In the first direct 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 took the drugs, the wider the gap became.
After three months of weekly injections, patients taking Ozempic lost an average of 3.6% of their body weight, while those taking Mounjaro lost an average of 5.9%.
At six months, Ozempic patients had lost an average of 5.8% of their weight, while Mounjaro patients' average weight loss was 10.1%.
And after a full year, 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% of their starting weight and more than three times more likely to lose at least 15% of their weight during their first year taking the drugs.
The findings were published Monday in JAMA Internal Medicine.
Dr. Matthew Freebyendocrinologist and director of the Gonda Diabetes Center at the Geffen School of Medicine at UCLA, said the study's results are consistent with what he has seen in his own patients.
“From a weight loss perspective and from a 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 were 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 healthcare data and analytics company owned by 30 health systems, tried to address this problem by examining their collection of electronic medical records. The work also gave them a chance to see how patients were faring outside the idealized context of a clinical trial, which typically offers free medication, regular check-ups 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 joined Ozempic in seeking 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 a 3-to-1 margin, the researchers used information about age, race, income, medical history and other factors to create a group of Ozempic patients that more closely matched the Mounjaro patients. The result was a population of nearly 18,400 people who were evenly split between the two drugs.
Before the first dose of the drug, 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, the Truveta 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 outperformed Ozempic in terms of people's success in reaching several milestones within a year of starting one of the drugs.
Nearly 82% of Mounjaro patients lost at least 5% of their body weight, compared with 67% of patients taking Ozempic. Also, 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.
The big difference in efficacy 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 in patients in both groups. Researchers did not compare the risk of milder problems, such as nausea and vomiting, because people did not necessarily report them to their doctors, Rodriguez said.
The researchers found that regardless of which drug they took, patients with type 2 diabetes lost less weight than patients without the disease. This could 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 from getting too low, Freeby 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 promote weight loss, Rodriguez said.
Finding this out is “a crucial topic for future research,” he 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 on the study, the results alone shouldn't cause patients to stop taking a drug that's working for them. Risk of side effects, insurance coverage and drug availability are also factors to consider.
“While 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 that view.
“If someone is doing well on a medication, why upset the established order?” he asked.
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.
