Earlier this summer, Forrest Smith got some promising news. The Denver-based petroleum engineer, who works for the National Park Service, had read reports on a new diabetes medication called tirzepatide. Clinical trials had confirmed a potent side effect: Tirzepatide users could shed up to 20 percent of their body weight. Smith told me he spent his childhood cast as “the fat kid in school,” and his adulthood locked in a cycle of losing pounds and regaining them. Though he is not diabetic, he was aware that some doctors were prescribing the drug for weight loss and, feeling like he had nothing to lose, sought one out for treatment. He took his first weekly injection in July, and says it was like “a switch was flipped overnight.” Food cravings disappeared. When watching skinny friends eat, he used to wonder, “How do you not eat that entire plate of cookies in front of you?” That all changed. “One cookie? Totally doable.”
He now weighs 236 pounds, 24 pounds down from when he began the medication. Smith’s spouse and parents were so impressed with his progress that they decided to seek out tirzepatide, too. His young children have noticed that running around their garden now tires them out before their father. Since his first shot, Smith has been reaching deeper into his closet for clothes that will fit. “Hopefully,” he said, “I don't find parachute pants—I don’t have to go that far back.”
Tirzepatide (marketed by Eli Lilly and Company as Mounjaro) first became available to the American public in May of 2022, when it was approved by the United States Food and Drug Administration (FDA) as a diabetes treatment. And while FDA approval for using the drug specifically for weight loss appears imminent, doctors have the authority to deviate from FDA mandates when prescribing drugs, and some have been writing scripts to treat obesity at their own discretion. “I’ve been very excited about these medicines,” said Dr. Melanie Jay, director of NYU Langone’s Comprehensive Program on Obesity. “[Obesity] has always been something that's under-treated.” It might be the trickle that precedes a torrent—tirzepatide is just one in a class of new extremely effective weight loss drugs that threaten to upend the way we think about and treat obesity.
That class of drugs is called incretins. Initially created to spur insulin production in diabetic patients, incretins often left participants in drug trials with two notable side effects: satiety and delayed gastric emptying. In other words, recipients feel full quicker, while food itself moves from stomach to intestine more slowly, which makes you feel even more full. The combination of those effects caused patients to eat less and consistently lose weight.
To understand why these drugs could be so revolutionary, you need to understand how obesity works—which is often different from the way it’s talked about. Many people are under the misconception that their weight can be completely controlled by diet and exercise. (Look no further than the 18 seasons of The Biggest Loser for evidence.) But researchers and doctors are more inclined to think of the condition as just that: a chronic health condition. “Our brains regulate our appetite, and they regulate our metabolism,” said Jay. For the obese, those regulations are set to retain weight. A healthy lifestyle can help prevent obesity, but when a person who’s already overweight goes on a diet, their bodies increase appetite and decrease metabolism. The weight returns. (Exercise doesn’t seem to matter much at all.) These patients—a huge proportion of Americans—often aren’t well-served by the medical establishment. And as Matt Yglesias recently pointed out for Grid, the body-positivity movement has advocated for people to seek health at any size—an understandable reaction, but one that can obscure the real health costs of obesity.
The effective treatment options for obesity that already exist are under-used. Bariatric surgery, for example, can be an effective way to address extra weight. But surgery is seen as a drastic option, and Americans tend to think poorly of weight loss surgery. Without a comorbidity like diabetes, a prospective candidate typically needs a BMI of at least 40 to undergo the surgery—and only a small sliver of those who qualify get the procedure. That’s one reason why obesity experts see so much promise in the new drugs.
But there are big hurdles to widespread adoption, and not just questions of cost and approval that every drug faces on its way to the public. Weight loss drugs have a checkered past. “If you look back in the history of obesity, drugs that have been approved have then been taken off the market,” says Dr. Spencer Nadolsky, a physician who runs the obesity program for telehealth provider Weekend Health. Dangerous amphetamines were used as appetite suppressants, and more recent drugs, like Fen-Phen, a weight loss drug widely used in the 1990s, caused heart problems, leading to an FDA ban. Safer weight loss drugs began to reappear in the 2000s, but their efficacy was often mild.
Incretins, on the other hand, are only continuing to get more effective. The newest of these medications cause around 20 percent weight loss, within the same range that bariatric surgery achieves. And while common side effects include nausea and other gastrointestinal distress, it's a much less disruptive medical intervention than surgery.
One obesity expert at Harvard Medical School, Dr. Fatima Stanford, told me that some patients have reacted so strongly to one incretin, semaglutide, that they’ve avoided surgery completely. “They went from severe obesity with diabetes to no diabetes and no severe obesity—into a healthy weight range,” she said. “It’s effortless for them—we’re changing the way their brains see weight.” This has major quality of life implications. “When you have higher levels of obesity,” said Jay, “losing 15 or 20% of your body weight is huge, right? It's huge for resolving comorbidities and preventing diabetes, and all sorts of things.”
One Washington woman in her 50s named Suzy, who asked to only be identified by her first name, has lost 26 pounds since starting tirzepitide. She has three siblings and two parents with type two diabetes. With the drug, she thinks she can avoid that disease. Another woman, Rachel McLaughlin, who started an oral incretin in 2021, said weight loss gave her the confidence to join an art class. “I don’t look like I’m carrying the weight of the world around,” she said.
But remarkable advances in medical technology don’t mean much if they’re impossible to access. McLaughlin faced that setback when she lost her job earlier this year. Losing health insurance increased the cost of her prescription from $25 (£22) to more than $2,000 (£1,772) per month. Off the medication, she regained 15 of the 25 pounds she’d lost. Progress only resumed once she found a new job in June that restored her coverage.
Like other diabetes medications, incretins are meant to be taken indefinitely. Dr. Mike Albert, co-founder of Accomplish Health, a telehealth company specializing in obesity, said the biggest influences over what he prescribes are cost and coverage. “That’s the limiter,” he said. “If a medicine is not covered on a health plan, or under the benefits of a health plan, or if it is cost prohibitive, it doesn't matter how good I think it will do for this person.”
Medicare, which heavily influences how private insurance charts its own plans, doesn’t cover anti-obesity medications. (In an unfortunate twist, Medicare’s policy on obesity meds came in partial response to the Fen-Phen scandal.) A bill sitting in Congress called the Treat and Reduce Obesity Act would change that, but its fate remains unclear.
Changing how both the public and health care system views obesity won't happen overnight—after all, it was only in 2013 that the American Medical Association acknowledged obesity as a chronic illness.
“Most primary care doctors, unfortunately, still suffer from an obesity stigma and bias,” said Nadolsky. If you cornered a doctor at a dinner party, Stanford said, they’d likely be able to tell you how to treat an esoteric condition like Behcet’s disease. “Then if you ask them about obesity, which affects almost half the population, they would look like, I don't know what to do.”
This all means that widespread adoption of incretins for weight loss still faces significant barriers. There is also the thorny (and still mostly theoretical) question of whether these drugs are appropriate for people who simply want to lose a few pounds. But for patients currently experiencing obesity and metabolic dysfunction, the possibilities a prescription brings are already too great to ignore. Suzy told me that she and her husband are planning to travel through Europe in retirement—unthinkable until she began a tirzepatide regimen. McLaughlin has travel plans too, but she's focusing on the beginning of the trip. “I cannot wait to get on a plane,” she said, “and take a seat comfortably.”
