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Mounjaro leads to far more weight loss than Ozempic, study finds: What to know about side effects, safety

Tirzepatide, which is sold under the brand name Mounjaro for Type 2 diabetes, has also received FDA approval as the weight-loss medication Zepbound.
/ Source: TODAY

Ozempic has become a blockbuster drug thanks to its ability to help people lose weight, but Mounjaro, another Type 2 diabetes treatment, appears to be far more effective for weight loss, a new analysis suggests.

The study, which hasn't been peer reviewed yet, found people taking tirzepatide — the active ingredient in Mounjaro — were up to three times more likely to achieve weight loss than those using semaglutide, the active ingredient in Ozempic and its sister drug, Wegovy.

The findings are based on real-world data from more than 18,000 U.S. adults who had obesity or were overweight and started using Ozempic or Mounjaro between May 2022 and September 2023.

Patients taking Mounjaro were three times more likely to lose 15% of their body weight and over two and a half times more likely to lose 10% of their body weight than those taking Ozempic or Wegovy, the analysis found.

They also experienced larger reductions in weight at three, six and 12 months into treatment.

Separate research, released in October 2023, also found tirzepatide may be more effective for weight loss plus blood sugar control than semaglutide.

Here's what to know about the diabetes drug Mounjaro:

What is Mounjaro?

Mounjaro, also known by its active ingredient, tirzepatide, is a prescription medication approved by the FDA to treat Type 2 diabetes. It is given as a once-weekly injection under the skin to help control blood sugar.

Tirzepatide was approved for weight loss by the FDA under the brand name Zepbound in November 2023.

It works by targeting the receptors in the brain for two different hormones, GIP and GLP-1, which the body produces after eating. Activating these receptors can decrease appetite and food intake, as well as help the body manage its insulin production.

Semaglutide only targets one hormone, "so you're essentially getting more bang for the buck when you take Mounjaro," NBC news medical contributor Dr. Natalie Azar said in a Nov. 28 segment on TODAY.

Studies have found there’s a “synergistic action” when the body’s receptors for both GIP and GLP-1 are activated, leading to greater weight loss. Some research indicates Mounjaro's results could be similar to those of gastric bypass surgery, Azar noted in 2022 after a study found the drug led to substantial weight loss.

“We need this tool in the toolbox,” Azar said. “It’s so important and so relevant. The majority of Americans are either overweight or obese.”

Weight loss can be hard for people with diabetes because of the way their body responds to insulin, so tirzepatide could be “extremely helpful” for patients with Type 2 diabetes who need to slim down, Dr. Shauna Levy, medical director of the Tulane Bariatric Center in New Orleans, told NBC News.

So, will Mounjaro make people forget about Ozempic or Wegovy?

“I don’t think so,” Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine and NewYork-Presbyterian, tells TODAY.com. He’s a scientific adviser for Eli Lilly and Novo Nordisk, which makes Ozempic and Wegovy.

“Having more medications that are slightly different is a good thing because some people may respond better to one and some may respond better to another," he adds.

Mounjaro for weight loss: What the research says

An analysis, presented in October 2023 at the annual meeting of the European Association for the Study of Diabetes in Hamburg, Germany, found that Mounjaro may be more effective than Ozempic for weight loss and blood sugar management. The research hasn't been submitted to a medical journal for publication yet, according to a news release announcing the results.

Researchers analyzed 22 randomized controlled trials that involved 18,472 patients with Type 2 diabetes. (Only two of the studies compared tirzepatide and semaglutide directly; the other 20 were used to produce "indirect comparisons," per the press release.)

All of the patients self-injected with either a 5-, 10- or 15-milligram dose of tirzepatide once a week or a 0.5-, 1- or 2-milligram dose of semaglutide once a week for at least 12 weeks. 

Each of the three tirzepatide doses reduced A1C — a measure of blood sugar — more than the respective low-, medium- and high-dose of semaglutide, the analysis found.

For weight loss, tirzepatide was also "superior" to semaglutide, especially at higher doses, the statement noted. Patients who took the highest dose of Mounjaro lost almost 13 pounds more, on average, than patients who took the highest dose of Ozempic.

Mounjaro previously showed striking results in two clinical trials.

The medication helped obese or overweight people with Type 2 diabetes lose up to 15% of their body weight, or 34 pounds, drug maker Eli Lilly announced on April 27, 2023.

That compares to a 3% weight loss, or 7 pounds on average, for patients taking a placebo, according to the trial results. The study followed more than 900 adults who were randomly assigned to get either a placebo or one of two dose strengths of tirzepatide for 17 months.

Another trial found tirzepatide helped overweight or obese patients without diabetes lose up to almost a quarter of their body weight, or 22%, after 17 months compared to a 2% weight loss with a placebo.

In comparison, Wegovy, the version of Ozempic approved for weight loss by the FDA, helped patients lose an average of 12% of their initial body weight after 16 months compared to those who received placebo.

When asked if patients have to keep taking the drug to maintain weight loss, Eli Lilly said an upcoming trial will evaluate the efficacy and safety of tirzepatide for maintenance of weight loss in overweight or obese adults.

How does Mounjaro work for weight loss?

Mounjaro, which has tirzepatide as its active ingredient, works in a similar way to semaglutide, the active ingredient in Ozempic and Wegovy. They’re all in a class of drugs called GLP-1 agonists and mimic the effects of a hormone the body releases when people eat food. Patients have reduced appetite, and when they do eat, they feel full sooner.

But tirzepatide also mimics a second hormone, called GIP, which may improve how the body breaks down sugar and fat in addition to reducing appetite, NBC News reported.

Jennifer Huber of North Port, Florida, has been taking Mounjaro for almost a year to treat her Type 2 diabetes. She was surprised to lose about 60 pounds.

“It has changed my life,” Huber told NBC News. “Even though I’m a smaller person now, I feel that I’m more visible in society. It’s been a good thing.”

Mounjaro side effects

Huber said she’s had side effects such as nausea and constipation. Other common side effects of Mounjaro include diarrhea, vomiting, indigestion and stomach pain, according to Eli Lilly.

Serious side effects of the drug include pancreatitis, low blood sugar, serious allergic reactions, kidney problems, vision changes and gallbladder problems, the company noted in a news release.

The October 2023 research comparing tirzepatide and semaglutide also noted that the highest dose of tirzepatide came with the highest increased risk for nausea, vomiting and diarrhea, compared to the placebo group and those using semaglutide.

Huber is also worried she’ll gain the weight back if she stops taking Mounjaro.

Dr. Christopher McGowan, an obesity medicine specialist in Cary, North Carolina, who has prescribed Mounjaro off-label for weight loss in the past says weight recurrence is "near-universal" after patients stop using the drug.

"This is identical to what we see after cessation of Wegovy, Ozempic, or any GLP-1 medication, for that matter," McGowan tells TODAY.com.

"These medications, while potent and highly effective for the treatment of weight, must be continued indefinitely, or weight recurrence is inevitable. They are a treatment, not a cure."

What to know before considering Mounjaro

The list price of Mounjaro is about $1,023 per fill, which is equal to a month’s supply or four injector pens, according to Eli Lilly.

Wegovy has a list price of $1,349 for a month’s supply. Patients have to keep taking it for the drug to work, otherwise they will regain two-thirds of their prior weight loss, studies have shown.

Dr. Zhaoping Li, professor of medicine and chief of the division of clinical nutrition at the University of California, Los Angeles, says she doesn’t think drugs like tirzepatide or semaglutide are the solution to the obesity epidemic. Almost 42% of adults in the U.S. are obese, according to the Centers for Disease Control and Prevention.

Bariatric surgery, which leads to substantial weight loss, has been around for years and hasn’t moved the needle that much, Li points out, noting that many patients eventually gain the weight back.

People must learn healthy eating habits for long-term weight loss, she says.

“I really don’t think we can help our patients just with a prescription — giving it to them without doing the fundamentals,” Li tells TODAY.com. “It’s not realistic to think that from this point on, you can give yourself shots for the rest of your life without any problems.”Tirzepatide for weight loss was studied in the context of a reduced-calorie diet and increased physical activity, Eli Lilly said. Semaglutide is also meant to be used in addition to eating less and moving more, according to the FDA.