FDA Approves Most Potent Weight Loss Drug Yet

Weight loss drugs have dominated the headlines over the past year, and now there’s a new medication that may be the most effective one yet.

On Nov. 11, the U.S. Food and Drug Administration (FDA) approved tirzepatide (which will be sold under the brand name Zepbound), to treat overweight and obesity. Made by Eli Lilly and Co., the drug is already approved, in different doses, for type 2 diabetes, as Mounjaro, and its effectiveness in those patients is due in part to its weight loss effects.

About 70% of Americans are overweight, with a body mass index (BMI) between 27 and 30, or obese, with a BMI over 30—which increase the risk of a host of other health problems, including heart disease, diabetes, osteoarthritis and more. Yet there really haven’t been effective medications to treat obesity. Since its approval in 2021, semaglutide, made by Novo Nordisk and sold as Wegovy, has helped enough people lose a significant amount of weight to prompt more doctors to see overweight and obesity as chronic conditions, similar to high blood pressure, diabetes, and high cholesterol, all of which are treated with medications.

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Lilly submitted studies to the FDA showing that tirzepatide helped people who were overweight or obese and did not have diabetes to lose about 18% of their body weight compared to people receiving a placebo. In previous studies, those with diabetes lost about 12% of their weight on average. (In comparison, people without diabetes lost an average of 15% in semaglutide trials.)

That might not sound like that much, but it’s still more than people typically lose by changing diet and exercise alone, which generally leads to body weight drops in the single digit percentages. That’s why obesity experts say these drugs could represent a turning point in weight management.

Patients inject Zepbound once a week in progressively higher doses over up to 20 weeks to achieve the maximum dose of 15 mg. The FDA noted that the drug can cause side effects such as nausea, vomiting, hair loss, and reflux; in the animal studies, the drug was linked to thyroid tumors but it’s not clear if the same risk occurs in people, so the agency warned that people with a history of thyroid cancer should not take the medication.

Tirzepatide belongs to a group of drugs that mimics incretins, which are hormones released by the gut in response to food. Incretins signal cells in the pancreas to secrete insulin, which breaks down the glucose in food and helps to regulate glucose in the blood. Without enough incretins, blood sugar levels can escalate, contributing to weight gain, diabetes, and a number of other metabolic conditions. While scientists have known for about 50 years that the incretins perform this function, they have not been able to mimic the hormones as a treatment, because they are too short lived, says Dr. Daniel Skovronsky, chief scientific and medical officer and president of Lilly Research Laboratories, who was part of the team that developed tirzepatide. Over decades, Lilly’s scientists, along with others in the pharmaceutical industry, worked to find ways to stabilize and extend the longevity of incretins in the body. After years of experimenting with various incretins in mice, Skovronsky and his team found that combining them could improve both glucose and weight control. Tirzepatide is a combination of two of the most effective of these incretins: glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP). It’s the first dual-acting weight loss drug of its kind. (Semaglutides, including Ozempic and Wegovy, target a single incretin, GLP-1).

The combination proved to be a potent one. In the first safety study of tirzepatide, which involved a small number of patients with type 2 diabetes, the team already saw considerable weight loss. So in 2016, when the larger study was completed and showed a dramatic weight loss of about 12% to 13% of body weight among patients, he says “I wasn’t surprised, because I remember thinking, ‘this is exactly what I predicted from the animal studies.’ I was really excited to advance tirzepatide forward not just for type 2 diabetes but also for chronic weight management or obesity.”

Based on those results, the drug was eventually launched six years later in 2022, for people with type 2 diabetes, the fastest development in the company’s history. Given the drug’s dramatic effect on weight, Lilly decided to study and pursue FDA approval for overweight patients and those with obesity as well. Ultimately, the FDA did not approve the drug as a weight loss option for people who want to shed a few pounds. Doctors can prescribe the drug only for people who are overweight, with a BMI of 27 to 30, if they have at least one additional risk factor associated with their excess weight, such as high blood pressure or high cholesterol, or for anyone with a BMI of 30 or more, which is considered obese.

The market for such a drug is huge, of course, not just in the U.S. but across the world, where about half of the global population is expected to be overweight or obese in the next few decades. In a conversation with TIME weeks before the approval, Lilly’s CEO Dave Ricks said that treating obesity could also result in huge cost savings for the health care system, which is currently treating the expensive consequences of obesity—from heart disease and diabetes to kidney disease and joint issues. “Overweight and obesity is a huge drag on the cost of health care in this country, contributing over $400 billion in direct costs, and over $1 trillion in indirect costs,” he said.

Read more: Column: Ozempic Can’t Fix America’s Obesity Crisis

The FDA’s approval of tirzepatide, following the approval of semaglutide in 2021, gives doctors and patients two of the most potent drugs yet to treat weight loss. Having a growing formulary of effective weight loss drugs may help doctors, patients and, most importantly, insurance companies to recognize obesity as a chronic medical problem, rather than as a consequence of poor lifestyle choices. There’s evidence that the medication could supplement diet and exercise changes; in a Lilly study of people who were overweight or obese but did not have diabetes who took Zepbound, those who started with diet and exercise alone and lost  on average 6.9% body weight, and then added the drug lost an additional 21% body weight over 72 weeks, compared to a placebo group that on average gained back 3.3% body weight.

Doses of Zepbound should be available in coming weeks at pharmacies, company executives said during a briefing after the approval. But access may still be a challenge for some. Zepbound will cost 20% less than its main competitor Wegovy for those with insurance coverage, but both drugs remain expensive, at just over $1,000 for a month’s supply, and not all insurers cover obesity treatments. Lilly announced that those whose insurance plans do not cover anti-obesity treatments will be eligible for a 50% discount. 

Ricks said that the company is developing next-generation incretins as well, and is in late stage trials with a weight loss drug that combines three of them. Lilly’s scientists are also developing an oral form of tirzepatide that would not require injections. “It’s quite likely that obesity, like other chronic conditions, is heterogenous, and different people have different causes of their obesity,” says Skovronsky. “That’s why we need different therapies that could address different types of obesity. We’re not there yet today, but that’s the future.”