Zepbound: FDA-Approved Medicine for Weight Loss. Does It Work?

For years, conventional wisdom has been that weight loss is a matter of willpower. Those who are overweight or obese just need to try harder to eat less and exercise more. But while diet and exercise will always play an outsized role in weight management, millions of Americans struggle to control their weight despite eating healthy and being physically active.

New medications are proving that the challenge faced by 70% of Americans in managing their weight extends beyond willpower, but involves many other metabolic and genetic factors.

In fact, the prevalence of obesity has gradually risen over the past decade to around 33% of the U.S. population, according to a recent HealthCanal report. Severe obesity, defined as a body mass index of 40 or higher, is found in 9.2% of adults.

“Obesity is an epidemic in our country and associated with several chronic health conditions, such as Type 2 diabetes and heart disease,” says Dr. Lydia Alexander, chief medical officer for Enara Health in San Mateo, California and president-elect of the Obesity Medicine Association. “There is increased understanding that obesity is a neuroendocrine disorder rather than a failure of willpower as more effective anti-obesity medications are approved (by the Food and Drug Administration).”

Zepbound, chemically known as tirzepatide, is the newest weight loss medication approved by the FDA. Originally approved for Type 2 diabetes under the brand name Mounjaro, Zepbound has generated a lot of excitement for those looking to lose weight.

A dual-targeted or dual-agonist medicine, Zepbound uniquely activates two hormone receptors simultaneously: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. While its exact mechanism is unclear, tirzepatide both helps improve glucose control and targets the appetite centers of the brain that initiate a feeling of fullness. 

“This agent is part of a completely new class of drugs,” says Dr. Cecilia Low Wang, an endocrinologist with UCHealth and professor of medicine at the University of Colorado School of Medicine in Aurora, Colorado. “Its dual action not only promotes the release of insulin, but leads people to eat less, feel fuller and, therefore, lose weight.”

Zepbound has been clinically shown to help people lose 15% to over 26% of their body weight, depending on the dosage.

The SURMOUNT-3 and SURMOUNT-4 trials conducted by Eli Lilly and Company, the manufacturer of Zepbound, found that patients with obesity taking the medicine experienced up to a 26.6% weight loss over the course of 84 weeks.

In another major study, published in the New England Journal of Medicine, Zepbound was evaluated in adults with obesity and at least one weight-related comorbidity, excluding diabetes. The trial included more than 2,500 adults with a mean body weight of 230 pounds who were randomly assigned to receive either a weekly subcutaneous injection of 5, 10 or 15 milligrams of Zepbound or placebo for 72 weeks. Participants were provided counseling to reduce caloric intake by 500 calories a day and were directed to exercise 150 minutes per week.

At the end of the study, the average decrease in weight was 15% for those taking a 5 milligram dose, 19.5% for those taking a 10 milligram dose and 20.9% for those taking a 15 milligram dose. Comparatively, the average decrease in weight in the placebo group was 3.1%. There were also improved cardiovascular and metabolic measures found in those taking Zepbound.

“What this means is that for someone who weighs about 200 pounds, they will lose on average about 28 pounds on tirzepatide,” says Dr. Reshmi Srinath, associate professor and director of weight and metabolism management program at the Icahn School of Medicine at Mount Sinai in New York City. “These findings open up promising new options not only for Type 2 diabetes management, but also offering the potential dual benefit of blood sugar control and weight management.”

Zepbound – or any weight loss medicine – is not a golden ticket to a healthier weight without adopting healthier habits. These medications are most successful when combined with healthy lifestyle changes and are not meant as a replacement for them. Also, if a patient has to stop taking it without adopting healthier lifestyle habits, some – if not all – weight can be regained.

“Similar to discontinuing blood pressure or thyroid medication, we would expect suddenly stopping weight managing medications without addressing underlying causes to result in weight gain back to previous levels,” Alexander says.

Zepbound is available in six dosage forms, including 2.5 milligrams, 5 milligrams, 7.5 milligrams, 10 milligrams, 12.5 milligrams or 15 milligrams. The starting dose is 2.5 milligrams taken weekly as a self-injectable. After four weeks, the dose is increased in increments of 2.5 milligrams until an effective dose is reached or to the maximum level of 15 milligrams.

“By starting off with a low dose and then increasing the dose helps improve the medicine’s tolerability,” explains Low Wang, who also serves as the chair of the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee.

In clinical studies, the most common side effects of Zepbound that were reported include:

Other more serious side effects may include:

Doctors advise against prescribing the drug for people with severe stomach problems. In rare cases, severe gastrointestinal issues – such as stomach paralysis, pancreatitis and intestinal obstructions – may occur. Common symptoms include bloating, nausea, vomiting, abdominal pain, constipation and breath odor. If you experience any of these signs, talk with your health care provider immediately.

In clinical studies, adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2% and 2.6% of participants receiving 5, 10 and 15 milligrams of Zepbound and placebo, respectively. 

“It’s a low percentage of people who have side effects. The majority of people tolerate this medication very well,” Low Wang says. 

While studies show that tirzepatide is safe overall, the long-term effects are still unknown and need to be further evaluated. 

Zepbound and Mounjaro are the brand names for the same drug tirzepatide. However, there are similarities and differences.

Another GLP-1 receptor agonist that has gotten a lot of attention is semaglutide, the active ingredient in Ozempic and Wegovy. Semaglutide, like tirzepatide, was also initially developed for diabetes under the brand name Ozempic and has since been approved to treat obesity under the brand name Wegovy.

Traditional beliefs about weight loss have focused mainly on willpower, but new medications like Zepbound are changing misperceptions around weight loss treatment.

It’s important to note that the drug is not a substitute for a healthy lifestyle, and long-term success is maximized when combined with a well-balanced diet and exercise regimen.

Check with your insurance company to see what coverage is available. There are ways to save through manufacturer’s coupons and patient assistance programs.