Since pharmaceutical company Novo Nordisk realized that GLP-1 drugs are useful for diabetes, doctors and researchers have struggled to answer a seemingly simple question: Who should accept them? These drugs are very effective in inducing weight loss, and most Americans are overweight or obese. But GLP-1s are also expensive, not covered by most insurances, and are designed to pay for life, not to mention that they often cause nausea and loss of appetite. Apparently, give them to every overweight American.
Bring President Donald Trump. In his first semester, the scan showed signs of plaque accumulation in his coronary artery, which put him at risk of a heart attack. In 2020, his weight index is the threshold for obesity. This combination will make him a candidate for GLP-1 drug, and in fact, during his 2024 campaign, it is speculated that he is taking one. Then, last month, Trump's latest body showed he had lost 20 pounds, shifting him from obesity to overweight. (Trump never publicly said he was on the GLP-1 and when commented, the White House did not address the issue of how the president could lose weight. Trump is “at a peak of mental and physical condition,” White House Press Secretary Karoline Leavitt told Atlantic In an email statement. ) The most revealing aspect in the president's medical report is the list of drugs he is taking, which includes a combination that equals what doctors call "intensive lipid-reducing lipid therapy," a treatment that is usually reserved for patients at risk of heart disease. As far as the president’s health is concerned, his weight is no more important than the fact that he is using the drug regimen, and it seems to be working: his LDL ("bad" cholesterol) has dropped significantly in recent years.
Trump’s example shows that doctors and patients’ main goal should not be just changes in weight, but changes in health. GLP-1 drugs can help a wide variety of people lose weight, but for smaller Americans, their risks are likely to be justified. To say that a person’s health benefits from taking drugs are worth the money and that the gastrointestinal tract may encounter possibilities, doctors cannot rely on weight alone. Calculus can be life and death; in the United States, nearly 1,000 deaths per day are associated with diet-related illnesses. To save lives and improve health, doctors, researchers and politicians need to consider the real killer: not weight or size, but a particularly toxic fat.
When humans eat too many calories (especially too much processed, rapidly absorbing carbohydrates, so common in modern diets), fat accumulates around the waist, surrounding and invades the liver, heart, and pancreas. Doctors call it visceral, central or abdominal fat. It is more dangerous to health than fat accumulated in places like the arms and thighs, as it leaks free fatty acids and other molecules into the body, causing inflammation, boosting metabolism and causing severe damage to our organs. Visceral fat is associated with cardiovascular disease, stroke, diabetes, 13 types of cancer and possibly some forms of dementia, as well as other major chronic diseases. Reduce visceral fat and prevent these conditions and may even be treated in some cases.
Visceral fat is closely bound to two markers of metabolic disease: high insulin levels and insulin resistance. Scientists have not yet determined which one is initial, 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 insulin rises become more common (by 2018), more than 40% of Americans suffer from high insulin and therefore have chronic diseases. One in 10 Americans have at least one chronic disease, and four in 10 have more.
GLP-1 drugs are very effective in reducing visceral fat. In fact, this may be a large part of GLP-1 so improves the metabolic health of people receiving them. Therefore, the strongest case of using GLP-1 is that people with excessive visceral fat have begun to suffer from its consequences. For doctors, the key question is how to identify these people. BMI is a poor measure, but waist circumference is a good predictor of visceral fat, type 2 diabetes, and atherosclerosis. Certain abnormalities in blood lipid patterns may indicate the onset of organ dysfunction.
However, the main indicator of judging and distributing anti-obesity drugs is body weight. Initially, the FDA approved the drugs for people with a BMI of around 30 years of age, or people with a BMI of at least 27 and at least one weight-related disease. But the agency has since quietly removed references to BMI from the drug labels, which now merely states that the drugs are targeted at patients with “obese patients” or “patients who are overweight in the presence of at least one weight-related comorbidity.” Without a clear statement, this change recognizes that BMI is not a good way to body fat, nor is it the visceral fat that causes the greatest harm. However, the institution still requires clinical trials of obesity drugs to use BMI as a standard for admission to patients. When I attended obesity medicine conferences, many of the doctors I spoke with still used BMI as a guide.
Over the past decade or so, awareness among doctors and patients has increased because of the limited practicality of BMI as a health indicator. It cannot distinguish between muscle and fat. It does not explain how fat tends to be distributed differently across both men and women's bodies. These disadvantages are important when considering what patients get from GLP-1 drugs. For example, people from South Asian heritage can produce insulin resistance in BMIs with much lower BMIS. According to the American College of Cardiology, whites with a BMI of 30 can metabolize equal to South Asians with a BMI of 23.9 in terms of insulin resistance. Unfortunately, doctors don’t have an easy and reliable way to measure insulin resistance directly. Developing diagnostic tests will help determine who should be treated with anti-obesity drugs.
The United States is still deciding how to get close to GLP-1 exactly. The Trump administration has canceled a competitive business proposal to cover Medicare's D Pract Funcer, but has not ruled out future coverage. Over the past year, the FDA has expanded its eligibility guidelines for drugs and announced that these drugs are no longer lacking. This means that compound pharmacies are no longer able to produce replicas of Novo Nordisk's Wegovy and Eli Lilly's Zepbough, which will reduce the availability of cheap options, but may also curb the risks associated with imitators. Additionally, Novo Nordisk and Eli Lilly have recently launched new discount plans. Early data suggest that these drugs may help treat fatty liver disease, heart failure and possibly neurodegenerative diseases, which I suspect will lead to more people accepting them.
If GLP-1 does indeed become more common in the United States, then everyone who keeps moving forward needs to understand that they do so without endgame. GLP-1 drugs are approved on the premise that patients stay on for life, but so far, most people have taken them largely, largely due to their side effects, often at high costs and lack of insurance coverage. Scientists don’t have good data on whether and how drugs can be eliminated without gaining weight, whether they can be used safely and effectively on an intermittent basis, or how dosages can be adjusted over a long period of time. The best way to find these answers is to have the FDA ask pharmaceutical companies to collect data. It would be a serious mistake to assume that people will use these drugs forever.
All these unresolved questions will only increase the urgency of determining who is most likely to benefit from GLP-1, and who will be safer or healthier to stick to lifestyle changes and other medications. GLP-1 medicine is not a magic pill. They are a powerful tool to help control the U.S. metabolic disease crisis, and we need to correctly address it.