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How do Zepbound and Wegovy compare?

Medically reviewed by Kristianne Hannemann, PharmD. Last updated on May 24, 2024.

Official answer

by Drugs.com

Key Points

  • Zepbound and Wegovy are two FDA-approved weight loss medications. Zepbound is only approved in adults that meet certain criteria, while Wegovy can be used in certain people ages 12 and older.
  • Both Zepbound and Wegovy need to be titrated up to a maintenance dose. However, the maintenance dose may be reached faster with Zepbound than with Wegovy.
  • Side effects of Zepbound and Wegovy are similar, but Wegovy might cause more headaches.
  • Research is ongoing to determine whether patients lose more weight with Zepbound or Wegovy. In clinical trials, adults taking Zepbound lost more weight compared to adults who took Wegovy in separate studies.

Zepbound and Wegovy have different FDA-approved uses

Both Zepbound and Wegovy are newer weight loss medications, but they have some differences when it comes to who can use them.

Zepbound was approved by the FDA in 2023 for use in addition to a reduced-calorie diet and increased exercise in adults with a body mass index (BMI) of:

  • 30 kg/m2 or greater, or
  • 27 kg/m2 or greater in the presence of at least one weight-related condition (e.g., hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, cardiovascular disease)

Zepbound is currently not approved for use in children or adolescents. It also should not be used in adults with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2.

Wegovy was initially FDA approved in 2021 to reduce body weight in adults identified as overweight with at least one weight-related health condition. In 2022, it gained approval for weight reduction in people as young as 12 years old identified as obese. Recently, the FDA approved another indication in 2024: to lower the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and identified as either obese or overweight.

Similar to Zepbound, Wegovy should not be used in adults with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2.

Zepbound and Wegovy work slightly differently

Zepbound and Wegovy are designed to mimic incretins, which are hormones in the gut that help with digestion and blood sugar regulation. Two incretins are glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). Researchers believe these hormones play a role in controlling our appetite, which affects how much we eat. GLP-1 is known to suppress appetite and slow gastric emptying, which helps us feel fuller longer. GIP also makes us feel full by acting in a part of our brain called the hypothalamus.

One big difference between Zepbound and Wegovy is that Zepbound is a GIP receptor and GLP-1 receptor agonist whereas Wegovy is only a GLP-1 receptor agonist. This means they activate receptors (signaling proteins) in the brain that natural GIP and GLP-1 turn on. This leads to being less hungry and eating less, which promotes weight loss. Zepbound targets both of these pathways while Wegovy only targets one.

Zepbound and Wegovy are dosed differently

Another difference between Zepbound and Wegovy is how they are dosed. Both medications are injected under the skin once weekly. However, how much you inject each week will be different depending on which medication you are taking. The dose of Zepbound and Wegovy is slowly raised every few weeks to lower the risk of stomach side effects.

Zepbound dosing

Zepbound comes as pre-filled, single-dose pens or vials in multiple different strengths. The recommended dosage is the following:

  • Weeks 1-4: Inject 2.5 mg under the skin once weekly
  • Weeks 5-8: Inject 5 mg under the skin once weekly
  • Weeks 9 and thereafter: The dose may be increased by 2.5 mg, and again after at least 4 weeks on the current dose

The recommended maintenance dose of Zepbound is 5 mg, 10 mg, or 15 mg once a week.

Wegovy dosing

Wegovy comes as pre-filled, single-dose pens in five different strengths. The recommended dosage is the following:

Adults

  • Weeks 1-4: Inject 0.25 mg under the skin once weekly
  • Weeks 5-8: Inject 0.5 mg under the skin once weekly
  • Weeks 9-12: Inject 1 mg under the skin once weekly
  • Weeks 13-16: Inject 1.7 mg under the skin once weekly
  • Weeks 17 and onward: Inject 1.7 mg or 2.4 mg under the skin once weekly

The recommended maintenance dose of Wegovy in adults is 1.7 mg or 2.4 mg once a week. This will depend on how well you tolerate the medication.

Children 12 years and older

  • Weeks 1-4: Inject 0.25 mg under the skin once weekly
  • Weeks 5-8: Inject 0.5 mg under the skin once weekly
  • Weeks 9-12: Inject 1 mg under the skin once weekly
  • Weeks 13-16: Inject 1.7 mg under the skin once weekly
  • Week 17 and onward: Inject 2.4 mg under the skin once weekly

The recommended maintenance dose of Wegovy in children 12 years and older is 2.4 mg once a week. If 2.4 mg isn’t tolerated, the dose may be lowered to 1.7 mg once a week.

Related questions

Wegovy is more forgiving towards missed doses

If you miss a dose of Zepbound or Wegovy, what you should do may depend on how many days it has been or how many days are left until your next injection.

For Zepbound, you can give the injection right away if it has been 4 days or less since you have missed your dose. If it has been more than 4 days, you will need to skip that dose altogether and give your injection on the next regularly-scheduled day. In either case, continue with a once-weekly dosing schedule.

For Wegovy, you can take your missed dose as long as there are 2 days or more until your next scheduled dose. If your next dose is less than 48 hours away, you should skip the missed dose and continue with your usual dosing schedule.

Zepbound might cause more weight loss than Wegovy

Studies are ongoing comparing newer weight loss medications, including Zepbound and Wegovy. Based on clinical trial data, Zepbound may result in more weight loss in adults compared to adults taking Wegovy. However, more research is needed.

Zepbound clinical trials

Zepbound was studied during two clinical trials that lasted 72 weeks: SURMONT-1 and SURMONT-2. In total, 2,519 patients received either 5 mg, 10 mg or 15 mg of Zepbound once a week and 958 patients received once-weekly placebo injections.

  • Study 1 (SURMONT-1): Patients taking 5 mg, 10 mg, and 15 mg lost 15%, 19.5%, and 20.9% of their body weight at week 72, respectively. This was compared to a 3.1% reduction in body weight in the placebo group. On average, people taking the 15 mg dose lost 23.6 kg or 52 lbs.
  • Study 2 (SURMONT-2): Patients taking 10 mg or 15 mg lost 12.8% and 14.7% of their body weight, respectively. This was compared to a 3.2% reduction in body weight in the placebo group.

Wegovy clinical trials

Weight loss from Wegovy in adults was studied in five 68-week clinical trials. In the largest study, patients taking Wegovy lost 14.9% of their starting body weight at week 68 compared to a 2.4% reduction in the placebo group. The average weight loss in adults taking Wegovy was 15.3 kg or about 34 lbs.

Wegovy was also studied in a 68-week clinical trial in children 12 years and older with obesity. In this study, children taking Wegovy saw a 16.1% reduction in their starting body weight. This was compared to a 0.6% increase in weight in the placebo group.

Zepbound and Wegovy have similar side effects

Stomach side effects are common from both Zepbound and Wegovy, including nausea, diarrhea, and stomach pain. There aren’t studies directly comparing Zepbound and Wegovy, so it is hard to know which one is better tolerated. However, headache seems to be more common from taking Wegovy than Zepbound.

In clinical studies of Zepbound, the most common side effects reported in adults were:

  • Nausea (up to 28%)
  • Diarrhea (up to 23%)
  • Vomiting (up to 13%)
  • Constipation (up to 11%)
  • Stomach pain (up to 10%)
  • Indigestion (up to 10%)

Other side effects include injection site reactions, feeling tired, burping, and hair loss.

Common side effects reported by adults who took 2.4 mg of Wegovy during clinical trials include:

  • Nausea (44%)
  • Diarrhea (30%)
  • Vomiting (24%)
  • Constipation (24%)
  • Stomach pain (20%)
  • Headache (14%)
  • Feeling tired (11%)

Other side effects reported by adults were indigestion, dizziness, bloating, burping, and hair loss.

Children 12 years and older taking 2.4 mg of Wegovy reported similar side effects, including:

  • Nausea (42%)
  • Vomiting (36%)
  • Diarrhea (22%)
  • Headache (17%)
  • Stomach pain (15%)
  • Common cold (12%)

These are not all side effects reported by people taking Zepbound or Wegovy during studies. For more information, talk to your healthcare provider.

References

Jastreboff A.M., et. al. (2022). SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. In: The New England Journal of Medicine. Accessed 05/23/2024. Available from: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

Wegovy (semaglutide) prescribing information. (Updated March 2024). Novo Nordisk. Accessed 05/23/2024. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b

Wilding, J. P., et. al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. In: The New England Journal of Medicine. Accessed 05/23/2024. Available from: https://pubmed.ncbi.nlm.nih.gov/33567185/

Wook, K., et. al. (2009). The Role of Incretins in Glucose Homeostasis and Diabetes Treatment. In: Pharmacological Reviews. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2696340/

Zaffina, I., et. al. (2023). Effect of dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist on weight loss in subjects with obesity. In: Frontiers in Endocrinology. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9992880/

Zepbound (tirzepatide) prescribing information. (Updated March 2024). Eli Lilly and Company. Accessed 05/23/2024. Available from: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b

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