Zepbound Challenges Ozempic with FDA-Approved Weight Management Breakthrough

The FDA recently approved Zepbound, a new injectable medication for weight loss management, but how does it stack up to the ultra-popular diabetes/weight loss drug Ozempic?

Over the past year, drugs like Ozempic, Wegovy, and Mounjaro have proven to be highly effective for weight loss and diabetes management. Their ongoing popularity among people who want to lose weight or manage diabetes has fueled heated competition between pharmaceutical companies to develop the next big weight loss contender.

On November 8, another new weight-loss medication — AKA Zepbound (tirzepatide) — gained FDA approval. This new drug, made by Eli Lilly, is approved for chronic weight management in adults with obesity or who are overweight and who also have at least one weight-related health condition such as high cholesterol, type 2 diabetes, or high blood pressure. Although the drug's name differs, its active ingredient is the same compound found in Mounjaro.

But how does Zepbound compare to Ozempic and other medications currently dominating the weight-loss drug market?

What is Zepbound?

Zepbound activates GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors. It's administered by injection once a week and comes in six different doses, from 2.5 to 15 mg.

People without diabetes taking the highest dose of Zepbound while also engaging in a diet and exercise plan lost 48 pounds on average during a 72-week trial, and those taking the lowest dose lost around 34 pounds.

Moreover, Zepbound's active ingredient differs from semaglutide-based weight loss/diabetes drugs like Ozempic and Wegovy. Semaglutide is a GLP-1 agonist, while tirzepatide is a GLP-1 agonist and acts on GIP receptors in the intestines.

How is Zepbound different from Mounjaro?

While both medications have the same active ingredient, Mounjaro is approved for diabetes management, and Zepbound is approved for weight loss.

"[Zepbound] is exactly the same as Mounjaro," Mitchell Roslin, M.D., FACS, FASMBS, told Healthnews. Roslin is a board-certified bariatric surgeon and Chief of Bariatric Surgery at Northwell Lenox Hill Hospital in New York City.

Roslin says because of FDA labeling, Zepbound is marketed for a different indication, and the drug manufacturer does this for monetary reasons.

"It really starts the patent over again, [at least parts of it]," Roslin explained. "In other words, they've added to their patent, so it gives them more protection in the future. And then, they do a separate trial so that they can market it for that indication. Now, it could be given in different doses, but it's the same exact drug."

Is Zepbound more effective than Ozempic or Wegovy?

Roslin says medications such as Ozempic, Wegovy, Mounjaro, and Zepbound are all highly effective. However, in clinical trials, Mounjaro, which has the same active ingredient as Zepbound, appeared to be slightly superior for weight loss.

Still, Roslin notes that these medications might not be the best option for some people.

"Compared to bariatric surgery, the majority of people in these [weight loss drug] trials had class one and class two obesity, not high class three obesity," Roslin explained.

So, Roslin says that for some people, these medications are not going to be the answer for severe obesity.

"The other thing is, whatever you do for obesity, you have to do forever. So, this means that people are going to need to be maintained on these drugs or what comes after them for a lifetime," Roslin said. "And if you withdraw the drug, people are [going to experience] what's called metabolic compensation, and they'll regain their weight."

Roslin explained that when a person has a high BMI, it impacts the sympathetic and parasympathetic nervous systems, which are competing systems. In people with obesity, the sympathetic nervous system is in overdrive, resulting in a higher heart rate and blood pressure. In contrast, a person experiences excessive parasympathetic nervous system activity when they lose weight.

"As a result, [a person experiences] weight gain," Roslin said. "Now, the difference between bariatric surgery is you're left with the operation which still limits [food] intake to some extent, but [with] these medications when you stop, you're going to really regain weight."

Zepbound's potential side effects

According to the FDA, Zepbound can cause nausea, diarrhea, vomiting, constipation, stomach discomfort, injection site reactions, fatigue, allergic reactions, burping, hair loss, and gastroesophageal reflux disease.

Zepbound has also caused thyroid C-cell tumors in rats, but it's unclear if the drug could lead to thyroid cancer in humans. Prescribing information also includes warnings about the potential for pancreatitis, low blood sugar, acute kidney injury, specific types of retinal damage, and suicidal thoughts or behaviors.

However, Roslin says that Mounjaro, which contains the same active ingredient as Zepbound, may have slightly fewer gastrointestinal side effects than semaglutide.

Still, the adverse health effects of obesity may outweigh any potential side effects of these medications.

Roslin asserts that obesity is a systemic disease, and people with obesity are physiologically 12 years older than their chronological age.

"People who have an elevated BMI, they stop existing, there are no heavy people in nursing homes," Roslin said. "Yes, [these medications] have risks, but these risks are less than the risks of having severe obesity and metabolic dysfunction."

How much does Zepbound cost?

Eli Lilly says that Zepbound will hit the United States market by the end of 2023 for a list price of $1,059.87 before insurance, which is 20% lower than 2.4 mg semaglutide injections. However, if an individual's insurance covers the drug, they may be eligible for a Zepbound one- or three-month prescription for as low as $25.

Those with insurance policies that do not cover the medication might be eligible to pay as low as $550 for a one-month prescription, which Eli Lilly says is 50% lower than the list price.

What does the future look like for people taking Zepbound, Ozempic, and similar drugs?

Individuals who are interested in taking weight loss medications may have more to choose from in the near future. For example, Novo Nordisk plans to test its newest weight-loss medication CagriSema in a phase 3 trial. CagriSema is a combination of an investigational medication called cagrilintide and a fixed dose of Wegovy.

In addition, mazdutide, a GLP-1 and GCGR receptor dual agonist developed by a Chinese pharmaceutical firm, has shown promise in phase 2 clinical trials.

Still, because these medications are relatively new, the long-term effects are not fully understood. Roslin says much of this remains to be seen.

Nonetheless, weight loss drugs may be more expensive in the U.S., and many people may choose to stop taking them, which will likely result in weight regain.

"And that's why even though bariatric surgery is 5-12% down now because of these medications, it will all increase again," Roslin said.

Roslin suggests this increase will occur because more people will want aggressive weight management solutions after successfully losing weight while taking Zepbound, Ozempic, and other weight-loss medications.