By Novid Parsi from the 不良研究所Pulse.
It’s been just over three years since the FDA first approved the diabetes drug Wegovy for chronic weight management. In that time, semaglutide (the generic name for Wegovy and Ozempic, a diabetes medicine that also can be used for weight loss) has surged in use, becoming one of the most popular prescription drugs in the United States.
And for good reason. About two in five U.S. adults have obesity (a body mass index of 30 or higher), according to the Centers for Disease Control and Prevention. Although associated with more than 200 comorbidities, such as diabetes and heart disease, obesity historically has been seen as a personal failing—when, in fact, it’s a disease that can be treated medically like any other disease.
“For decades, we’ve been telling people to eat less, move more and change their diet. And that hasn’t done enough to treat the disease of obesity because we’ve been ignoring the biology of it,” says Beverly Tchang, MD, Assistant Professor of Clinical Medicine, Weill Cornell Medicine.
The new wave of medications targets obesity’s biology. But how exactly do they work? In short: They enhance something our bodies already do.
Whenever we eat, our stomach stretches and enlarges, signaling to our brain that we’re getting full. Another biological process is at work, too: Our gut releases peptide hormones that make us feel full and tell our brain we’re no longer hungry. One of these satiation hormones is called glucagon-like peptide-1 (GLP-1). But our natural GLP-1 is rapidly degraded by enzymes in our body.
Anti-obesity medications have synthetic GLP-1 receptor agonists that substitute and mimic natural GLP-1 and are resistant to the enzymes, so they can last for a week or more. GLP-1 receptor agonists also slow down the emptying of our stomach and the movement of food throughout the GI system. As a result, we feel less hungry and don’t eat as much.
“With the disease of obesity, there is a disruption in the communication between the brain and the gut,” says Melanie Jay, MD, MS, Associate Professor, Departments of Medicine and Population Health, and Director, Comprehensive Program on Obesity, NYU Grossman School of Medicine.
In essence, weight-loss drugs reset the communication between the brain and gut. “These medications work by regulating appetite centers in the brain, so the relationship with food changes. People feel full after a normal-sized portion,” says Tchang, adding that the meds clear “the food noise in the back of their heads.”
Semaglutide drugs such as Wegovy and Ozempic are modified, longerlasting GLP-1 receptor agonists that can be injected just once a week. A similar Type 2 diabetes drug called tirzepatide, under the brand names Mounjaro and Zepbound, is semaglutide plus a GIP (glucose-dependent insulinotropic polypeptide) receptor that stimulates insulin secretion— promoting weight loss and lowering blood sugar. The FDA first approved semaglutide for weight loss in June 2021, tirzepatide in December 2023.
The drugs have proven highly effective. The longest clinical trial yet of Wegovy followed people on the drug for four years and found they experienced an average weight loss of just over 10%. Another study saw an average weight loss of 15% for people on semaglutide after 68 weeks. “Obesity is damaging in many ways, and almost everybody with obesity would benefit from weight loss, which is promoted by these medicines,” says David E. Cummings, MD, Professor of Medicine, University of Washington, and Director, Weight Management Program, VA Puget Sound Health Care System.
Weight-loss medications slow down gastric emptying and the movement of food through our digestive system, so the food we consume sits in our stomach and intestines longer. As a result, these drugs can lead to gastrointestinal side effects such as nausea, constipation or, rarely, diarrhea. Many people get at least one of these GI symptoms, though they tend to be “relatively minor,” Cummings says.
Especially when they start taking weight-loss drugs, individuals need to eat smaller meals; avoid fatty, greasy and spicy foods; and drink plenty of water. With time, most people on weight-loss drugs learn to avoid the foods that trigger GI symptoms, or their body gradually adjusts. Very few people have to quit the drugs entirely because of side effects, Cummings says.
There’s also a chance of getting gallstones, which can happen when people lose a lot of weight quickly. And the drugs can be challenging for people who fear needles, since most weight-loss drugs require weekly self-injections.
Without insurance coverage, weight-loss drugs come at a hefty price—around $1,000 to $1,300 every month. And with supply chain shortages for these sought-after drugs, access can vary widely depending on a person’s health insurance and pharmacy.
The drugs are so expensive, Cummings notes, that a patient could pay for a gastric bypass operation to promote major weight loss permanently for about the same amount it would cost for less than two years’ worth of weight-loss meds. If every U.S. adult with obesity started taking these drugs, “it would constitute an unbearable load on the healthcare system that would break our bank,” Cummings says.
The main reason patients stop taking weight-loss medication is their high cost, Cummings notes. “Cost is the biggest challenge,” Tchang echoes.
In the face of that challenge, some individuals turn to online compounded medications. A small number of these online meds are counterfeits. One problem with this route is that even if they get good meds, patients don’t get the medical support they need. Their weight loss could mean they need smaller dosages of other drugs they’re taking. Patients won’t know that, however, without a qualified healthcare provider prescribing and monitoring their intake.
If name-brand drugs such as Ozempic and Wegovy aren’t available or simply cost too much for patients, physicians can look for alternative, less expensive medications. Some oral medications, such as naltrexone/ bupropion and phentermine/topiramate, can be available from mail-order pharmacies for just about $100 per month without insurance. The diabetes drug metformin and the epilepsy drug topiramate, for instance, are widely available, comparatively low-cost generic drugs that can be used for obesity.
People on average might lose only about 2% to 10% of their weight on these alternative drugs—not as much as the 15% average on semaglutide. But those are only averages. “Some people do really well and can lose more than 10% of their weight” on alternative meds or combinations of them, Tchang says.
“The most common question I get from individuals considering these medicines is, ‘How long am I going to have to take it?’ Most feel they don’t want to be on something that’s a life sentence,” Cummings says. “But I have to tell them they’ll have to take it for the foreseeable future.”
Weight-loss drugs are not a magic pill. You don’t simply take them to hit a certain number on the scale and then never have to take them again. These are long-term, if not lifelong, medications.
American adults generally gain about half a pound to a pound of weight per year from ages 20 to 65, Cummings says. Once they reach their 80s, adults begin to lose weight naturally—but until that happens, people with obesity likely will need to stay on the weight-loss drugs.
At some point while taking the meds, individuals tend to plateau and don’t lose any more weight. But if they stop taking the drugs, they likely will regain the weight—and lose the benefits of weight loss. “When they have been on the medications and then go off them, most people will gain back much of the weight they lost in one year on average,” Jay says.
Consider the medications that people take for high blood pressure or high cholesterol. People don’t stop taking those meds once their blood pressure or cholesterol levels are under control—it’s the meds that are keeping them healthy. Similarly, weight-loss drugs don’t permanently alter a person’s biology; they work only as long as they’re taken.
“We don’t have lifelong studies for these medications, but we do have lifelong studies of obesity,” Tchang says. We know both the risks of uncontrolled obesity and the benefits of weight-loss drugs. “When they think about it in those terms, most of my patients choose to remain on the medication,” Tchang says. Jay says, “Obesity is a chronic disease, and we treat chronic diseases chronically.”
Despite the benefits of weight-loss drugs, only one in four U.S. patients prescribed Ozempic or Wegovy for weight loss still took the meds two years later, according to a 2024 study that did not look into the reasons why people quit. To be sure, medication nonadherence is a larger problem, with adherence rates for most meds for chronic conditions only in the 50% to 60% range.
But allied health professionals can make a difference in people’s experience with weight-loss meds—and can help patients stay on them. Beyond providing the drugs and needles, healthcare providers can support patients by taking three critical first steps.
- Learn what obesity is—and what it isn’t. Obesity is a disease a person has, not a choice they’ve made. “Patients with obesity meet a lot of weight stigma in the medical community,” Tchang says. “So, the first step is to educate yourself. Understand that obesity is a disease, and communicate that.” “It’s really important for allied professionals to understand that obesity is a disease and not a moral failing,” Jay says. “We often blame the patient when most causes of obesity are not the patient’s fault. Instead, it’s the interaction between their genes and their environment, including the foods they can access.”
- Take a nonjudgmental stance toward people with obesity—and to the way they want to lose weight. Jay has had some patients tell her they prefer to, or have been told they should, “lose weight the natural way or the right way”—as if there’s shame attached to taking medicine for a medical condition. Medications treat weight loss but not the stigma that people with obesity endure and often internalize.
- Inform patients about what they might experience on the meds. Communicate the potential GI side effects and how patients can manage their diets to mitigate symptoms. Also, for now, most of these drugs are self-injected once a week. Health professionals can assure patients that the needles are very short and thin. “Even people with a needle phobia usually can do it themselves and have no trouble,” Cummings says.