The U.S. Food and Drug Administration (FDA)–approved diabetes medication Mounjaro (tirzepatide) is one step closer to approval as a treatment for adults with overweight or obesity.
In SURMOUNT-2, a second phase 3 clinical trial for chronic weight management, Mounjaro helped people with diabetes lose nearly 16 percent of their body weight (or an average of 34 pounds) over an 18-month period, according to an April 27, 2023, announcement by Eli Lilly, the manufacturer of the drug.
"Obesity is a difficult-to-manage disease, and it's even more difficult for people living with type 2 diabetes," said Jeff Emmick, MD, PhD, the senior vice president of product development at Lilly, in the statement. "The degree of mean weight reduction seen in SURMOUNT-2 has not been previously achieved in phase 3 trials for obesity or overweight and type 2 diabetes."
What We Already Know About Mounjaro
This trial looked specifically at adults with type 2 diabetes with overweight or obesity, and reinforces what’s been seen previously with tirzepatide, says Fatima Cody Stanford, MD, MPH, an associate professor of medicine at Harvard Medical School and an obesity medicine physician scientist at Massachusetts General Hospital in Boston. Dr. Stanford was not involved in this trial.
“These findings aren’t surprising, since we’ve seen really great results with this drug in patients with type 2 diabetes,” says Dr. Stanford.
Mounjaro was first approved in May 2022. It belongs to the same class of drugs — glucagon-like peptide-1 (GLP-1) agonists — as another FDA-approved weight loss drug called semaglutide (Wegovy). Semaglutide is sold under the brand name Ozempic when prescribed for type 2 diabetes.
Both tirzepatide and semaglutide are delivered via self-injection under the skin of the stomach, thigh, or upper arm once per week.
In the first phase 3 trial that looked at the efficacy and safety of Mounjaro in people with overweight or obesity who did not have diabetes, SURMOUNT-1, Stanford says, the weight loss findings were very impressive. In that trial, people shed even more pounds — up to 22.5 percent of their body weight.
The average total weight loss was higher in the earlier trial in people without T2D, which is to be expected, says Stanford. “We see this consistently. Although metabolic or bariatric surgery and pharmacotherapy are effective in people with diabetes, they typically don’t respond as well as people without diabetes,” she says.
Mounjaro’s Weight Loss Results Are ‘Game Changing’
A total of 938 adult participants with obesity or overweight and type 2 diabetes participated in the trial. Along with a reduced-calorie diet and increased physical activity, people took either 10 milligrams (mg) or 15 mg of Mounjaro versus placebo.
Study participants had a mean baseline body weight of 222 pounds (lb) and a baseline A1C of 8.0 percent.
Participants taking tirzepatide achieved average weight reductions of 13.4 percent (29.8 lb or 13.5 kilograms [kg]) on 10 mg and 15.7 percent (34.4 lb or 15.6 kg) on 15 mg compared with placebo.
More than 80 percent of participants on either dose lost 5 percent or more of their body weight.
Reductions in A1C compared with placebo were similar to what was found in the clinical trials for the drug's use as a type 2 diabetes treatment.
Newest Trial Results Solidify the Efficacy of Tirzepatide for Overweight and Obesity
These findings demonstrated weight loss similar to what was observed in earlier trials of Mounjaro in people with T2D, says Dan Azagury, MD, the section chief of minimally invasive and bariatric surgery at Stanford University in Palo Alto, California. Dr. Azagury was not involved in the trial.
“That had led to its FDA approval for use in diabetes. But the weight loss results were game changing in that trial already. This is a study for the FDA; it’s necessary to get the indication for use to treat obesity. But [it’s] nothing very new scientifically — more a confirmation of what we all knew,” says Azagury.
Mounjaro Safety and Side Effects
The overall safety profile of tirzepatide was similar to that reported in earlier trials. “As we would expect, GI issues are going to be the most common side effects. This is common among this category of medicines,” says Stanford.
Nausea, diarrhea, vomiting, and constipation were the most frequently reported side effects, and were generally mild to moderate in severity, usually occurring during the dose-escalation period, according to the findings.
“The discontinuation rates (how many people dropped out before the trial ended) are relatively low, especially in a trial like this in this population,” she says.
The drug carries a warning for a risk of thyroid C-cell tumors, as Mounjaro causes thyroid C-cell tumors in rats. It is unknown whether Mounjaro causes such tumors, including medullary thyroid cancer, in humans.
According to the prescribing information, Mounjaro should not be used in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia syndrome type 2.
Will an FDA Approval Improve Access to Mounjaro?
Azagury says that physicians already knew that the drug could be used off-label to treat obesity. “This new study opens the door to its approval by the FDA. In turn, it will hopefully lead to broader insurance reimbursement. That’s the main barrier we face now: The drugs work; our patients need them. But they can’t get access because the cost is prohibitive, and insurance won’t cover it,” he says.
This reality also impacts patients with lower socioeconomic statuses more than others, increasing health inequities, because they are more often impacted by this disease and are denied access to treatment, says Azagury.
The list price of Mounjaro is $1,023.04 per fill, which contains a four-week supply. Without insurance coverage, the drug costs over $50,000 a year. How much a person actually pays out of pocket depends on insurance coverage.
Stanford agrees that coverage is key. “If you can’t get access to the medicine, it’s like a shiny ornament on a shelf that you can’t reach. That doesn’t help me or my patients. If a lot of people can’t get it — or if they get approved initially and then after three months they’re rejected from approval — imagine how discouraging that is,” she says.
The weight loss that comes with Mounjaro and other drugs in this class can be life-changing, says Stanford. “This isn’t about how someone looks — it’s improving their entire cardiometabolic health,” she says.
As with many other chronic disease treatments, a person needs to stay on Mounjaro throughout their lifetime to treat both diabetes and overweight and obesity, says Stanford.
FDA Approval of Mounjaro to Treat Obesity and Overweight Could Come Before the End of 2023
The company plans to complete its “rolling” submission of the drug for approval in adults with obesity or overweight with weight-related comorbidities in the coming weeks. FDA approval could come as early as late 2023, per the release.
A rolling review is part of the “fast track” approval process, designed to get important new drugs to patients faster, according to the agency. A rolling review means that a drug company can submit completed sections of their new drug application (NDA) for review by the FDA rather than wait until every section of the NDA is completed.
In December 2022, Mounjaro was added to the FDA’s drug shortage list. If the drug gets the nod for the overweight or obesity indication, demand is expected to grow even higher. According to a Reuters report, the company plans to double manufacturing capacity by the end of 2023.