GLP-1 drugs as cardiometabolic medicines

A August 2026 editorial in the Journal of the American College of Cardiology argues that semaglutide, tirzepatide, and the broader GLP-1 receptor agonist class have been mislabelled by the media and the market as weight-loss drugs. The paper, by Harlan M. Krumholz of Yale School of Medicine, makes the case that these medicines should instead be classified as cardiometabolic health drugs whose benefits extend well beyond the number on a scale^[1].

The argument is timely. Cardiovascular outcomes data has been accumulating for nearly a decade, and it now tells a story that obesity trial headlines tend to crowd out. LEADER, SUSTAIN-6, and SURPASS-CVOT between them enrolled more than 26,000 patients and followed them for years. The data is not preliminary. The question is whether the medical and policy communities are acting on it.

What the cardiovascular trials show

The first hard cardiovascular outcomes data for a GLP-1 receptor agonist came from the LEADER trial in 2016. In 9,340 patients with type-2 diabetes and high cardiovascular risk, liraglutide produced a composite primary endpoint (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in 13.0% of participants versus 14.9% on placebo, a hazard ratio of 0.87^[2]. Cardiovascular mortality alone fell from 6.0% to 4.7%.

SUSTAIN-6, also published in 2016, studied semaglutide in 3,297 patients with type-2 diabetes. The primary composite endpoint occurred in 6.6% of the semaglutide group versus 8.9% on placebo, a hazard ratio of 0.74^[3]. Non-fatal stroke was more than halved (1.6% versus 2.7%), the most striking subcomponent finding in the trial.

The most recent data point is SURPASS-CVOT, published in December 2025 in the New England Journal of Medicine. The trial enrolled 13,299 patients with type-2 diabetes and atherosclerotic cardiovascular disease, comparing tirzepatide directly against dulaglutide rather than placebo. Tirzepatide met noninferiority for the primary MACE endpoint (cardiovascular death, myocardial infarction, or stroke): 12.2% versus 13.1%, hazard ratio 0.92^[4]. Because dulaglutide itself carries cardiovascular benefit, achieving noninferiority in this active-comparator design is a meaningful result.

Why the weight-loss framing crowds out the cardiac story

The answer is partly commercial and partly media. Phase 3 obesity trials generate striking percentage-body-weight figures that are easy to headline. Cardiovascular outcomes trials are longer, quieter events measured in hazard ratios and confidence intervals, which require more context to explain.

The Krumholz editorial argues this framing has real consequences. When a medicine is sold primarily on weight loss, coverage decisions, prescribing thresholds, and patient expectations all centre on the scale. Patients who lose less weight than average may stop treatment early, missing the cardiovascular benefit. Payers who categorise these drugs as aesthetic or lifestyle products may restrict access, denying the cardiac risk reduction to the patients who need it most.

The editorial also touches on weight stigma. Framing these medicines as treatments for the appearance of obesity implicitly frames the underlying condition as one of personal failing rather than metabolic disease. Shifting the conversation to cardiometabolic health changes the clinical register and may reduce the stigma that causes some high-risk patients to decline treatment.

What the reframing changes in practice

For patients who already have established cardiovascular disease or who carry high ten-year cardiovascular risk, the evidence supports discussing these medicines in the context of heart and metabolic health rather than appearance. The same trial data that drove regulatory approvals for obesity, in the case of semaglutide and tirzepatide, underpins a cardiovascular argument that has been in the literature for years.

The Krumholz piece does not argue that weight loss is irrelevant. It argues that weight loss is one mechanism among several, and that framing GLP-1 drugs exclusively through that lens sells the class short and may harm patients through under-prescribing and under-coverage.

What the evidence does not yet settle

Causality between the observed cardiovascular benefit and any specific mechanism (weight reduction, blood pressure lowering, direct cardiac effects via GLP-1 receptors in myocardial tissue, anti-inflammatory action) has not been established. Most CVOT participants had established diabetes; the cardiovascular benefit in patients without diabetes and without established cardiovascular disease is less characterised. Durability beyond the trial periods, which ran to roughly three to four years in the larger studies, is also an open question.

The head-to-head cardiovascular question between semaglutide and tirzepatide has not been answered in a prospective trial. SURPASS-CVOT used dulaglutide as the comparator rather than semaglutide, so the relative cardiovascular profile of the two leading agents remains inferential. That trial, if it is ever run, would be the most informative data point the field does not yet have.

If you are considering one of these medicines, the cardiometabolic framing is worth raising with your prescriber, particularly if you have a history of cardiovascular disease or a high risk score. The per-country access picture, which varies widely, is covered on our tirzepatide regulation pages.