With so many weight loss medications on the market, it’s easy to feel overwhelmed by the options. From brand-name heavy hitters to compounded varieties, each promises to help shed pounds. But a recent head-to-head trial comparing Zepbound vs. Wegovy provided new insights into their effectiveness, making the choice slightly clearer. The findings? Zepbound led to an average weight loss of 20.2 percent compared to Wegovy’s 13.7 percent. We talked with healthcare experts to understand the study’s findings, what sets these drugs apart and how to choose the best option.
How Zepbound and Wegovy work
Zepbound (tirzepatide) and Wegovy (semaglutide) both support weight loss by targeting hormones that influence appetite and metabolism. However, their mechanisms differ significantly.
Which weight loss drug would you be most interested in trying?
“[Zepbound] is a dual agonist targeting GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) receptors,” explains Rebecca Emch, PharmD, Vice President of Pharmacy and Medical Operations at Eden. Put simply, it activates two pathways, also known as a dual-action approach. “By engaging both pathways, [Zepbound] amplifies insulin secretion, slows gastric emptying and reduces appetite,” says Dr. Emch, which helps regulate blood sugar levels. She adds that tirzepatide may also improve other health conditions, including obstructive sleep apnea and cardiovascular health.
Wegovy, on the other hand, focuses on just one pathway as a mono GLP-1 receptor agonist, mimicking the natural GLP-1 hormone which regulates appetite and slows digestion. “Beyond weight loss, Wegovy has shown cardiovascular benefits such as reducing the risk of major adverse cardiovascular events in obese or overweight patients with heart disease,” says Dr. Emch.
The key differences? “Zepbound’s dual mechanism may offer broader metabolic benefits, while Wegovy’s established cardiovascular data makes it a strong choice for heart health considerations,” notes Dr. Emch.
The effectiveness of Zepbound vs. Wegovy
On December 4, 2024, pharmaceutical company Eli Lilly announced results from its SURMOUNT-5 clinical trial comparing its dual-acting drug Zepbound to its competitor Novo Nordisk’s Wegovy. According to the press release, Zepbound is the only FDA-approved dual GIP and GLP-1 receptor agonist weight loss medication.
The findings showcased Zepbound’s standout efficacy, with participants losing 50.3 lbs on average compared to 33.1 lbs with Wegovy. Additionally, nearly 32 percent of those taking Zepbound achieved at least 25 percent body weight loss, a significant milestone compared to 16.1 percent on Wegovy.
However, it’s important to remember that effectiveness largely depends on individual experience. “While [these results] may make it sound like Zepbound is always better, that is not necessarily true,” explains Javad Sajan, MD, Cosmetic Plastic Surgeon at Allure Esthetic Plastic Surgery. “People respond differently to each medication and based on their medical history and body composition, they may do better on one versus the other.”
Side effects: What to expect from Zepbound vs. Wegovy
Like many medications, both Zepbound and Wegovy come with potential side effects, primarily gastrointestinal issues. “[Both] can both cause nausea, upset stomach, vomiting and bowel issues,” says Dr. Sajan. “Typically, side effects improve with continued use of medication. If a patient experiences severe side effects on one medication, they may do better on the other.” However, he emphasizes that tolerability varies widely from person to person for either medication.
“Anecdotal evidence suggests that [Zepbound] may cause slightly higher rates of gastrointestinal discomfort, likely due to its dual receptor action, but this varies by individual,” adds Dr. Emch. Activating two pathways can intensify hormonal changes in the body. It’s worth restating the importance of starting with lower doses and gradually increasing them, a standard practice with both medications, to minimize commonly reported side effects.
Zepbound vs. Wegovy: accessibility and cost
Access to these medications can depend heavily on insurance coverage and affordability. “Wegovy costs approximately $1,349 per month,” says Dr. Emch. According to Eli Lilly, Zepbound costs $1,060 per month without insurance. “Affordability for both drugs remains a challenge, with out-of-pocket costs potentially high for those without insurance,” adds Dr. Emch.
However, Dr. Sajan notes that “there are options and for people with certain medical conditions, insurance may cover their medications when prescribed by their normal doctor.” Coverage also depends on the specific policy and the patient’s health conditions, adds Dr. Emch.
Eli Lilly’s Zepbound is relatively new to the market, so its availability may be more limited compared to Wegovy, which has been on the market longer. It’s best to check in with your insurance provider to understand your coverage and explore patient assistance programs from the manufacturer to reduce out-of-pocket costs.
Which weight loss medication is right for you?
So, is Zepbound or Wegovy better when it comes to long-term weight loss? “One is not overall better than the other. They are very similar medications and they each have areas where they excel,” says Dr. Sajan. And of course, pairing the medication with a healthy diet and exercise will help deliver the best results.
Moreover, choosing between Zepbound and Wegovy depends on your unique circumstances. “[Patients] should consult their healthcare provider to evaluate the best option based on their health profile and treatment goals,” advises Dr. Emch. “Both drugs are highly effective, but the choice will depend on individual factors like comorbidities, cost and treatment preferences.”
This content is not a substitute for professional medical advice or diagnosis. Always consult your physician before pursuing any treatment plan.
