Is Mounjaro the weight-loss drug we’ve been waiting for?
The FDA is evaluating the new diabetes drug Mounjaro as an obesity treatment, and early results show it takes the benefits of Ozempic up a notch. Here’s how they compare.
A major barrier to addressing the epidemic of obesity has been the misconception that it is purely a consequence of behavior—a poor diet and lack of exercise.
But most physicians now recognize that obesity is a disease—a malfunction that causes a person to consume more calories than their body needs. That’s why a recent class of drugs is having far greater success in treating obesity than behavioral interventions, like dieting, ever have.
“Obesity is an inappropriate starvation response,” Ali Zentner, a weight management physician and medical director of Revolution Medical Clinic in Vancouver, Canada, said. “For whatever reason, the brain thinks it’s starving and does what it should do in the presence of famine: it’s stores energy as fat and enhances [appetite].”
That’s why some people with obesity can literally stop eating yet not lose weight right away, or lose the weight more slowly than someone without obesity. “It’s a biological and evolutionary safeguard to prevent us from dying,” she said.
For years, scientists have worked to find medications to treat this inappropriate starvation response, but most drugs have fallen short—until recently.
A new class of drugs called GLP-1 agonists, originally developed to control blood sugar in patients with type 2 diabetes, have been found highly effective for weight loss as well. Although the first such drug was approved for type 2 diabetes in 2010, these medicines have become well-known in the last decade—particularly semaglutide, which is marketed in the United States as Ozempic (for type 2 diabetes) and Wegovy (for weight loss).
The most recent arrival is Mounjaro, or tirzepatide, which takes the benefits of Ozempic/Wegovy up another notch. Though there are some important differences in how it works.
What is Mounjaro and how does it work?
Mounjaro is a once-weekly injectable medication approved by the Food and Drug Administration in May 2022 for managing blood sugar in people with type 2 diabetes. The FDA is also evaluating the drug as a treatment for obesity; a decision is expected this year.
Mounjaro works by mimicking two hormones that are secreted by the small intestine after you eat: glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), explains Zentner. [Read more about the seven hormones that affect hunger and satiety.]
Both GLP-1 and GIP boost insulin levels to clear sugar from the blood, making them effective for diabetes. But they also circulate in the brain and reduce appetite by affecting how people experience “hunger or fullness or contentment between meals, thoughts of food, and cravings for food,” explained Robert Kushner, an endocrinologist at Northwestern University’s Feinberg School of Medicine in Chicago.
Unlike semaglutide, which only mimics GLP-1, Mounjaro “is a two-for-one,” Zentner said.
Why doesn’t dieting work?
The evidence shows that behavioral interventions have a limited long-term effect for most people with obesity, Zentner said. The majority regain the weight they lose or struggle to maintain the intense calorie restriction necessary to keep the weight off.
The brain desperately wants the body to hold on to calories, so it makes more sense why people would struggle to lose weight through behavior alone, Kushner explained. “It’s very hard, behaviorally, to combat that,” he said. “These biologic forces want to keep your weight elevated.”
How does Mounjaro compare to Ozempic and Wegovy?
Ozempic/Wegovy and Mounjaro both lower the hemoglobin A1C (HbA1c) levels—a measure of a person’s average blood sugar levels over a period of about three months—in people with type 2 diabetes. Mounjaro, however, was more effective, reducing HbA1c by between 2.0 and 2.3 percent compared to semaglutide’s 1.9 percent.
The FDA application data also showed that participants lost 12 more pounds with Mounjaro than they did with semaglutide, but those trials only included people with type 2 diabetes.
Eli Lilly, Mounjaro’s manufacturer, also assessed the drug’s effects on weight loss in the SURMOUNT-1 trial, whose results made a splash at the American Diabetes Association meeting in June 2022. Participants taking the 5-milligram dose lost an average 15 percent of their body weight, the same amount seen in semaglutide trials—but effectiveness increased with dose. Those taking 10 mg lost an average 19.5 percent of their body mass, while the 15-mg dose resulted in 21 percent loss, compared to 3 percent loss in the placebo group. Patients also saw improvements in blood pressure and cholesterol levels.
What are the side effects of Mounjaro?
The most common side effects are the same gastrointestinal symptoms seen with Ozempic/ Wegovy: nausea, vomiting, diarrhea, decreased appetite, constipation, and upper abdominal discomfort or cramping.
“When you give a gut hormone in pharmacologic doses, it probably puts the gastrointestinal system into overdrive,” Kushner said. These effects often occur when patients begin taking the drug and diminish as their body becomes used to it. In the clinical trial, 3 to 7 percent of participants dropped out because of these side effects.
More serious but much rarer possible side effects include an inflammation of the pancreas, kidney failure from dehydration, severe stomach problems, gallbladder problems such as jaundice, vision changes, or even hypoglycemia (low blood sugar) if someone is taking other medications that lower blood sugar.
Mounjaro, like Ozempic/ Wegovy, may increase the risk of a very rare, hereditary cancer called medullary thyroid carcinoma, though no cases occurred in any of the trials. Kushner also said people with a history of multiple endocrine neoplasia—the growth of multiple tumors on endocrine glands—should not take these drugs.
What about facial changes or hair loss?
Several articles have highlighted other consequences from using Ozempic that may occur with Mounjaro, such as facial changes and hair thinning or hair loss. However, these are common effects from any type of weight loss. People who undergo bariatric surgery or lose weight through behavioral change also commonly experience hair loss or see their face grow gaunt or sag.
What are the long-term effects of taking Mounjaro?
The drug has not been available long enough to collect long-term data and address this question, Kushner said. But one concern with any type of substantial weight loss is the disappearance of muscle mass.
“If you lose weight, you never just lose fat,” Kushner said. You also lose muscle, “and it’s very hard to gain back muscle mass once you’ve lost it, particularly as you age,” Kushner said. People taking Mounjaro—or losing a lot of weight for any reason—should therefore “take up a robust physically active program with both aerobic and resistance training,” he said.
Zentner added that we lack long-term data on many other drugs as well, so doctors who are prescribing these medications must weigh their unknown long-term risks against the known long-term risks of obesity—which include type 2 diabetes, heart disease, and cancer. So far, the data we do have “is incredibly reassuring,” she said.
How much does Mounjaro cost?
Like Ozempic/Wegovy, Mounjaro is not cheap. Current U.S. prices run a little over $1,000 per month’s supply if not covered by insurance.
The high prices of semaglutide have led many Americans to purchase it from Canadian pharmacies if they do not have an insurance plan that will cover the drug. Health Canada approved Mounjaro in November 2022 for treatment of type 2 diabetes, but it is not yet commercially available there and has not been approved for obesity.
What happens if you stop taking Mounjaro?
Early data from semaglutide has shown that stopping the drug after substantial weight loss leads most people to regain weight, sometimes up to two thirds of what they lost. It’s likely the same would occur with Mounjaro.
“Your appetite starts to re-emerge … the portion control you had doesn’t feel enough anymore, and you basically start to think about food again,” Kushner said. “All the benefits of the drug disappear, and it’s very hard to combat the [return] of appetite because it’s a naturally occurring need.”
The fact that patients might only maintain their weight loss while continuing the medication has been a criticism of these drugs, but Zentner said that criticism arises from a misconception about weight loss.
These obesity medications “are still viewed as a ‘training camp’ for teaching you how to eat, which is not how they work,” Zentner said. Just as people with chronic conditions, such as depression or diabetes, need to keep taking a medication to keep their symptoms at bay, so do people who have obesity.
Obesity results from a complex interaction of biology and genetics, Zentner said, and these “medications are a compensation for what the body’s not doing in the first place, not an education for the body. If it’s not a behavior, then there’s nothing to learn.”
