In the first head-to-head comparison of two blockbuster drugs used in real-world conditions, people who took Mounjaro lost significantly more weight than their counterparts who took Ozempic — and the longer patients continued to take the drugs, the wider the gap grew.
After three months of weekly injections, patients taking Ozempic lost an average of 3.6 percent of their body weight, while those taking Mounjaro lost an average of 5.9 percent.
After six months, Ozempic patients had lost an average of 5.8 percent of their weight, while Mounjaro patients’ average weight loss was 10.1 percent.
And after a full year, those taking Ozempic had lost an average of 8.3 percent of their weight, while those taking Mounjaro had lost an average of 15.3 percent.
The researchers who conducted the analysis also found that, compared with people taking Ozempic, those taking Mounjaro were 2.5 times more likely to lose at least 10% of their initial weight and more than three times more likely to lose at least 15% of their weight during their first year of treatment.
The results were published Monday in JAMA Internal Medicine.
Dr Matthew Freebyendocrinologist and director of the Gonda Diabetes Center at UCLA’s Geffen School of Medicine, said the study’s results are consistent with what he has observed in his own patients.
“From a weight loss and blood sugar reduction perspective in people with type 2 diabetes, we see stronger effects with Mounjaro than with Ozempic,” said Freeby, who was not involved in the research.
Both drugs have been approved by the U.S. Food and Drug Administration to help people with diabetes control their blood sugar. By mimicking a hormone called glucagon-like peptide 1, or GLP-1, they stimulate the body’s production of insulin, slow digestion, increase feelings of fullness and reduce appetite.
Mounjaro also mimics a related hormone called glucose-dependent insulinotropic peptide, or GIP.
Clinical trials showed that both drugs helped patients lose significant weight. Tirzepatide, the active ingredient in Mounjaro, was more effective than semaglutide, the active ingredient in Ozempic. But the trials were not conducted under the same conditions, so the results are not directly comparable.
Researchers at Truveta, a medical data and analytics company owned by 30 health systems, sought to address this problem by examining their store of electronic medical records. The work also gave them a chance to see how patients fared outside the ideal setting of a clinical trial, which typically offers free medications, regular checkups and other support.
Using their database, the researchers were able to track people who filled their first prescription for either drug between May 2022 — the month Mounjaro joined Ozempic in receiving FDA approval — and September 2023. Patients did not need to have type 2 diabetes to be included in the study, but they did have to be overweight (with a body mass index of at least 27) or obese (with a BMI of at least 30).
The Truveta team identified about 41,000 people in more than 30 states who met all of the study’s inclusion criteria. Because patients treated with Ozempic outnumbered those treated with Mounjaro by three to one, the researchers used information about age, race, income, medical history and other factors to create a group of Ozempic patients that best matched the Mounjaro patients. The result was a population of nearly 18,400 people split evenly between the two drugs.
Before the first dose of the drug, the average weight of people in both groups was 110 kg. But it didn’t take long for the two groups to diverge.
After accounting for unmeasured influences that could have skewed the results, the Truveta team found that the amount of weight lost was 2.4 percentage points higher for Mounjaro patients than for Ozempic patients after three months, 4.3 percentage points higher after six months, and 6.9 percentage points higher after one year.
Mounjaro also outperformed Ozempic in terms of how well people achieved various milestones within a year of starting treatment with either drug.
Nearly 82% of Mounjaro patients lost at least 5% of their body weight, compared to 67% of patients taking Ozempic. Similarly, 62% of Mounjaro patients and 37% of Ozempic patients lost at least 10% of their initial weight, while 42% of Mounjaro patients and 18% of Ozempic patients lost at least 15% of their initial weight.
The researchers did not examine the biological mechanisms of the two drugs, but study leader Tricia Rodriguez, a senior applied scientist at Truveta Research, said Mounjaro may have been more effective because it works in two ways instead of just one.
Dr. Ken Fujioka, an endocrinologist who heads the Nutrition and Metabolism Research Center at Scripps Clinic in San Diego and was not involved in the study, noted that the FDA approved a higher dose of Ozempic in March 2022, but many doctors were unaware of it during the study period. With proper dosing, he said, patients taking Ozempic would have had better results.
“I think Mounjaro is more effective at losing weight than Ozempic,” said Fujioka, who has received consulting and speaking fees from the makers of both drugs. “I just don’t know by how much.”
The big difference in effectiveness was not accompanied by a measurable difference in the rate of moderate or serious side effects like bowel obstruction and pancreatitis, which were rare for patients in both groups. The researchers didn’t compare the risk of milder problems like nausea and vomiting because people didn’t necessarily report them to their doctors, Rodriguez said.
Regardless of the drug taken, patients with type 2 diabetes lost less weight than patients without the disease, the researchers found.
This could be because some diabetes treatments can cause weight gain and some patients eat more throughout the day to keep their blood sugar levels from dropping too low, Freeby said.
DNA is likely a factor, Fujioka added. “Individuals who have the genes to become diabetic probably have the genes to gain weight and keep it off better,” he said.
It’s also possible that people who sought prescriptions for Ozempic or Mounjaro to lose weight were more motivated to keep taking the drug even though it was expensive or caused unpleasant side effects, or that they were more likely to engage in other weight-loss behaviors, Rodriguez said.
“Determining this point is a crucial topic for future research,” she said.
People currently taking Ozempic probably have a more pressing question on their minds: Should I switch to Mounjaro?
Dr. Nick StuckyAn infectious disease physician at Providence Portland Medical Center and lead author of the study, said the findings alone should not prompt patients to stop taking a medication that works for them. The risk of side effects, insurance coverage and availability of the medications are also factors to consider.
“Although tirzepatide was significantly more effective than semaglutide, patients on both drugs experienced substantial weight loss,” said Stucky, who is also vice president of research at Truveta.
Freeby supported this view.
“If someone is doing well on a drug, why wreak havoc?” he said.
Freeby added that Ozempic (and its sister drug Wegovy, which is FDA-approved specifically for weight loss) has at least one advantage over Mounjaro (and Zepbound, its weight-loss counterpart): In clinical trials, Ozempic has been shown to reduce the risk of heart attacks, strokes and other cardiovascular problems as well as kidney failure.
“At this point, we don’t have a lot of data on Mounjaro in terms of secondary outcomes,” he said.