In the first head-to-head comparison of two blockbuster drugs used in real-world conditions, people taking Mounjaro lost significantly more weight than their counterparts taking Ozempic — and the longer patients continued taking the drugs, the bigger the difference became.
After three months of weekly injections, patients taking Ozempic lost 3.6% of their body weight, on average, while those taking Mounjaro lost an average of 5.9%.
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 when a full year had passed, those taking Ozempic had lost an average of 8.3% of their weight, while those taking Mounjaro had lost an average of 15.3%.
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 percent of their initial weight and more than three times more likely to lose at least 15 percent of their weight during the first year of taking the drugs.
The findings were published Monday in JAMA Internal Medicine.
Dr. Matthew Freebyendocrinologist and director of the Gonda Diabetes Center at the UCLA Geffen School of Medicine, said the study results are in line with what he has seen in his own patients.
“From a weight loss and sugar reduction perspective for those with type 2 diabetes, we see stronger effects with Mounjaro compared to 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 keep their blood sugar under control. By mimicking a hormone called glucagon-like peptide 1, or GLP-1, they increase 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.
When the drugs were tested against placebos in clinical trials, both helped patients lose a significant amount of weight. Tirzepatide, the active ingredient in Mounjaro, appeared to be 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 health data and analytics company owned by 30 health systems, sought to remedy that by examining their trove of electronic health records. The work also gave them a chance to see how patients fared outside the idealized setting of a clinical trial, which typically provides free medications, regular checkups and other support.
Using their database, the researchers were able to identify people who filled their first prescription for either drug between May 2022 — the month Mounjaro teamed up with Ozempic to receive FDA approval — and September 2023. Patients did not need to have type 2 diabetes to be included in the study, but they did need to be overweight (with a body mass index of at least 27) or obese (with a BMI of at least 30).
The Truveta team found about 41,000 people in more than 30 states who met all the criteria to be included in the study. Because Ozempic patients outnumbered Mounjaro patients by 3 to 1, the researchers used information on age, race, income, health history and other factors to arrive at a group of Ozempic patients that most closely matched Mounjaro patients. The result was a population of nearly 18,400 who were evenly split between the two drugs.
Before the first dose of the medication, the average weight of people in both groups was 243 pounds. But it wasn’t long before the two groups diverged.
After accounting for unmeasured influences that could have skewed the results, Truveta’s team found that the amount of weight lost was 2.4 percentage points greater for Mounjaro patients than for Ozempic patients after three months, 4.3 percentage points greater after six months, and 6.9 percentage points greater after one year.
Mounjaro also surpassed Ozempic in terms of people’s success in reaching various milestones within a year of starting to take either drug.
Nearly 82% of Mounjaro patients lost at least 5% of their body weight, compared with 67% of patients taking Ozempic. Similarly, 62% of Mounjaro patients and 37% of Ozempic patients lost at least 10% of their starting weight, while 42% of Mounjaro patients and 18% of Ozempic patients lost at least 15% of their starting weight.
The researchers did not examine the biological mechanisms of the two drugs, but study leader Tricia Rodriguez, a principal 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 leads the Scripps Clinic Nutrition and Metabolic Research Center in San Diego and who was not involved in the study, noted that the FDA approved a higher dose of Ozempic in March 2022, but that many doctors were unaware of it during the study period. With the proper dosage, he said, patients on Ozempic would have seen better results.
“I believe Mounjaro actually gives more weight loss than Ozempic,” said Fujioka, who has received consulting and speaking fees from the makers of both drugs. “I’m just not sure how much.”
The large gap in effectiveness was not accompanied by a measurable difference in the rate of moderate or severe side effects, such as bowel obstructions and pancreatitis, which were rare for patients in both groups. The researchers did not compare the risk of milder problems, such as nausea and vomiting, because people would not necessarily report them to their doctors, Rodriguez said.
Regardless of the medication they took, patients with type 2 diabetes lost less weight than patients without the disease, the researchers found.
This may be explained by the fact that certain diabetes treatments can cause weight gain, and that some patients eat more throughout the day to keep their blood sugar levels from getting too low, Freeby said.
DNA is likely a factor, Fujioka added. “Individuals who have the genetics to become diabetic probably have the genetics to gain weight and keep it off better,” he said.
It’s also possible that people who sought prescriptions for Ozempic or Mounjaro with the goal of losing weight were more motivated to continue taking the drug, even if it was expensive or caused uncomfortable side effects, or that they were more likely to engage in other behaviors that promoted weight loss, Rodriguez said.
Figuring this out is “a crucial topic for future research,” she said.
People currently taking Ozempic probably have a more pressing question on their mind: should I switch to Mounjaro?
Dr. Nick StuckyAn infectious disease physician at Providence Portland Medical Center and senior author of the study, said the results alone shouldn’t cause patients to stop taking a drug that’s working for them. The risk of side effects, insurance coverage and drug availability are also things to consider.
“Although tirzepatide was significantly more effective than semaglutide, patients taking both drugs experienced substantial weight loss,” said Stucky, who is also Truveta’s vice president of research.
Freeby supported this view.
“If someone is doing well on a drug, why do it?” 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.
“Right now, we don’t have a lot of data on Mounjaro as far as secondary outcomes,” he said.
