At a diabetes conference in Milan, researchers have quietly challenged the boundary lines drawn around one of medicine's most discussed drug classes. A large Danish-British analysis suggests that millions of people deemed ineligible for GLP-1 medications — not because they are healthy, but because their body mass index falls just below an arbitrary threshold — carry the same cardiovascular burden as those already approved to receive them. The question being raised is not merely clinical; it is a question about who gets protected, and why.
Study argues for expanding GLP-1 drug access to lower-BMI patients with heart disease risk
They had a similar risk of coronary heart disease as those already eligible
Mark
So the study is saying that roughly half of people with a BMI between 25 and 27 have the same heart disease risk as people who can already get these drugs. Why aren't they on them now?
Mimi
Because the current approval rules don't include them. The drugs are approved for BMI 30 and up, or 27 and up if you have other conditions. A BMI of 25 to 27 is technically overweight, but it falls outside the boundary. The researchers found that about half of people in that range have elevated cholesterol or inflammation—markers that put them at real cardiovascular risk.
Luke
But here's the thing: this is observational data. They're showing that people with those risk markers have similar heart disease rates to eligible patients. That's not the same as showing that giving them the drug would prevent disease. You need a trial for that.
Mimi
Exactly. That's why they're calling for clinical trials. The study makes the case that these people should be studied, not that they should automatically be prescribed the drugs.
Mark
How many people are we talking about?
Mimi
The analysis looked at over 313,000 people across two studies. About a third of them didn't qualify for the drugs under current rules. More than 90 percent of those ineligible people had a BMI in the 25 to 27 range. So we're potentially talking about millions of people globally.
Luke
One thing to note: this is a Danish and UK analysis. The risk profiles, the healthcare systems, the populations—they're specific to those countries. You can't just assume the same pattern holds everywhere.
Mark
What would expanding access actually mean for patients?
Mimi
It would mean people with a BMI just under 27 who also have high cholesterol or inflammation could potentially get a prescription for semaglutide or tirzepatide to reduce their heart disease risk, not just their weight.
Luke
And we don't yet know if that would work. That's the honest answer. The study shows the risk is there. Whether the drug prevents the disease in this group—that's still an open question.
The Pulse
- Nearly half of overweight people with a BMI between 25 and 26.9 are locked out of GLP-1 drugs despite carrying elevated cholesterol or inflammation markers that signal serious heart disease risk.
- A study of over 313,000 participants tracked for up to 18 years found that these excluded individuals were 41–47% more likely to develop cardiovascular disease — a risk profile nearly identical to those already eligible for the drugs.
- GLP-1 medications like semaglutide and tirzepatide are already known to reduce cholesterol, inflammation, heart attacks, and strokes, making the eligibility gap feel increasingly difficult to justify.
- Researchers are not yet calling for immediate prescription changes — they are calling for clinical trials to confirm that treatment would actually prevent harm in this intermediate-risk group before guidelines shift.
At a diabetes conference in Milan, researchers have quietly challenged the boundary lines drawn around one of medicine's most discussed drug classes. A large Danish-British analysis suggests that millions of people deemed ineligible for GLP-1 medications — not because they are healthy, but because their body mass index falls just below an arbitrary threshold — carry the same cardiovascular burden as those already approved to receive them. The question being raised is not merely clinical; it is a question about who gets protected, and why.
At this week's European Association for the Study of Diabetes conference in Milan, a research team from Copenhagen University Hospital presented a challenge to the current rules governing who can access GLP-1 drugs. Semaglutide and tirzepatide are approved for adults with a BMI of 30 or higher, or 27 or higher if a weight-related condition is present. But people with a BMI between 25 and 26.9 — overweight, but below the cutoff — are excluded entirely, even when their cardiovascular risk tells a different story.
Dr. Karen Hvid and her colleagues analyzed data from more than 313,000 participants across the UK Biobank and the Copenhagen General Population Study. Starting free of heart disease and diabetes, these individuals were followed for up to 18 years. Nearly 23,000 eventually developed coronary heart disease. About a third of the full group did not qualify for GLP-1 drugs under current rules, and over 90 percent of those ineligible people fell into the BMI 25–26.9 range.
What the team found was striking: between 44 and 48 percent of those excluded individuals had elevated remnant cholesterol, chronic low-grade inflammation, or both — conditions independently linked to heart disease. When outcomes were compared, this excluded group faced a 41 to 47 percent higher risk of cardiovascular disease relative to low-risk individuals. The currently eligible group showed a 35 to 41 percent increased risk by the same measure. The risk profiles, in other words, were nearly indistinguishable.
Hvid's team stopped short of recommending immediate policy change. Their findings establish that the risk is there; they do not yet prove that prescribing these drugs to this group would prevent harm. What they are calling for is the clinical trial evidence needed to answer that question — and, if the answer is affirmative, to bring millions more people within reach of medications that could meaningfully alter their health trajectories.
Researchers presenting findings this week at the European Association for the Study of Diabetes conference in Milan are making a straightforward argument: millions of people who are currently ineligible for GLP-1 drugs should be able to access them to protect their hearts.
The two medications in question—semaglutide and tirzepatide—are already approved for weight loss in adults whose body mass index reaches 30 or higher, or 27 or higher if they have at least one weight-related condition like high blood pressure, abnormal cholesterol levels, type 2 diabetes, or a history of heart disease. But there is a gap in the current rules. People with a BMI between 25 and 26.9—technically overweight but below the threshold—are locked out, even if they carry significant cardiovascular risk.
Dr. Karen Hvid of Copenhagen University Hospital and her team analyzed data from over 313,000 people tracked through two major studies: the UK Biobank and the Copenhagen General Population Study. The participants, with a median age of 58 and roughly half female, started out free of heart disease and diabetes. Over more than a decade of follow-up—stretching to 18 years in one study and 15 in the other—nearly 23,000 of them developed coronary heart disease. Some had heart attacks. Others underwent procedures to open blocked arteries or died from cardiovascular causes.
About two-thirds of the study population qualified for GLP-1 drugs under existing rules. The remaining third did not, and more than 90 percent of those ineligible people fell into the BMI 25 to 26.9 range. Here is where the analysis becomes consequential: roughly half of that excluded group—between 44 and 48 percent depending on which study—had either elevated remnant cholesterol (the cholesterol particles that are neither HDL nor LDL) or signs of chronic low-grade inflammation. Both conditions are known to increase heart disease risk.
When Hvid's team compared outcomes, they found something striking. People in the excluded BMI range who had high remnant cholesterol and inflammation faced nearly identical heart disease risk as people who were already eligible for the drugs. In one study, those excluded people with both risk factors were 41 percent more likely to develop cardiovascular disease than those without the indication and with healthy cholesterol and inflammation levels. In the other study, the figure was 47 percent. For comparison, people who were currently eligible for the drugs showed a 35 to 41 percent increased risk in the same comparison.
Hvid noted that GLP-1 drugs are known to lower cholesterol and inflammation while reducing the likelihood of heart attacks and strokes. The logical conclusion from her team's work is that the people currently left out—those with a BMI in the 25 to 26.9 range who also have elevated cholesterol or inflammation—should be candidates for treatment. They carry the same cardiovascular burden as those already approved to receive it.
But the research stops short of a prescription. Hvid and her colleagues are calling for clinical trials to test whether actually giving these drugs to the intermediate-risk group would prevent heart disease in practice. The current analysis shows the risk profile matches; it does not yet prove that treatment would help. That evidence, they argue, is the necessary next step before guidelines change and millions more people gain access to medications that could alter their health trajectories.
Notable Quotes
We found that about half of people with a BMI of 25–26.9 had levels of cholesterol and/or inflammation that increased their risk of heart problems. They had a similar risk of coronary heart disease as those who were eligible for GLP-1 RAs for weight loss—but, as things stand, they would not be prescribed them.— Dr. Karen Hvid, Copenhagen University Hospital
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