In 2021, the FDA approved Wegovy (semaglutide) as the first new weight-loss medication since 2014, marking it as the pioneering once-weekly medication in its category. Today, a newer medication called Zepbound (tirzepatide) has also entered the market, offering another option for those seeking medical aid for weight loss.
While Zepbound and Wegovy share some similarities, such as being injected once a week and having similar side effects, key differences between them might make one more suitable than the other depending on individual circumstances.
Mechanisms of Action: Similar but Distinct
Both Zepbound and Wegovy are effective in weight management by targeting appetite, hunger, and food cravings to reduce calorie intake. However, they achieve these effects in slightly different ways.
Wegovy belongs to the class of medications known as glucagon-like peptide-1 (GLP-1) agonists. It mimics the action of the natural gut hormone GLP-1, influencing the gut and brain to decrease appetite, increase feelings of fullness, and reduce cravings. Study results indicate that people on Wegovy lose an average of 15% of their body weight from one year of treatment.
Zepbound, on the other hand, acts similarly to GLP-1 but also mimics another gut hormone called glucose-dependent insulinotropic polypeptide (GIP), making it a dual GIP/GLP-1 agonist. The combined effects of GIP and GLP-1 are believed to provide an additive benefit in weight management. Study results indicate an average weight reduction of 21% with Zepbound after 72 weeks of treatment and when titrated up to the highest dose.
Dosage Schedules: Different Paths to the Same Goal
When starting either Zepbound or Wegovy, the dosage is gradually increased over time to manage side effects and determine the optimal dose. However, their dosage schedules differ.
- Wegovy: Begins with a weekly dose of 0.25 mg for four weeks, increasing to 0.5 mg, 1 mg, and 1.7 mg at four-week intervals. The maintenance dose, if tolerated, is 2.4 mg weekly.
- Zepbound: Starts with a weekly dose of 2.5 mg for four weeks, then increases to 5 mg weekly. This dose may be maintained long-term, or, if needed, further increased to 10 mg or 15 mg at four-week intervals.
Weight Loss Outcomes: Zepbound Shows Promise
While ongoing head-to-head clinical trials will provide more definitive comparisons, existing studies suggest Zepbound may result in greater weight loss compared to Wegovy.
- Zepbound: In a 72-week trial, participants on the highest dose (15 mg) lost nearly 21% of their starting body weight on average, with almost 60% achieving a 20% or greater weight reduction.
- Wegovy: In a 68-week trial, participants on the maintenance dose (2.4 mg) lost nearly 15% of their starting body weight on average, with about half achieving a 15% or greater reduction.
Additionally, a 7.2 mg weekly dose of Wegovy is under study, which may offer enhanced weight loss benefits compared to the current highest dose.
Cardiovascular Benefits: Wegovy’s Proven Track Record
While both medications are approved for chronic weight management, Wegovy has the added benefit of being approved for reducing cardiovascular risk in adults with heart disease who are overweight or obese, as of March 2024. Wegovy’s long-term study showed a 20% reduction in major adverse cardiovascular events (MACE) such as heart attack, stroke, or cardiovascular death.
Age Approvals: Wegovy for Adolescents
Wegovy is approved for use in adults and adolescents aged 12 and older, making it one of only two such medications (the other being Saxenda, or liraglutide) for this age group. Zepbound, however, is currently approved only for adults, although studies are underway to explore its efficacy in adolescents.
Switching Between Medications and Combined Use
It is possible to switch from Wegovy to Zepbound if additional weight management support is needed. This typically involves starting at a lower dose of Zepbound and gradually increasing it. However, taking both medications simultaneously is not recommended; one will generally be prescribed in place of the other.
Cost Considerations and Savings
Both Zepbound and Wegovy are brand-name medications, but there are ways to save:
- Zepbound: With a manufacturer copay card, you could pay as little as $25 if you have commercial insurance coverage, or $550 for a 30-day supply if not covered.
- Wegovy: Eligible patients might pay as little as $0 with a copay card. Coverage varies by insurance plan, and while Medicare doesn’t cover weight-loss medications, Wegovy might be covered for its cardiovascular benefits in those with heart disease.
The Bottom Line
Zepbound (tirzepatide) and Wegovy (semaglutide) are injectable medications designed for chronic weight management, targeting appetite, hunger, and food cravings through similar but distinct mechanisms. Wegovy is approved for a broader age range and offers proven cardiovascular benefits, while Zepbound may lead to greater weight loss and may also have milder side effects. Your healthcare provider will consider your health history, age, and other factors to determine which medication might be the best fit for you.
