PeptideJournal
Research15 min read

GLP-1 Agonists & Cardiovascular Outcomes: Meta-Analysis

For years, diabetes medications were judged by one metric: how well they lowered blood sugar. That changed in 2008, when the FDA began requiring cardiovascular outcome trials (CVOTs) for new diabetes drugs -- and what followed has reshaped not just diabetes care, but cardiology itself.

For years, diabetes medications were judged by one metric: how well they lowered blood sugar. That changed in 2008, when the FDA began requiring cardiovascular outcome trials (CVOTs) for new diabetes drugs -- and what followed has reshaped not just diabetes care, but cardiology itself.

GLP-1 receptor agonists, originally developed to manage blood glucose by mimicking a gut hormone, turned out to do something unexpected. Trial after trial showed they didn't just avoid cardiovascular harm -- they actively reduced heart attacks, strokes, and cardiovascular deaths. The effect was consistent enough that these drugs are now recommended for cardiovascular protection independent of blood sugar control.

This article breaks down the evidence from every major CVOT, the meta-analyses that pool their data, the biological mechanisms behind the cardiovascular benefits, and what it all means for clinical practice. Whether you're trying to understand what semaglutide, liraglutide, or dulaglutide actually did in their landmark trials, this is the full picture.

Table of Contents

Understanding GLP-1 Receptor Agonists {#understanding-glp-1-receptor-agonists}

GLP-1 (glucagon-like peptide-1) is a hormone your gut releases after eating. It stimulates insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite. GLP-1 receptor agonists are synthetic versions of this hormone, engineered to last much longer in the body than natural GLP-1, which breaks down within minutes.

The class includes several approved medications:

  • Liraglutide (Victoza/Saxenda) -- once-daily injection
  • Semaglutide (Ozempic/Wegovy/Rybelsus) -- once-weekly injection or daily oral tablet
  • Dulaglutide (Trulicity) -- once-weekly injection
  • Exenatide (Byetta/Bydureon) -- twice-daily or once-weekly injection
  • Albiglutide (Tanzeum) -- once-weekly injection (discontinued commercially)
  • Lixisenatide (Adlyxin) -- once-daily injection

While all of these activate the GLP-1 receptor, their molecular structures, pharmacokinetics, and clinical profiles differ -- and so do their cardiovascular outcomes data.

The Major Cardiovascular Outcome Trials {#the-major-cardiovascular-outcome-trials}

Each CVOT measured the same primary endpoint: MACE (major adverse cardiovascular events), defined as a three-point composite of cardiovascular death, non-fatal myocardial infarction (heart attack), and non-fatal stroke. Trials enrolled thousands of patients with type 2 diabetes at high cardiovascular risk and followed them for years. Here's what each one found.

LEADER: Liraglutide {#leader-liraglutide}

The Trial: 9,340 patients with type 2 diabetes and high cardiovascular risk, randomized to liraglutide 1.8 mg daily or placebo, followed for a median of 3.8 years across 32 countries.

Primary Result: Liraglutide reduced MACE by 13% (HR 0.87; 95% CI 0.78-0.97; p=0.01).

Key Findings:

  • Cardiovascular death dropped by 22% (HR 0.78; 95% CI 0.66-0.93)
  • All-cause mortality dropped by 15% (HR 0.85; 95% CI 0.74-0.97)
  • Non-fatal MI and non-fatal stroke showed numerical reductions but didn't reach individual statistical significance

LEADER was the first GLP-1 agonist trial to demonstrate not just cardiovascular safety, but outright superiority. The all-cause mortality benefit was particularly notable -- few diabetes medications had ever shown that. European guidelines subsequently gave liraglutide a Class I, Level B recommendation for reducing the risk of death in patients with type 2 diabetes and cardiovascular disease.

SUSTAIN-6: Semaglutide (Injectable) {#sustain-6-semaglutide}

The Trial: 3,297 patients with type 2 diabetes and established cardiovascular disease or cardiovascular risk factors, randomized to injectable semaglutide (0.5 mg or 1.0 mg weekly) or placebo for 104 weeks across 230 sites in 20 countries.

Primary Result: Semaglutide reduced MACE by 26% (HR 0.74; 95% CI 0.58-0.95; p=0.02).

Key Findings:

  • Non-fatal stroke showed the most dramatic reduction: 39% (HR 0.61; 95% CI 0.38-0.99)
  • Patients experienced meaningful weight loss and blood pressure reductions sustained over 2 years
  • The 26% MACE reduction was the largest seen in any GLP-1 agonist CVOT

SUSTAIN-6 was technically designed as a non-inferiority trial (to prove semaglutide wasn't harmful), but the superiority it demonstrated exceeded what many researchers expected. The magnitude of the stroke reduction attracted particular attention and set the stage for the even larger SELECT trial.

REWIND: Dulaglutide {#rewind-dulaglutide}

The Trial: 9,901 patients with type 2 diabetes, randomized to dulaglutide 1.5 mg weekly or placebo, followed for a median of 5.4 years at 371 sites across 24 countries. Uniquely, only 31.5% of participants had established cardiovascular disease -- the rest had risk factors only.

Primary Result: Dulaglutide reduced MACE by 12% (HR 0.88; 95% CI 0.79-0.99; p=0.026).

Key Findings:

  • Non-fatal stroke showed the strongest individual component reduction: 24% (HR 0.76; 95% CI 0.61-0.95)
  • Benefits were consistent in both patients with and without prior cardiovascular disease
  • 46.3% of participants were women -- higher than most CVOTs -- with consistent benefits across genders
  • Composite microvascular outcomes improved by 13% (HR 0.87), driven primarily by kidney protection

REWIND stands out for two reasons. First, it enrolled a population closer to the typical diabetes patient a primary care physician sees -- not just high-risk patients with established heart disease. Second, it had the longest follow-up of any GLP-1 agonist CVOT (5.4 years), providing reassurance about long-term benefits. Dulaglutide became the first GLP-1 agonist to show MACE reduction in a primarily primary prevention population.

HARMONY Outcomes: Albiglutide {#harmony-outcomes-albiglutide}

The Trial: 9,463 patients with type 2 diabetes and established cardiovascular disease, randomized to albiglutide (30-50 mg weekly) or placebo at 610 sites across 28 countries.

Primary Result: Albiglutide reduced MACE by 22% (HR 0.78; 95% CI 0.68-0.90; p<0.001 for superiority).

Key Findings:

  • The MACE result (7% vs. 9%) showed clear superiority over placebo
  • Modest HbA1c reduction (0.52-0.63% vs. placebo) and weight loss (0.83 kg at 16 months)
  • No increase in pancreatitis, pancreatic cancer, or medullary thyroid carcinoma
  • Post-hoc analyses showed no increased risk of atrial fibrillation

The irony of HARMONY Outcomes is that GSK announced it would discontinue albiglutide commercially before the trial results were even released. Despite never being available to benefit from its own positive data, the trial contributed important evidence that cardiovascular protection is not limited to a single molecule but appears across structurally different GLP-1 agonists.

EXSCEL: Exenatide {#exscel-exenatide}

The Trial: 14,752 patients with type 2 diabetes (73.1% with prior cardiovascular disease), randomized to exenatide extended-release 2 mg weekly or placebo at 687 sites in 35 countries.

Primary Result: Exenatide showed a nominal 9% MACE reduction (HR 0.91; 95% CI 0.83-1.00; p<0.001 for non-inferiority; p=0.06 for superiority). Non-inferiority was confirmed, but superiority was not.

Key Findings:

  • All-cause mortality showed a nominal 14% reduction (HR 0.86; p=0.016), but this couldn't be formally claimed due to the prespecified statistical testing hierarchy
  • The trial confirmed cardiovascular safety of exenatide
  • In patients with preexisting cardiovascular disease, benefits appeared more pronounced

EXSCEL is often characterized as a "neutral" trial, but the picture is more nuanced. The direction of all endpoints favored exenatide, and the all-cause mortality signal was notable. Some researchers have argued that the pragmatic trial design, which allowed for more open-label GLP-1 agonist use in the placebo group, may have diluted the true treatment effect.

SELECT: Semaglutide in Obesity Without Diabetes {#select-semaglutide-obesity}

The Trial: 17,604 patients aged 45 and older with established cardiovascular disease and BMI of 27 or above -- but no diabetes -- randomized to semaglutide 2.4 mg weekly or placebo, with a mean exposure of 33 months.

Primary Result: Semaglutide reduced MACE by 20% (HR 0.80; 95% CI 0.72-0.90; p<0.001).

Key Findings:

  • MACE rates: 6.5% (semaglutide) vs. 8.0% (placebo)
  • Heart failure hospitalization dropped by 18% (HR 0.82; 95% CI 0.71-0.96)
  • All-cause mortality dropped by 19% (HR 0.81; 95% CI 0.71-0.93)
  • Mean weight loss at 104 weeks: 9.4% vs. 0.9%
  • Cardiovascular protection appeared independent of baseline adiposity and weight loss, suggesting mechanisms beyond fat reduction

SELECT was a watershed moment. It proved that the cardiovascular benefits of GLP-1 agonists extend beyond diabetes -- into the much larger population of people with obesity and heart disease. Importantly, a prespecified analysis published in The Lancet, 2025 showed that the cardiovascular benefits were independent of baseline adiposity measurements and had only a small association with waist circumference changes, pointing to direct vascular protection beyond weight loss.

Meta-Analysis Findings: The Combined Evidence {#meta-analysis-findings}

Individual trials tell individual stories. Meta-analyses tell us the story of the whole drug class. Multiple large pooled analyses published between 2024 and 2025 paint a remarkably consistent picture.

The Key Numbers

Badve et al. (Lancet Diabetes & Endocrinology, January 2025) pooled 11 trials with 85,373 participants:

  • MACE reduction: 14% (HR 0.86; 95% CI 0.80-0.92)
  • All-cause mortality reduction: 13% (HR 0.87; 95% CI 0.82-0.91)
  • Effects were consistent whether the SELECT trial (non-diabetic population) was included or not

Lee et al. (Diabetes Care, May 2025) analyzed 10 trials with 71,351 participants, including new data from the SOUL trial (oral semaglutide) and the FLOW trial:

  • MACE reduction: 14% (HR 0.86; 95% CI 0.81-0.90)
  • Heart failure hospitalization: 14% reduction (HR 0.86; 95% CI 0.79-0.93)
  • Composite kidney outcome: 17% reduction (HR 0.83; 95% CI 0.75-0.92)
  • All-cause mortality: 12% reduction (HR 0.88; 95% CI 0.82-0.93)
  • No significant difference between injectable and oral formulations

Kalayci et al. (European Heart Journal -- Cardiovascular Pharmacotherapy, 2025) evaluated 10 trials with 67,769 patients:

  • MACE reduction: 13% (OR 0.87; 95% CI 0.81-0.93; p<0.001)
  • Cardiovascular death: 14% reduction (OR 0.86; 95% CI 0.79-0.94)
  • All-cause mortality: 13% reduction (OR 0.87; 95% CI 0.82-0.94)

Individual MACE Components

When you break MACE apart into its three components, all three show consistent reductions:

OutcomeRelative Risk ReductionHazard Ratio
Cardiovascular death12-14%0.86-0.88
Non-fatal MI9-16%0.84-0.91
Non-fatal stroke13-15%0.85-0.87

The stroke signal is particularly strong. A dedicated stroke meta-analysis across 11 RCTs with 85,373 patients found a 15% reduction in total stroke (OR 0.85; 95% CI 0.77-0.93) and a 13% reduction in non-fatal stroke (OR 0.87; 95% CI 0.79-0.95), though fatal stroke risk was unchanged (ScienceDirect, 2025).

Non-Diabetic Obesity

In trials involving non-diabetic obese patients (16 trials, 23,467 participants), GLP-1 agonists reduced MACE by 20% (RR 0.80; 95% CI 0.72-0.89), with non-fatal stroke showing the largest individual reduction at 28%.

Mechanisms: How GLP-1 Agonists Protect the Heart {#mechanisms}

A 14% MACE reduction doesn't come from blood sugar control alone. The cardiovascular protection seen with GLP-1 agonists involves multiple overlapping biological pathways that researchers are still untangling.

Anti-Inflammatory Effects

Chronic inflammation drives atherosclerosis -- the buildup of fatty plaques in arteries that eventually causes heart attacks and strokes. GLP-1 receptor agonists appear to intervene at several points in this inflammatory cascade:

  • They suppress the NLRP3 inflammasome, a key inflammatory signaling complex involved in plaque instability
  • They shift macrophages (immune cells in arterial walls) toward an anti-inflammatory M2 phenotype, producing a more stable plaque environment
  • Clinical trials have documented reductions in circulating inflammatory markers including TNF-alpha, IL-6, and IL-1-beta in patients treated with dulaglutide, liraglutide, and exenatide

Importantly, preclinical studies suggest the anti-atherosclerotic effect is independent of plasma lipid changes and depends primarily on this anti-inflammatory response (American Journal of Physiology, 2024).

Endothelial Function

The endothelium -- the thin layer of cells lining every blood vessel -- is the first point of contact between blood and the arterial wall. Endothelial dysfunction is one of the earliest steps in atherosclerosis. GLP-1 agonists improve endothelial health through several pathways:

  • They stimulate nitric oxide (NO) production by activating endothelial nitric oxide synthase (eNOS), which causes blood vessels to relax and dilate
  • They reduce oxidative stress in the vascular wall, preventing the damage that triggers plaque formation
  • They lower expression of adhesion molecules (VCAM-1, ICAM-1) on endothelial cells, blocking the initial attachment of immune cells that starts the atherosclerotic process

Anti-Atherosclerotic Actions

GLP-1 receptor agonists target multiple stages of plaque development:

  • Foam cell prevention: They activate cholesterol efflux pathways (via ABCA1) in macrophages, preventing the lipid-laden foam cells that are the building blocks of plaques
  • Plaque stabilization: In human carotid plaque samples, GLP-1 therapy was associated with higher collagen content and less inflammation, producing more stable plaques less likely to rupture
  • Novel delivery research: Scientists have even developed plaque-targeted nanoparticles loaded with GLP-1 agonists (GlpNP) that selectively accumulate in atherosclerotic plaques and reduce their burden, demonstrating that GLP-1 can act directly on plaques independent of metabolic effects

Metabolic and Systemic Effects

On top of these direct vascular effects, GLP-1 agonists improve multiple traditional cardiovascular risk factors:

  • Weight loss: 5-15% body weight reduction depending on dose and duration
  • Blood pressure: Systolic blood pressure reductions of 2-6 mmHg
  • Lipid profiles: Modest improvements in triglycerides and LDL cholesterol
  • Kidney protection: 17% reduction in composite kidney outcomes, including kidney failure

The current scientific consensus is that cardiovascular protection results from all these mechanisms working together -- a "multi-pronged" effect that no single pathway fully explains (Journal of Clinical Medicine, 2025).

Subgroup Analyses: Who Benefits Most? {#subgroup-analyses}

Not everyone benefits equally from GLP-1 agonists, and meta-regression analyses have identified several factors that modify the cardiovascular benefit.

BMI and Adiposity

Patients with higher baseline BMI appear to get greater cardiovascular benefit. Meta-regression by Kalayci et al. found that each additional kg/m-squared of baseline BMI was associated with greater MACE reduction (logOR = -0.098 per kg/m-squared, p=0.006). However, the SELECT trial showed that benefits were not explained by weight loss itself, suggesting BMI may be a marker for greater metabolic dysregulation rather than a direct mediator.

Age

Older patients showed a stronger cardiovascular response (logOR = -0.033 per year, p=0.023), which may reflect a higher baseline cardiovascular risk offering more room for benefit.

Primary vs. Secondary Prevention

The REWIND trial proved that benefits extend to primary prevention populations (patients with risk factors but no prior cardiovascular events), though the absolute risk reduction is naturally smaller in lower-risk patients. The number needed to treat (NNT) was 72 in REWIND's primarily primary prevention population, compared to smaller NNTs in secondary prevention trials like SELECT.

Racial and Ethnic Differences

A 2025 systematic review in Diabetes Care found that Asian populations may derive greater cardiovascular benefits from GLP-1 agonists compared to White populations, though Asian participants typically represent less than 10% of CVOT enrollment, limiting the strength of this finding.

Heart Failure

One consistent limitation across trials: GLP-1 agonists have not shown clear benefits in patients with established heart failure with reduced ejection fraction (HFrEF). In EXSCEL, benefits on death and heart failure hospitalization were attenuated in patients with baseline heart failure. Post-hoc analysis from HARMONY Outcomes showed no effect on heart failure events in patients with heart failure history. This may reflect different pathophysiology in HFrEF versus atherosclerotic cardiovascular disease.

Clinical Implications and Guideline Recommendations {#clinical-implications}

The cardiovascular evidence has fundamentally changed how GLP-1 agonists are positioned in treatment guidelines.

Current Guideline Status

  • ESC (European Society of Cardiology): GLP-1 agonists with proven cardiovascular benefit (liraglutide, semaglutide, dulaglutide) receive a Class I, Level A recommendation for reducing cardiovascular events in patients with type 2 diabetes and cardiovascular disease or very high cardiovascular risk
  • Liraglutide specifically receives a Class I, Level B recommendation for reducing mortality risk
  • GLP-1 agonists are now recommended as first-line therapy (even before metformin) in patients with type 2 diabetes and atherosclerotic cardiovascular disease

Beyond Diabetes

The SELECT trial expanded the indication beyond type 2 diabetes. Semaglutide 2.4 mg received approval for cardiovascular risk reduction in patients with obesity and established heart disease -- regardless of diabetes status. In 2025, semaglutide gained EU approval as the first stroke management therapy based on the phase 3 SOUL trial data showing a 14% reduction in cardiovascular death, heart attack, and stroke in type 2 diabetes patients at high cardiovascular risk.

Safety Profile

Meta-analyses consistently show that GLP-1 agonists do not increase serious adverse events. There is no elevated risk of pancreatitis, pancreatic cancer, severe hypoglycemia, or retinopathy. The main tolerability concern is gastrointestinal side effects (nausea, vomiting, diarrhea), which lead to treatment discontinuation more often than placebo (RR 1.51 for discontinuation due to adverse events). These gastrointestinal effects typically diminish over weeks with continued use.

What's Coming Next for the GLP-1 Class

The cardiovascular story continues to expand. Newer molecules in the GLP-1 family, including the dual GIP/GLP-1 agonist tirzepatide and the triple agonist retatrutide, are being tested in their own cardiovascular outcome trials. Whether multi-agonists provide even greater cardiovascular protection remains one of the most watched questions in metabolic medicine.

Research also continues into the connections between GLP-1 agonists and other conditions, including neurodegeneration and kidney disease, further broadening the clinical significance of this drug class.

FAQ {#faq}

Do all GLP-1 agonists reduce cardiovascular events?

Not equally. Liraglutide, semaglutide, dulaglutide, and albiglutide have all shown statistically significant MACE reductions. Exenatide showed a trend toward benefit but did not reach statistical significance for superiority. Lixisenatide (ELIXA trial) showed no cardiovascular benefit or harm. The differences may reflect molecular properties, dosing, or trial design factors.

How much does weight loss explain the cardiovascular benefit?

Less than you might expect. While GLP-1 agonists cause significant weight loss, the SELECT trial showed cardiovascular protection was independent of baseline adiposity and only weakly associated with waist circumference changes. This points to direct vascular and anti-inflammatory effects beyond fat reduction.

Are the cardiovascular benefits the same with oral semaglutide?

The 2025 meta-analysis by Lee et al. found no significant difference in MACE reduction between injectable and oral GLP-1 agonist formulations. The SOUL trial, which tested oral semaglutide, contributed to this finding, though the oral form may have different pharmacokinetic considerations.

Should I take a GLP-1 agonist just for heart protection if I don't have diabetes?

The SELECT trial supports semaglutide 2.4 mg for cardiovascular risk reduction in people with obesity (BMI 27 or above) and established cardiovascular disease, regardless of diabetes status. This is a conversation to have with your doctor, weighing cardiovascular risk, side effect tolerance, cost, and individual clinical circumstances.

How quickly do the cardiovascular benefits appear?

In most trials, the survival curves for GLP-1 agonist and placebo groups began separating within the first 12 to 18 months, with benefits accumulating over time. This suggests the mechanisms (particularly anti-inflammatory and anti-atherosclerotic effects) need time to translate into event reduction.

What about heart failure -- do GLP-1 agonists help?

The data are mixed. While SELECT showed an 18% reduction in heart failure hospitalization, most trials have not shown clear benefits in patients who already have heart failure with reduced ejection fraction. GLP-1 agonists appear to work best against atherosclerotic disease (heart attacks, strokes) rather than the cardiomyopathy that underlies most heart failure.

The Bottom Line {#the-bottom-line}

The cardiovascular evidence for GLP-1 receptor agonists is now among the strongest for any drug class in cardio-metabolic medicine. Across six major CVOTs and multiple meta-analyses pooling over 85,000 patients, the signal is consistent: a 13-14% reduction in MACE, meaningful reductions in cardiovascular death and stroke, and emerging benefits for kidney protection and all-cause mortality.

What makes this evidence particularly compelling is that the benefits:

  • Are consistent across multiple molecules with different structures
  • Extend to patients without diabetes (SELECT trial)
  • Operate through direct vascular and anti-inflammatory mechanisms beyond metabolic improvements
  • Appear safe, with no increase in serious adverse events

The remaining questions are important but narrow: whether newer multi-agonists like tirzepatide will show even greater protection, whether cardiovascular benefits differ meaningfully across ethnic groups, and whether earlier intervention in lower-risk populations could provide cost-effective prevention.

For now, the evidence supports what guidelines already recommend: in patients with type 2 diabetes and cardiovascular disease, GLP-1 agonists with proven benefit should be a front-line consideration. And with SELECT's data, that conversation now extends to anyone with obesity and established heart disease.

References {#references}

  1. Marso SP, et al. "Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes." New England Journal of Medicine, 2016. (LEADER trial)

  2. Marso SP, et al. "Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes." New England Journal of Medicine, 2016. (SUSTAIN-6 trial)

  3. Gerstein HC, et al. "Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes (REWIND)." The Lancet, 2019.

  4. Hernandez AF, et al. "Albiglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes and Cardiovascular Disease (Harmony Outcomes)." The Lancet, 2018.

  5. Holman RR, et al. "Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes." New England Journal of Medicine, 2017. (EXSCEL trial)

  6. Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes." New England Journal of Medicine, 2023. (SELECT trial)

  7. Badve SV, et al. "Effects of GLP-1 Receptor Agonists on Kidney and Cardiovascular Disease Outcomes: A Meta-Analysis of Randomised Controlled Trials." Lancet Diabetes & Endocrinology, 2025.

  8. Lee MMY, et al. "Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral GLP-1 Receptor Agonists." Diabetes Care, 2025.

  9. Kalayci A, et al. "Clinical Features Modifying the Cardiovascular Benefits of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis." European Heart Journal -- Cardiovascular Pharmacotherapy, 2025.

  10. Lincoff AM, et al. "Semaglutide and Cardiovascular Outcomes by Baseline and Changes in Adiposity Measurements: A Prespecified Analysis of the SELECT Trial." The Lancet, 2025.

  11. Helmstadter J, et al. "GLP-1 Receptor Agonists and Atherosclerosis Protection: The Vascular Endothelium Takes Center Stage." American Journal of Physiology -- Heart and Circulatory Physiology, 2024.

  12. Ussher JR, Bhatt DL. "GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes." Circulation, 2023.

  13. Sattar N, et al. "Cardiovascular and Renal Outcomes of GLP-1 Receptor Agonists Among Patients With and Without Type 2 Diabetes Mellitus." ScienceDirect, 2024.

  14. Li Y, et al. "GLP-1 Agonists in Cardiovascular Diseases: Mechanisms, Clinical Evidence, and Emerging Therapies." Journal of Clinical Medicine, 2025.

  15. Tanaka H, et al. "Comparative Efficacy of GLP-1 Receptor Agonists for Cardiovascular Outcomes in Asian Versus White Populations." Diabetes Care, 2025.

  16. Mahapatra MK, et al. "The Expanding Role of GLP-1 Receptor Agonists: A Narrative Review of Current Evidence and Future Directions." PMC, 2025.