participants included, 39,497 received GLP-1 RAs and 38,187 received placebo.

READ MORE: Higher Vaccination Rates Improve Outcomes in Heart Failure During Respiratory Virus Season

Compared to placebo, GLP-1 RA was associated with a significant reduction in all-cause mortality (95% CI: 0.82-0.92, P < .00001), cardiovascular death (95% CI: 0.81-0.93, P < .0001), myocardial infarction (95% CI: 0.79-0.97, P = .01), revascularization (95% CI: 0.74-0.94, P = .004), stroke (95% CI: 0.78-0.93, P = .0005), and heart failure hospitalization (95% CI: 0.82-0.97, P = .006).

Previously, topline results from the pivotal FLOW trial demonstrated that semaglutide (Ozempic) was able to reduce kidney disease progression, major adverse cardiovascular events (MACE), and death by 24% in patients with T2D.2 This positive effect was confirmed by secondary endpoints, leading to the early termination of the trial due to its demonstrated efficacy.

Another meta-analysis involving 83,258 patients corroborated these findings, demonstrating that GLP-1 RAs reduced MACE, overall and cardiovascular mortality, stroke, coronary revascularization, and composite kidney outcomes across various patient subgroups.3 These included sex, estimated glomerular filtration rates, body mass index, and history of cardiovascular disease, in patients with and without diabetes. As a result, authors of the meta-analysis, published in the American Journal of Preventive Cardiology, recommended that health care professionals consider prescribing GLP-1RAs to all eligible patients to improve cardiovascular and renal outcomes.

By demonstrating that GLP-1 RAs significantly reduced heart failure hospitalization, mortality, and cardiovascular events, regardless of diabetes status, the current study adds to this body of research. These findings could inform future guidelines for GLP-1RAs especially as they continue to grow in popularity. However, investigators noted that longer-term follow-up studies are necessary to determine if these improvements translate into increased overall survival.

Click here for more coverage of the Heart Failure Society of America 2024 Annual Meeting.

READ MORE: Diabetes Resource Center

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References
1. Sammudeen I. Cardiovascular outcomes of glucagon-like peptide 1 receptor agonists irrespective of diabetes status: A meta-analysis of randomized controlled trials. Presented at: Heart Failure Society of America 2024 Annual Meeting; September 27-30, 2024; Atlanta, GA. Poster 1437-324.
2. Myshko D. Ozempic lowers risk of kidney disease progression, cardiovascular events by 24%. Drug Topics. March 6, 2024. Accessed October 1, 2024. https://www.drugtopics.com/view/ozempic-lowers-risk-of-kidney-disease-progression-cardiovascular-events-by-24-
3. Rivera FB, Cruz LLA, Magalong JV, et al. Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials. Am J Prev Cardiol. 2024;18:100679. Published 2024 May 7. doi:10.1016/j.ajpc.2024.100679
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