Zepbound leads to more weight loss than Wegovy, Eli Lilly says

A new study is shedding light on which of two drugs currently approved by the U.S. Food and Drug Administration for weight loss is most effective at helping people lose more weight in less time.

Zepbound, a drug with the main active ingredient tirzepatide, was found to be more helpful in helping people lose weight than Wegovy, a drug with the main active ingredient semaglutide, according to new data released Wednesday by Eli Lilly, the maker of Zepbound.

The study, which has not yet undergone peer review, included 751 people with obesity, or those who were overweight with a related medical condition.

While both medications showed a significant weight loss benefit, after 72 weeks on treatment, people treated with Zepbound lost 20% of their body weight, compared to people on Wegovy who lost just under 14%.

This translates to people on Zepbound losing roughly 50 pounds compared to 33 pounds on Wegovy during the 72-week trial.

The newly released clinical trial data comes on the heels of another study published in July that found Mounjaro, which also has tirzepatide as its main active ingredient, was more effective for weight loss than Ozempic, whose main active ingredient is semaglutide.

Both Ozempic, made by Novo Nordisk, and Mounjaro, made by Eli Lilly, are FDA-approved to treat Type 2 diabetes, but some doctors prescribe the medication "off-label" for weight loss, as is permissible by the FDA.

Wegovy, also made by Novo Nordisk and with the same active ingredient as Ozempic, and Eli Lilly's Zepbound, with the same active ingredient as Mounjaro, are FDA-approved for weight loss.

The drugs, typically taken once weekly as injections, work by helping the pancreas increase the production of insulin to move sugar from the blood into body tissues.

They also slow down the movement of food through the stomach and curb appetite, thereby causing weight loss.

Dr. Louis Aronne, a principal investigator on the clinical trial involving Zepbound and Wegovy, told ABC News that the success of drugs using tirzepatide is likely because the ingredient targets two hormones instead of one.

Tirzepatide, used in Zepbound and Mounjaro, targets both the GLP-1 and the GIP receptor agonist, while semaglutide, found in Wegovy and Ozempic, mimics only the GLP-1 receptor agonist, a type of hormone in the body that impacts everything from the brain to muscle to the pancreas, stomach and liver.

"It supports the idea that dual mechanisms of action will producer greater weight loss," Aronne, also the Sanford I. Weill Professor of Metabolic Research and director of the Comprehensive Weight Control Center at Weill Cornell Medicine, said of the study's findings, which he described as "not a surprise."

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Aronne noted that the body naturally releases seven to eight hormones when food is consumed in order to provide a sense of fullness. The fact that tirzepatide mimics the effects of two hormones produces a "greater effect" when it comes to weight loss, he explained.

"The weight regulating system is very complicated. There are multiple overlapping systems that try to prevent you from losing weight so you don't starve to death," Aronne said. "And so what we've learned over the years is that hitting the system in more than one place can often bring additive weight loss."

While losing a large amount of weight may be the goal for some people, for others, it is not, which is why it's important that multiple drugs are available, according to Aronne.

"We now have more than two years of experience using these medicines for weight loss, and what we're seeing is that, in some cases, one drug is better, it has fewer side effects, and perhaps greater efficacy than the other," Aronne said. "And so like many areas of medicine, it depends on the patient."

He continued, "One thing you have to remember is everybody doesn't need the most weight loss. There are people who will benefit from greater weight loss, but not everyone needs the most weight loss."

Novo Nordisk, the maker of Wegovy and Ozempic, said in a statement Wednesday that it "strongly believes" in semaglutide, the main active ingredient in both its medications.

"In combination with diet and exercise, Wegovy is the only obesity medicine proven to reduce the risk of major cardiovascular events such as death, heart attack, or stroke in adults with known heart disease and with either obesity or overweight. These significant CV events were assessed regardless of change in weight in the landmark SELECT trial," the company said in a statement. "People living with obesity deserve solutions and support, including access to FDA-approved options - never shame or blame. As a pioneer and leader in obesity care, we know that treating this misunderstood disease is more than just a number on a scale, and we strongly believe in the semaglutide molecule and the robust data supporting its benefits. Semaglutide has a cumulative exposure of over 22 million patient-years."

"We will continue to invest in a variety of disease states including diabetes, chronic kidney disease, obesity, CV disease, liver disease, and Alzheimer’s disease, as seen in our robust clinical development programs and outcome studies," the statement continued. "Our goal is to provide innovative and person-centric options to support patients living with chronic disease as part of their journey towards better health."

Aronne and other medical specialists also point out that using medication to lose weight also requires cardio and strength training and changing your diet to one that includes proteins and less processed foods with added sugars.

The most commonly reported side effects of medications used for weight loss are nausea and constipation, but gallbladder and pancreatic disease are also reported. Makers of these drugs recommend having a conversation about the side effect profile and personalized risks with a health care professional before starting.