Ever since the pharmaceutical company Novo Nordisk realized that GLP-1 drugs were useful for more than diabetes, doctors and researchers have struggled to answer a deceptively simple question: Who should be taking them? The medications are highly effective at inducing weight loss, and most Americans are overweight or have obesity. But GLP-1s are also expensive, not covered by most insurance, and designed to be taken for life—not to mention that they frequently give rise to nausea and a loss of appetite. Giving them to every overweight American clearly isn’t appropriate.
Take President Donald Trump. During his first term, a scan showed signs of plaque buildup in his coronary arteries, which put him at risk of a heart attack. In 2020, his body mass index was just over the threshold for obesity. That combination would have made him a candidate for a GLP-1 drug, and indeed, throughout his 2024 campaign, people speculated that he was taking one. Then, last month, Trump’s latest physical showed that he had dropped 20 pounds, moving him from obese to overweight. (Trump has never publicly said that he is on a GLP-1, and when reached for comment, the White House did not address questions about how the president had lost the weight. Trump is “in peak physical and mental condition,” White House Press Secretary Karoline Leavitt told The Atlantic in an emailed statement.)The most revealing aspect of the president’s medical report was the list of drugs he is taking, which includes a combination that amounts to what doctors call “intensive lipid-lowering therapy”—a treatment usually reserved for patients who are at significant risk of cardiac disease. As far as the president’s health is concerned, his weight is no more important than the fact that he is on that drug regimen and that it seems to be working: His LDL (the “bad” cholesterol) has dropped dramatically in recent years.
Trump’s example shows that doctors’ and patients’ primary goal should not be changes in weight alone, but changes in health. GLP-1 drugs can help a wide spectrum of people lose weight, but their risks are likely justified for only a smaller subset of Americans. To say whether the health benefits a person might gain from taking the drugs are worth the expense and likely gastrointestinal distress, physicians cannot rely on weight alone. The calculus can be life-and-death; nearly 1,000 deaths a day are linked to diet-related disease in the United States. To save lives and improve health, doctors, researchers, and politicians need to reckon with the true killer: not weight or size, but a particularly toxic kind of fat.
When humans eat too many calories—especially too many of the highly processed, rapidly absorbed carbohydrates that are so common in the modern diet—fat accumulates around the waist, surrounding and invading the liver, heart, and pancreas. Doctors call it visceral, central, or abdominal fat. It’s more dangerous to health than fat that accumulates in places such as the arms and thighs because it leaks free fatty acids and other molecules into the body, generating inflammation, upending the metabolism, and wreaking havoc on our organs. Visceral fat is linked to cardiovascular disease, stroke, diabetes, 13 types of cancer, and likely some forms of dementia, among other major chronic illnesses. Reduce visceral fat, and these conditions can be prevented or even, in certain cases, treated.
Visceral fat is closely tied to two hallmarks of metabolic disease: high insulin levels and insulin resistance. Scientists haven’t yet determined which comes first, visceral fat or elevated insulin, but they know that high insulin levels are part of a vicious cycle that promotes fat storage, visceral fat, and disease. As elevated insulin has become dramatically more common—by 2018, more than 40 percent of Americans had high insulin—so too has chronic disease. Six in 10 Americans have at least one chronic disease, and four in 10 have more.
GLP-1 drugs are remarkably effective at reducing visceral fat. In fact, that may be a large part of why GLP-1s so improve the metabolic health of people who take them. The strongest case for use of GLP-1s, then, is in people with excess visceral fat who have begun to suffer its consequences. The crucial problem for physicians is how to identify those people. BMI is a poor measure, but waist size is a good predictor of visceral fat, type 2 diabetes, and atherosclerosis. Certain abnormalities in blood-lipid patterns can indicate the beginning of organ dysfunction.
And yet, the primary metric by which anti-obesity drugs are judged and distributed is weight. Originally, the FDA approved these medications for people with a BMI of 30 or above, or with a BMI of at least 27 and at least one weight-related ailment. But the agency has since quietly removed its references to BMI from the drugs’ labels, which now simply state that the medications are for patients “with obesity” or those who are “overweight in the presence of at least one weight-related comorbid condition.” Without explicitly saying so, this change recognizes that BMI is not a good measure of body fat, nor of the visceral fat that causes the most harm. Yet the agency still requires that clinical trials of obesity drugs use BMI as a criterion for enrolling patients. When I go to obesity-medicine meetings, many of the physicians I speak with still use BMI as a guideline.
Over the past decade or so, awareness has grown among doctors and patients alike that BMI has limited utility as a health metric. It doesn’t distinguish between muscle and fat. It doesn’t account for how fat tends to be distributed differently on male and female bodies. These shortcomings are important when considering what a patient has to gain from a GLP-1 drug. People of South Asian heritage, for example, can develop insulin resistance at much lower BMIs than other populations. According to the American College of Cardiology, in terms of insulin resistance, a white person with a BMI of 30 can be metabolically equivalent to a South Asian person with a BMI of 23.9. Unfortunately, doctors do not have easy and reliable ways to measure insulin resistance directly. Developing a diagnostic test would go a long way in helping determine who should be treated with anti-obesity medications.
The United States is still deciding how exactly to approach GLP-1s. The Trump administration scrapped a Biden-administration proposal to cover anti-obesity medications under Medicare’s Part D drug benefit, but it hasn’t ruled out future coverage. Within the past year, the FDA has both expanded its eligibility guidelines for the drugs and declared that the drugs are no longer in shortage. That means that compounding pharmacies can no longer produce replicas of Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, which will reduce the availability of cheaper options but might also curb the risks associated with copycats. Plus, Novo Nordisk and Eli Lilly have recently introduced new discount programs. Early data suggest that the drugs may be useful in treating fatty liver disease, heart failure, and possibly neurodegenerative diseases, which, I suspect, will lead even more people to take them.
If GLP-1s really do become more common in America, everyone who goes on them needs to understand that they are doing so without an endgame. GLP-1 drugs were approved under the premise that patients will stay on them for life, but so far, most people take them for less than a year, in large part because of their side effects, typically high cost, and lack of insurance coverage. Scientists do not have good data on whether and how to get off the drugs without regaining weight, whether they can be used safely and effectively on an intermittent basis, or how to adjust doses downward over the long term. The best way to find those answers is for the FDA to require pharmaceutical companies to gather the data. Letting the companies off the hook by assuming that people are going to be on these drugs forever would be a grave mistake.
All of these unanswered questions only add to the urgency of determining who is most likely to benefit from GLP-1s, and who would be safer or healthier by sticking with lifestyle changes and other medications. GLP-1 drugs are not a panacea. They are one powerful tool to help control America’s crisis of metabolic disease—one that we need to get right.
The post Who Should Really Be on Weight-Loss Drugs? appeared first on The Atlantic.
