Head-to-Head, Side by Side
Zepbound vs Wegovy Comparison Chart: Every Number That Matters
In the SURMOUNT-5 head-to-head trial, Zepbound (tirzepatide) produced 20.2% average weight loss versus 13.7% for Wegovy (semaglutide) at 72 weeks. This zepbound vs wegovy comparison chart lines up the mechanisms, doses, cost, and FDA approvals for both drugs in one side-by-side table. Both are once-weekly subcutaneous injections for obesity, but they differ in how they work and how much weight people lose.
20.2%
Zepbound weight loss (SURMOUNT-5)
13.7%
Wegovy weight loss (SURMOUNT-5)
2
Receptors targeted by Zepbound (GIP + GLP-1)
1
Receptor targeted by Wegovy (GLP-1)
Key Takeaways
- Head-to-head winner on weight loss: In SURMOUNT-5, Zepbound averaged 20.2% body weight loss versus 13.7% for Wegovy at 72 weeks.
- Different mechanisms: Zepbound (tirzepatide) hits two receptors, GIP and GLP-1; Wegovy (semaglutide) hits one, GLP-1.
- Different extra indications: Zepbound is approved for obstructive sleep apnea; Wegovy is approved for cardiovascular risk reduction and for ages 12 and up.
- Cost edge: Zepbound's list price (~$1,086/month) sits below Wegovy's (~$1,350–$1,865/month), with LillyDirect self-pay vials from $299–$449/month.
- Side effects are nearly identical: both are mostly mild-to-moderate gastrointestinal effects, and both carry the same thyroid C-cell tumor boxed warning.
- Pick with your prescriber: the right choice depends on your indications, insurance, and how you tolerate each drug, not the headline number alone.
The Zepbound vs Wegovy Comparison Chart (Side-by-Side)
| Category | Zepbound (tirzepatide) | Wegovy (semaglutide) |
|---|---|---|
| Active ingredient | Tirzepatide | Semaglutide |
| Drug class | Dual GIP + GLP-1 agonist | GLP-1 agonist (monoagonist) |
| FDA approval (obesity) | November 8, 2023 | June 4, 2021 |
| Additional approvals | Obstructive sleep apnea (December 2024) | Cardiovascular risk reduction; pediatric (age 12+) |
| Starting dose | 2.5 mg/week | 0.25 mg/week |
| Maximum dose | 15 mg/week | 2.4 mg/week maintenance (7.2 mg max) |
| Titration steps | 6 steps (every 4 weeks) | 5 steps (every 4 weeks) |
| Half-life | ~5 days | ~7 days |
| Avg weight loss, monotherapy trials | 20.9% at 72 weeks (SURMOUNT-1) | 14.9% at 68 weeks (STEP 1) |
| Avg weight loss, head-to-head (SURMOUNT-5) | 20.2% (~50 lbs avg) | 13.7% (~33 lbs avg) |
| ≥25% body weight loss rate (SURMOUNT-5) | 32% of participants | 16% of participants |
| List price (without insurance) | ~$1,086/month | ~$1,350–$1,865/month |
| Self-pay vial / savings program | LillyDirect: $299–$449/month | NovoCare program (see novonordisk.com) |
| Common side effects | Nausea, diarrhea, constipation, vomiting | Nausea, diarrhea, vomiting, constipation |
| Available formulations | KwikPen + single-dose vials | KwikPen only |
SURMOUNT-5 head-to-head data: Aronne LJ et al., N Engl J Med. 2025;393:26-36. doi:10.1056/NEJMoa2416394.
⚠️ Read the Numbers in Context
SURMOUNT-5 was funded by Eli Lilly, the maker of Zepbound. Independent replication is still pending. Both trial arms were titrated to the maximum doses approved at the time (Zepbound 15 mg, Wegovy 2.4 mg), so the chart reflects best-case dosing rather than typical real-world results.
Plan Your Dosing Schedule for Either Drug
Map out a week-by-week titration plan for tirzepatide or semaglutide with the free GLP3Planner calculators.
What the SURMOUNT-5 Head-to-Head Trial Actually Showed
SURMOUNT-5 is the only direct head-to-head randomized trial between Zepbound and Wegovy. Every other weight-loss figure you see compares the two drugs across separate studies with different patients, so this trial is the cleanest data we have. Here is the design behind the numbers in the chart. For the longer narrative, read our full Zepbound vs Wegovy comparison.
Trial Design
- 751 adults with obesity and no type 2 diabetes
- 72-week duration, double-blind, randomized controlled trial
- Both arms titrated to maximum tolerated dose (Zepbound up to 15 mg, Wegovy up to 2.4 mg)
- Published in the New England Journal of Medicine, 2025
Key Weight Loss Results
At 72 weeks, the Zepbound arm lost 20.2% of body weight on average versus 13.7% for the Wegovy arm. Converted to pounds, that is roughly 50 lbs versus 33 lbs for an average participant. The gap is widest at the top end: 32% of Zepbound patients lost 25% or more of their body weight, compared with 16% on Wegovy, twice the share at that threshold. Both drugs still produced clinically meaningful weight loss.
Important Caveat
Eli Lilly funded SURMOUNT-5, and independent replication is pending. Both arms reached maximum approved doses, which most people in everyday use may not. Real-world outcomes vary with tolerability, the dose you actually reach, diet, and exercise. Use the trial numbers as a ceiling, not a promise.
Watch: A Doctor Compares Zepbound and Wegovy
Dr. Christopher McGowan, a board-certified gastroenterologist and obesity medicine specialist, walks through how Zepbound (tirzepatide) and Wegovy (semaglutide) differ in mechanism and results.
Mechanism Difference: Why Tirzepatide May Outperform
Tirzepatide activates two receptors, GIP and GLP-1, while semaglutide activates only GLP-1. The GIP receptor engagement is thought to add to energy expenditure and fat metabolism beyond what GLP-1 activation does on its own. That extra action may help explain the larger weight loss seen with Zepbound in SURMOUNT-5, though the trial measured outcomes, not the exact biological cause.
For the cellular-level breakdown of how the dual agonist works, see how tirzepatide works.
Dosing Ladder Comparison
Both drugs are once-weekly subcutaneous injections that start low and step up every 4 weeks. The tables below show each titration ladder so you can compare them at a glance.
Zepbound Titration Schedule (Tirzepatide)
| Step | Weekly dose | Duration |
|---|---|---|
| Step 1 | 2.5 mg | 4 weeks |
| Step 2 | 5 mg | 4 weeks |
| Step 3 | 7.5 mg | 4 weeks |
| Step 4 | 10 mg | 4 weeks |
| Step 5 | 12.5 mg | 4 weeks |
| Step 6 | 15 mg | Maintenance |
Wegovy Titration Schedule (Semaglutide)
| Step | Weekly dose | Duration |
|---|---|---|
| Step 1 | 0.25 mg | 4 weeks |
| Step 2 | 0.5 mg | 4 weeks |
| Step 3 | 1.0 mg | 4 weeks |
| Step 4 | 1.7 mg | 4 weeks |
| Step 5 | 2.4 mg | Maintenance |
One practical difference: Zepbound reaches its maximum dose in 16 weeks (six 4-week steps less the final maintenance phase) while Wegovy has one more step. This is a scheduling distinction, not a quality difference. For a printable reference, see the tirzepatide dosage chart, or plan your own schedule with the tirzepatide calculator.
FDA Approvals and Eligible Patients
Both drugs are approved for chronic weight management, but their extra indications differ enough to tip a decision. Someone with obstructive sleep apnea may lean toward Zepbound, while someone with established cardiovascular disease may lean toward Wegovy.
Who Zepbound Is Approved For
- Adults with obesity (BMI 30 or higher) or overweight (BMI 27 or higher) with a weight-related health condition, approved November 2023
- Obstructive sleep apnea in adults with obesity, approved December 2024 (the first drug approved for this use)
- Not approved for patients under 18 as of June 2026
Who Wegovy Is Approved For
- Adults and children aged 12 and older with obesity or overweight plus a related condition, approved 2021 for adults and 2023 for adolescents
- Cardiovascular risk reduction in adults with established cardiovascular disease and a BMI of 27 or higher, based on the SELECT trial (2024)
- Wegovy is the only one of the two approved for pediatric patients
Cost Comparison
List prices below are before insurance. Out-of-pocket cost depends heavily on your plan and any manufacturer programs, so treat these as starting points and confirm with your insurer.
| Cost factor | Zepbound | Wegovy |
|---|---|---|
| List price (without insurance) | ~$1,086/month | ~$1,350–$1,865/month |
| With insurance coverage | Varies; many commercial plans now cover weight-loss use | Varies; the SELECT indication may help coverage for CVD patients |
| Self-pay vials | $299 (2.5 mg), $399 (5 mg), $449 (7.5–15 mg) via LillyDirect | No equivalent manufacturer-direct vial program |
| Manufacturer savings program | Lilly savings card (zepbound.lilly.com/savings) | NovoCare program (novonordisk.com) |
For the full Zepbound pricing breakdown, including insurance scenarios, see our Zepbound cost guide.
Side Effects: What to Expect With Each Drug
Both medications share a nearly identical side effect profile that is gastrointestinal, dose-dependent, and usually mild to moderate. SURMOUNT-5 confirmed no clinically meaningful difference in GI side effect rates between the two arms.
Common Side Effects (Both Drugs)
The most common effects are nausea, diarrhea, constipation, and vomiting. They tend to peak during dose increases and ease as your body adjusts, so a slow titration generally reduces how often they occur.
Serious Warnings (Both Drugs)
Both drugs carry a boxed warning for thyroid C-cell tumors seen in rodent studies, with unknown human risk. Both are contraindicated in anyone with a personal or family history of medullary thyroid carcinoma or MEN 2. Talk to your prescribing physician about your individual risk before starting either medication.
For the full Zepbound safety breakdown, see our Zepbound side effects guide.
Which Should You Choose? A Decision Framework
This is a conversation to have with your prescriber, not a self-diagnosis. These are the practical factors that usually shape the choice.
- Lean toward Zepbound if the SURMOUNT-5 efficacy data is your top priority, or if you have obstructive sleep apnea (an approved Zepbound indication).
- Consider Wegovy if you are under 18, you have established cardiovascular disease where the SELECT data applies, or your insurance covers Wegovy but not Zepbound.
- Both drugs require a valid prescription, adherence to the titration schedule, and lifestyle changes (diet and exercise) for the best results.
For a deeper molecule-level comparison, see tirzepatide vs semaglutide, or compare the dose-stratified outcomes in Zepbound weight loss results.
Frequently Asked Questions
What is the biggest difference between Zepbound and Wegovy?
Zepbound (tirzepatide) activates two receptors, GIP and GLP-1, while Wegovy (semaglutide) activates only GLP-1. In the SURMOUNT-5 head-to-head trial, Zepbound produced 20.2% average weight loss versus 13.7% for Wegovy at 72 weeks. Both are once-weekly subcutaneous injections.
Which is stronger, tirzepatide or Wegovy?
In SURMOUNT-5 (751 participants, 72 weeks), tirzepatide at maximum tolerated dose produced greater average weight loss than semaglutide, 20.2% versus 13.7%. About 32% of Zepbound patients lost 25% or more of their body weight versus 16% on Wegovy. Both still produced clinically meaningful results.
Is Zepbound or Wegovy safer?
Both have similar gastrointestinal side effect profiles (nausea, diarrhea, constipation, vomiting) that are generally mild to moderate. SURMOUNT-5 found no clinically meaningful difference in adverse events between arms. Both carry identical boxed warnings for thyroid C-cell tumors. Individual safety depends on your medical history, so discuss it with your physician.
What is 1.7 mg Wegovy equivalent to in Zepbound?
No validated dose equivalence exists between semaglutide and tirzepatide because they target different receptors. Standard clinical guidance is to start Zepbound at 2.5 mg once weekly regardless of any prior Wegovy dose, then titrate on the normal schedule. Any switch should be supervised by your prescriber.
Which costs less, Zepbound or Wegovy?
At list price, Zepbound (~$1,086/month) is generally lower than Wegovy (~$1,350–$1,865/month). Zepbound also offers single-dose vials through LillyDirect at $299–$449/month for eligible self-pay patients. Insurance coverage and savings programs vary, so confirm your actual cost with your insurer and the manufacturer portals.
Can you take Zepbound and Wegovy at the same time?
No. These medications should never be combined. Both act on overlapping GLP-1 receptor pathways, so using them together would sharply raise the risk of severe gastrointestinal side effects and dangerous dehydration. Only one GLP-1 or GIP medication should be used at a time, under medical supervision.
Why are people switching from Wegovy to Zepbound?
Common reasons include the greater weight loss seen in SURMOUNT-5 (20.2% versus 13.7%), insurance formulary changes, and a lower list price on the Zepbound KwikPen. Switching requires a new prescription and restarting titration at 2.5 mg, since there is no direct dose conversion between the two drugs.
Plan Whichever Drug You Choose
Map out a week-by-week titration plan for either medication with the free GLP3Planner calculators.
References
- Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). N Engl J Med. 2025;393:26-36. doi:10.1056/NEJMoa2416394
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216.
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.
- U.S. Food and Drug Administration. FDA Approves New Treatments for Adults with Obesity or Overweight (Zepbound). November 8, 2023.
- U.S. Food and Drug Administration. FDA Approves New Drug Treatment for Chronic Weight Management (Wegovy). June 4, 2021.
- U.S. Food and Drug Administration. FDA Approves First Drug Treatment for Obstructive Sleep Apnea. December 20, 2024.
- Zepbound (tirzepatide) Prescribing Information. Eli Lilly and Company. 2023. FDA NDA 217806.
- Wegovy (semaglutide) Prescribing Information. Novo Nordisk. 2021. FDA NDA 215256.
Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare provider before starting, changing, or stopping any medication. Individual results vary, and neither Zepbound nor Wegovy should be used without proper medical supervision.
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