Mounjaro Beats Wegovy in Head-to-Head Weight-Loss Trial as Blockbuster Drug Reshapes Obesity in the US and UK

Eli Lilly's tirzepatide, sold as Mounjaro and Zepbound, produced substantially more weight loss than Novo Nordisk's Wegovy in the first head-to-head trial of the two leading obesity drugs. Those results helped tirzepatide overtake Merck's cancer drug Keytruda as the world's best-selling medicine. At the same time, surveys in the United States and Britain suggest the drugs are changing obesity rates, shopping habits and what the medicines are mainly used for.

Head-to-head results

In the SURMOUNT-5 trial, published in the New England Journal of Medicine, adults with obesity who took tirzepatide lost an average of 20.2% of their body weight over 72 weeks, about 50 pounds. Those on semaglutide, the active ingredient in Wegovy, lost an average of 13.7%, about 33 pounds.

The Lilly-sponsored phase 3b study enrolled 751 adults with obesity but without type 2 diabetes at 32 sites in the United States and Puerto Rico. Participants received the maximum tolerated doses of each drug along with diet and exercise counseling.

About 32% of people on tirzepatide lost at least a quarter of their body weight, compared with 16% on semaglutide. Tirzepatide also produced a greater reduction in waist circumference. Side effects were similar in both groups: about 44% of each reported nausea and about 25% reported abdominal pain.

"Doctors, insurance companies and patients are always asking, 'which drug is more effective?'" said Dr. Louis Aronne of Weill Cornell Medicine and NewYork-Presbyterian, who led the study. "This study allowed us to do a direct comparison."

Researchers believe the difference comes from how the drugs work. Semaglutide mimics a single gut hormone, GLP-1, which regulates appetite and blood sugar. Tirzepatide acts on both the GLP-1 and GIP hormone receptors.

The trial had limitations. It was not blinded, because the drugs come in labeled injection pens, so participants knew which medicine they were taking. Aronne is a paid consultant to Lilly and also serves on an advisory board for Novo Nordisk.

The world's top-selling drug

The results have strengthened tirzepatide's commercial lead. In the first quarter of 2026, Mounjaro generated $8.7 billion in sales, surpassing Keytruda's $7.9 billion. Keytruda had been the world's top-selling drug since early 2023.

Mounjaro and Zepbound share the same active ingredient. Together they brought in $36.5 billion in 2025, compared with $31.6 billion for Keytruda.

"It makes sense that we're shifting from King Keytruda to King Tirzepatide," Evan Seigerman, managing director at BMO Capital Markets, told Bloomberg. "It's not a surprise to me."

US obesity rate falls

The rise of the drugs has coincided with the first sustained decline in U.S. obesity in years.

A Gallup National Health and Well-Being Index report released last year found the adult obesity rate fell to 37% in 2025 from a record 39.9% in 2022. The report described it as "a statistically meaningful decrease representing an estimated 7.6 million fewer obese adults."

Over the same period, the share of U.S. adults who said they were taking a GLP-1 drug for weight loss more than doubled, from 5.8% in February 2024 to 12.4%. The largest declines in obesity were among adults aged 40 to 64, the age groups with the highest use of the drugs.

The survey does not prove the medicines caused the decline. It relied on self-reported height and weight, which can introduce bias. It also found that type 2 diabetes remained at an all-time high, with 13.8% of respondents reporting a diagnosis.

Britain's rapid uptake

Uptake has also surged in Britain, much of it outside the state-run National Health Service.

A University College London study published in January estimated that 4.5% of adults in England, Wales and Scotland, about 1 in 20, had used one of these medications for some reason in the past year. About 1.6 million people used them for weight loss.

"This usage far exceeds NHS England's initial goal of prescribing these drugs to 220,000 people over three years," said lead author Sarah Jackson.

Co-author Clare Llewellyn said, "Our findings suggest many people are accessing these medications outside the NHS."

Sales figures reported by British newspapers last year showed about 2.49 million packs of Mounjaro and Wegovy sold in July 2025, roughly seven times the 493,000 sold a year earlier.

Health experts have warned that the drugs are not a cure. Jo Harby, director of health information at Cancer Research UK, said the medications are "not a silver-bullet, as evidence suggests most people regain weight after treatment."

Changing consumer habits

The effects reach well beyond the doctor's office.

A survey released last week by consulting firm EY-Parthenon found that 54% of U.S. GLP-1 users now take the drugs mainly to manage their weight. It was the first time weight management overtook diabetes and other health conditions as the main reason. The survey covered nearly 15,000 people, including 3,602 current or former users, between March and May. Among users:

• 72% had changed clothing sizes.
• 63% were eating fewer sweets, and 57% had cut back on salty snacks.
• 45% had reduced alcohol consumption.
• 46% had fully or partly switched clothing brands, mostly because of fit.

"Everyone accepts that this is a structural change that's not going away," Don Johnson, a principal at EY-Parthenon, told CBS News. Referring to clothing purchases, he said, "You're losing a lot of weight on the drugs, so you're needing to buy differently."

EY-Parthenon projects that 35% to 40% of U.S. adults will have used a GLP-1 drug by 2033.

From diabetes to weight loss

Both drug classes were first developed to treat type 2 diabetes. Mounjaro was approved in the United States for diabetes in 2022. Lilly later won approval for the same compound for chronic weight management under the brand name Zepbound. Novo Nordisk sells semaglutide as Ozempic for diabetes and Wegovy for weight loss.

Prices remain a major barrier, but they have fallen. Under an agreement between the Trump administration and the two manufacturers, the cost of some of the drugs dropped to between $150 and $350 a month, from about $1,000. Eligible Medicare beneficiaries can get the drugs for $50 a month through a federal program.

Even so, researchers caution that much remains unknown, including how long patients need to stay on the drugs, the long-term effects of sustained use, and why some patients respond poorly.

"The pathways that regulate weight are incredibly complicated," Aronne said. "We still have people who don't respond to them."