GLP-1 and Cardiovascular Health: SELECT Trial Evidence

The SELECT trial: landmark evidence for heart health

If you have a history of heart disease, stroke, or other cardiovascular events, you may be asking whether GLP-1 medications can help protect your heart. For one medication, in one group of people, there is now outcome-trial evidence.

In 2023, the New England Journal of Medicine published results from the SELECT trial, which examined whether semaglutide 2.4 mg, the dose used for weight management, reduces the risk of major cardiovascular events in adults with existing cardiovascular disease and overweight or obesity^[1]. Based on these results, in March 2024 the FDA approved Wegovy (brand-name semaglutide) to reduce the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight^[4]. The indication does not extend to compounded products or to other doses.

What the SELECT trial actually found

The SELECT trial enrolled 17,604 adults^[1]. All participants were 45 or older, had pre-existing cardiovascular disease (prior heart attack, stroke, or peripheral arterial disease), had a BMI of 27 or higher, and did not have diabetes. They were randomized to receive either semaglutide 2.4 mg weekly or placebo, alongside standard cardiovascular care.

The primary outcome measured was major adverse cardiovascular events, or MACE: cardiovascular death, nonfatal heart attack, or nonfatal stroke. Over a mean follow-up of about 40 months, MACE occurred in 6.5% of people taking semaglutide and 8.0% of people taking placebo^[1]. That is a 20% lower relative risk (hazard ratio 0.80, 95% confidence interval 0.72 to 0.90), or an absolute difference of 1.5 percentage points.

Side effects mattered too. Adverse events led 16.6% of the semaglutide group to stop the study drug permanently, compared with 8.2% of the placebo group^[1].

This is outcomes data, not just mechanistic evidence or surrogate markers. The study ran for years and tracked real clinical events (heart attacks, strokes, and cardiovascular deaths) rather than only measures such as blood pressure or cholesterol. Results vary, and trial results describe study participants, not a prediction for any individual.

Why GLP-1 medications may protect the heart

The cardiovascular effect seen with GLP-1 medications appears to work through several possible mechanisms. Understanding them helps explain why researchers think this class of drug may lower heart risk.

Weight loss reduces cardiovascular strain. The most straightforward link is this: when you lose weight, blood pressure often drops, your lipid profile can improve (lower LDL cholesterol and triglycerides, often higher HDL), and inflammation can decrease. All of these are major drivers of cardiovascular risk. GLP-1 medications can help with weight loss, and weight loss can improve heart health.

GLP-1 receptors are expressed in the heart and blood vessels. The medication may not work only through weight loss. GLP-1 receptors are present in cardiac tissue and in the endothelium (the inner lining of blood vessels). When activated, they may reduce inflammation and improve vascular function.

Anti-inflammatory effects beyond weight loss. Research suggests that GLP-1 medications may have direct anti-inflammatory effects. Chronic low-grade inflammation is a driver of atherosclerosis (plaque buildup in arteries), so reducing inflammation may help heart health independent of weight loss alone.

Improved metabolic function reduces cardiac strain. Better insulin sensitivity and improved blood sugar control reduce the metabolic burden on your cardiovascular system.

The mechanism is likely multifactorial. Weight loss, direct receptor effects on the heart and blood vessels, anti-inflammatory effects, and improved metabolic function may all contribute to the lower event rate observed in the SELECT trial.

What this means if you have cardiovascular risk

If you have a history of heart attack, stroke, peripheral arterial disease, or other established cardiovascular disease, and you also have obesity or overweight, Wegovy (brand-name semaglutide) is FDA-approved to reduce the risk of future major cardiovascular events in that group^[4]. This is not just about weight management. It is a labeled indication for cardiovascular risk reduction.

If you do not have established cardiovascular disease but have cardiovascular risk factors (high blood pressure, high cholesterol, diabetes, family history, smoking), the SELECT results do not directly apply to you. Weight loss can still improve some of those risk factors. A licensed provider can evaluate your complete risk profile and discuss whether GLP-1 treatment is appropriate as part of your overall plan.

It is important to be clear: the prescriber should review your complete cardiovascular history before prescribing. Some people with certain cardiac conditions (uncontrolled heart failure, recent arrhythmias, unstable angina) may have different considerations and need careful evaluation before starting treatment. This is why a thorough medical evaluation is essential.

Earlier cardiovascular outcome trials in GLP-1 medications

SELECT studied people without diabetes. Earlier cardiovascular outcome trials of GLP-1 medications were done in people with type 2 diabetes.

The LEADER trial, published in 2016 in the New England Journal of Medicine, examined liraglutide (another GLP-1 agonist) in 9,340 people with type 2 diabetes and high cardiovascular risk^[2]. Over a median follow-up of 3.8 years, MACE occurred in 13.0% of the liraglutide group and 14.9% of the placebo group (hazard ratio 0.87).

SUSTAIN-6, also published in 2016, examined once-weekly semaglutide at 0.5 mg or 1.0 mg in 3,297 people with type 2 diabetes, most of whom had established cardiovascular disease, chronic kidney disease, or both^[3]. MACE occurred in 6.6% of the semaglutide group and 8.9% of the placebo group (hazard ratio 0.74, about a 26% lower relative risk). The same trial found a higher rate of diabetic retinopathy complications with semaglutide^[3].

These trials studied different drugs, doses, and populations. Several GLP-1 medications have shown fewer cardiovascular events than placebo, but results from one drug and population do not automatically carry over to another.

Important distinction: branded semaglutide versus compounded semaglutide

Here is a distinction that matters: the SELECT trial, and the other cardiovascular outcome evidence on this page, comes from studies of brand-name semaglutide (prescribed for weight management or for type 2 diabetes).

Compounded semaglutide has not been evaluated in cardiovascular outcome trials, and the cardiovascular indication applies to Wegovy only. Compounded semaglutide and tirzepatide are not FDA-approved and are not the same as brand-name products such as Wegovy. They may differ in formulation, purity, and potency. The FDA does not review compounded medications for safety, effectiveness, or quality.

This matters because if cardiovascular risk reduction is a significant factor in your decision to start GLP-1 treatment, this is a conversation to have explicitly with the provider you choose. The clinical evidence for cardiovascular benefit is specific to the brand-name product at the dose studied.

Tirzepatide and cardiovascular outcomes

Tirzepatide is a newer GLP-1/GIP receptor agonist used for weight management. The cardiovascular outcome evidence for tirzepatide in people with obesity is not yet as mature as for semaglutide.

The SURMOUNT-1 and SURMOUNT-2 trials for tirzepatide studied weight loss and metabolic measures. A cardiovascular outcome trial in adults with obesity, SURMOUNT-MMO, was still running as of October 2026, with completion estimated for October 2027^[5]. Until it reports, outcome data like SELECT’s is not available for tirzepatide in this population.

If cardiovascular risk reduction is a primary goal of your treatment, a provider may weigh the fact that the outcome evidence in people with obesity is more complete for semaglutide at this time. That does not mean tirzepatide is less effective overall.

What cardiovascular benefit does not mean

GLP-1 medications are not a replacement for other cardiovascular medications or lifestyle changes. If you have high blood pressure, high cholesterol, or other cardiovascular risk factors, you still need appropriate treatment for those conditions. Blood pressure medications, statins, and other evidence-based cardiovascular therapies your provider recommends remain important.

GLP-1 medications are an addition to your overall cardiovascular risk management plan, not a substitute for it. The provider you choose should consider your complete medication list and overall plan.

Also: the SELECT results come from following people for an average of about 40 months. A relative risk reduction measured over years of follow-up does not tell you what will happen in the first few months, or to any one person.

How the process should work

At most telehealth programs, a licensed provider reviews your health history and current medications and decides whether a prescription is appropriate. If you have cardiovascular disease, that review should be thorough. Before you choose a program, ask:

• Will the prescriber review your full cardiac history? That includes prior heart attacks, strokes, stents or bypass, heart failure, arrhythmias, and your current medication list.
• Will they coordinate with your cardiologist or primary care provider? Ask whether they want recent records, lab results, or an ECG, and how they share their notes.
• Which medication and dose would they consider, and why? Only Wegovy carries an FDA indication for cardiovascular risk reduction. Ask whether the program offers brand-name or compounded medication.
• How are dose increases and side effects handled? Ask how often the prescriber checks in during escalation and who you contact if you have symptoms.

If you have chest pain, shortness of breath, fainting, or other urgent symptoms, call 911 or seek emergency care rather than waiting for a telehealth visit.

What to check before using semaglutide or tirzepatide

Programs differ in what they prescribe and what they charge. A few things to confirm:

• Brand-name or compounded? Compounded semaglutide and tirzepatide are not FDA-approved. The FDA does not review them for safety, effectiveness, or quality, and they are not the same as brand-name products such as Wegovy. They may differ in formulation, purity, and potency.
• Does the cardiovascular evidence apply? The SELECT results and the cardiovascular indication apply to Wegovy (brand-name semaglutide) at the doses on its label. They do not extend to compounded products.
• What is the total cost? Prices vary by program and dose. Compare the total cost: medication, dose increases, visits, labs, shipping, membership fees, and cancellation terms.
• Who manages your heart care? A GLP-1 prescriber is not a replacement for your cardiologist or primary care provider.

Transformation Health does not accept payment from providers. How we make money.

How to get started

If you want background before talking with a provider, see GLP-1 Medications Without Type 2 Diabetes and GLP-1 eligibility criteria.

For a detailed comparison of semaglutide and tirzepatide, including cardiovascular considerations, see Semaglutide vs Tirzepatide.

Citations

[1] Lincoff AM et al. “Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.” New England Journal of Medicine. 2023;389(24):2221-2232. https://pubmed.ncbi.nlm.nih.gov/37952131/

[2] Marso SP et al. “Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes.” New England Journal of Medicine. 2016;375(4):311-322. https://pubmed.ncbi.nlm.nih.gov/27295427/

[3] Marso SP et al. “Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.” New England Journal of Medicine. 2016;375(19):1834-1844. https://pubmed.ncbi.nlm.nih.gov/27633186/

[4] Novo Nordisk. Wegovy (semaglutide) prescribing information. US Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215256s025lbl.pdf

[5] ClinicalTrials.gov. “A Study of Tirzepatide (LY3298176) on the Reduction on Morbidity and Mortality in Adults With Obesity (SURMOUNT-MMO).” NCT05556512. Status: active, not recruiting; estimated completion October 2027 (accessed October 16, 2026). https://clinicaltrials.gov/study/NCT05556512