Cross-Compound Comparison
Wegovy vs Zepbound: What the Data Shows
When comparing Wegovy vs Zepbound, the clearest evidence comes from SURMOUNT-5, the first randomized head-to-head trial of semaglutide and tirzepatide in adults with obesity. Participants on Zepbound lost an average of 20.2% of body weight versus 13.7% on Wegovy at 72 weeks. Both are FDA-approved once-weekly injections, but they differ in mechanism, dosing, half-life, and additional indications.
Key Takeaways
- SURMOUNT-5 head-to-head (2025): tirzepatide (Zepbound) produced 20.2% vs semaglutide (Wegovy) 13.7% weight loss at 72 weeks in adults with obesity. The trial was funded by Eli Lilly.
- Mechanism difference: Wegovy targets only GLP-1 receptors. Zepbound targets both GLP-1 and GIP receptors, a dual action that researchers believe may contribute to its higher average weight loss.
- Both are once-weekly injections, but Wegovy reaches maintenance dose in about 20 weeks (5 steps) and Zepbound in about 24 weeks (6 steps).
- Different additional indications: Wegovy has approval for cardiovascular risk reduction and for people aged 12 and older. Zepbound has approval for obstructive sleep apnea, the first drug to carry that indication.
- Insurance coverage and individual response often matter more than trial averages. Neither drug is the right choice for every person.
20.2%
Zepbound weight loss (SURMOUNT-5)
13.7%
Wegovy weight loss (SURMOUNT-5)
Both
FDA-approved for obesity
1x / week
Dosing frequency (both drugs)
Wegovy vs Zepbound: Quick Comparison
The table below covers the six most-searched dimensions of the wegovy vs zepbound comparison, sourced from FDA labels and the SURMOUNT-5 trial (NEJM, 2025).
| Dimension | Wegovy (semaglutide) | Zepbound (tirzepatide) |
|---|---|---|
| Mechanism | GLP-1 receptor agonist (monoagonist) | GLP-1 + GIP dual agonist |
| Dose range | 0.25 mg to 2.4 mg weekly (7.2 mg max) | 2.5 mg to 15 mg weekly |
| SURMOUNT-5 weight loss | 13.7% at 72 weeks | 20.2% at 72 weeks |
| FDA weight-loss approval | 2021 | 2023 |
| Half-life | ~7 days | ~5 days |
| Key extra indication | Cardiovascular risk reduction; approved age 12+ | Obstructive sleep apnea (first drug for this) |
*SURMOUNT-5 data: Jastreboff AM et al. N Engl J Med. 2025;392:1861-1874. DOI: 10.1056/NEJMoa2501082.
Funding note: SURMOUNT-5 was sponsored by Eli Lilly, the manufacturer of Zepbound (tirzepatide). Independent replication of these findings is pending. Both arms reached maximum approved doses; real-world users often plateau at lower doses.
How Wegovy and Zepbound Work Differently
Both drugs mimic gut hormones to reduce appetite and slow digestion, but they target different receptors. That single difference shapes their clinical profiles.
GLP-1: The Shared Mechanism
Both Wegovy and Zepbound activate the GLP-1 (glucagon-like peptide-1) receptor. GLP-1 activation signals the brain that you're full, slows gastric emptying so food exits the stomach more gradually, and improves insulin sensitivity. Both drugs produce these effects.
What the GIP Receptor Adds (Zepbound Only)
Zepbound also activates the GIP (glucose-dependent insulinotropic polypeptide) receptor. GIP receptors sit in fat tissue as well as the gut and pancreas. Researchers believe the GIP component enhances the GLP-1 effect and contributes to Zepbound's additional fat loss. The causal link is not confirmed in a mechanistic head-to-head study, but the association with higher weight loss in trials is consistent.
Left: Wegovy activates GLP-1 receptors only. Right: Zepbound activates both GLP-1 and GIP receptors.
Wegovy (semaglutide)
Monoagonist. Targets GLP-1 receptors only. Developed by Novo Nordisk. Half-life approximately 7 days, producing very stable weekly drug levels.
Zepbound (tirzepatide)
Dual agonist. Targets both GLP-1 and GIP receptors simultaneously. Developed by Eli Lilly. Half-life approximately 5 days, slightly more fluctuation between weekly doses than semaglutide.
Head-to-Head Weight Loss Results: SURMOUNT-5 (2025)
SURMOUNT-5, published in the New England Journal of Medicine in May 2025, is the first and only randomized controlled trial to directly compare tirzepatide and semaglutide in adults with obesity (no type 2 diabetes). The headline numbers: participants on tirzepatide lost an average of 20.2% of body weight and those on semaglutide lost 13.7%, both at 72 weeks. The absolute difference of 6.5 percentage points translates to roughly 17 additional pounds for an average participant.
SURMOUNT-5 (NEJM 2025): tirzepatide 20.2% vs semaglutide 13.7% body weight loss at 72 weeks. n=751 adults with obesity. Both arms at maximum approved dose.
Beyond Averages: Who Lost the Most Weight?
The responder analysis tells a sharper story. In the tirzepatide arm, 32% of participants lost 25% or more of their body weight, compared to 16% in the semaglutide arm. That means roughly 1 in 3 Zepbound users in this trial lost a quarter of their body weight over 72 weeks, compared to about 1 in 6 on Wegovy. For a person who starts at 240 pounds, a 25% loss is 60 pounds.
Comparing Across All Three Major Trials
Three pivotal trials inform this comparison. Only SURMOUNT-5 is a valid head-to-head. STEP 1 and SURMOUNT-1 used different populations and should not be directly compared.
| Trial | Drug | Duration | Weight Loss | Head-to-Head? |
|---|---|---|---|---|
| STEP 1 (2021) | Semaglutide 2.4mg | 68 weeks | 14.9% avg | No (single arm) |
| SURMOUNT-1 (2022) | Tirzepatide 15mg | 72 weeks | 20.9% max dose | No (single arm) |
| SURMOUNT-5 (2025) | Tirzepatide vs Semaglutide | 72 weeks | 20.2% vs 13.7% | Yes (n=751 obesity) |
STEP 1 and SURMOUNT-1 used different populations and designs. Do not use them as a substitute for SURMOUNT-5 when making direct comparisons. SURMOUNT-5 is the only valid head-to-head.
Dosing: How You Take Wegovy vs Zepbound
Both drugs are once-weekly subcutaneous injections, administered in the abdomen, thigh, or upper arm using auto-injector pens. The titration schedules differ in the number of steps and the dose ranges.
Titration Timeline Comparison
Wegovy (semaglutide)
| Step | Dose | Duration |
|---|---|---|
| Start | 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 |
| Maintenance | 2.4 mg | Ongoing |
Reaches maintenance in approx. 20 weeks
Zepbound (tirzepatide)
| Step | Dose | Duration |
|---|---|---|
| Start | 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 |
| Maintenance | 15 mg | Ongoing |
Reaches maintenance in approx. 24 weeks
Half-life and missed doses: Wegovy has a half-life of approximately 7 days, meaning drug levels remain quite stable between weekly injections and the drug takes about 4 to 5 weeks to reach steady state (the figure in the Ozempic label; the Wegovy label gives none). Zepbound has a half-life of approximately 5 days, producing slightly more fluctuation between weekly doses while reaching steady state in about 4 weeks (Zepbound label). For a missed dose, the longer half-life of Wegovy generally means a slightly longer window before levels drop significantly. The free GLP3Planner calculator models these pharmacokinetics for both drugs.
Track Your Dosing Schedule
GLP3Planner's free pharmacokinetic calculator visualizes drug levels over time for both Wegovy and Zepbound. See how your dose builds at each titration step.
Side Effects: Are They Different?
Both drugs share the same primary GI side-effect profile. The most commonly reported effects for both Wegovy and Zepbound are nausea, diarrhea, constipation, and vomiting. SURMOUNT-5 found the overall safety profiles were similar across both arms. Some data suggest Wegovy may cause slightly more nausea and constipation while Zepbound may cause slightly more injection-site reactions, but the differences are modest.
Side Effects by Drug
| Side Effect | Wegovy | Zepbound |
|---|---|---|
| Nausea | Common; mild to moderate | Common; mild to moderate |
| Diarrhea | Common | Common |
| Constipation | Common; slightly more reported vs Zepbound in some data | Common |
| Vomiting | Common; dose-dependent | Common; dose-dependent |
| Injection-site reactions | Less frequent | Slightly more frequent in some reports |
Serious Side Effects (Both Drugs)
- Pancreatitis (inflammation of the pancreas)
- Gallbladder disease (cholelithiasis, cholecystitis)
- Heart rate increase (tachycardia)
- Suicidal ideation and behavior (FDA labeling requirement)
Talk to your doctor before starting either medication. Stop use and seek care immediately if you experience severe abdominal pain, vision changes, or signs of allergic reaction.
Managing Side Effects
For both drugs, the same general strategies help reduce GI side effects:
- Stay at each titration step for the full 4 weeks before escalating
- Eat smaller meals and avoid high-fat or heavily processed foods
- Stay well hydrated throughout the day
- Time your injection on a consistent day each week
- Tell your doctor if side effects are significant; they can hold a dose increase
For more detail, see the Zepbound side effects guide and the Wegovy side effects guide.
FDA Approvals: Where Wegovy and Zepbound Differ
Both drugs share the core obesity indication (BMI 30 or higher, or BMI 27 or higher with a weight-related condition). Where they separate is in additional approvals that reflect their different trial histories.
Wegovy FDA Indications
- Chronic weight management (adults, 2021)
- Chronic weight management (ages 12+, 2023)
- Cardiovascular risk reduction in adults with obesity/overweight and existing heart disease (2024, SELECT trial)
Zepbound FDA Indications
- Chronic weight management (adults, 2023)
- Moderate-to-severe obstructive sleep apnea in adults with obesity (December 2024) -- the first drug ever approved for this indication
The cardiovascular indication for Wegovy is based on the SELECT trial (NEJM, 2023), which showed a 20% reduction in major adverse cardiovascular events in adults with obesity and existing heart disease. Zepbound does not carry this indication as of April 2026, though cardiovascular trials are ongoing.
For anyone between 12 and 17, Wegovy is the only FDA-approved option of the two. Zepbound is approved for adults only.
Cost and Insurance Coverage
Without insurance, both drugs typically cost over $1,000 per month. The exact price varies by pharmacy, savings program, and dosage strength. Checking with your pharmacy and manufacturer savings programs is the most accurate way to get a current number.
- Eli Lilly (Zepbound): offers a savings card program for commercially insured and uninsured patients. Check lilly.com for current terms.
- Novo Nordisk (Wegovy): offers a similar savings program for Wegovy. Check novocare.com for current terms.
- Insurance coverage varies significantly. For many people, whichever drug their insurer covers becomes the practical choice.
- Compounded versions are available from compounding pharmacies for both drugs, though regulatory status is subject to change. See separate guides on compounded tirzepatide and compounded semaglutide for more detail.
Pricing changes frequently. Verify current costs directly with your pharmacy or manufacturer savings programs before making a decision based on cost.
Which One Is Right for You?
Neither drug is the right choice for every person. Individual response, tolerability, other conditions, insurance coverage, and your doctor's read of your situation all shape the decision. The framework below covers the most common scenarios.
Consider Zepbound if:
- You want the highest average weight loss based on current trial data
- You have moderate-to-severe obstructive sleep apnea alongside obesity
- Your insurance covers tirzepatide
- Your doctor recommends it based on your full picture
Consider Wegovy if:
- You have a history of cardiovascular events (heart attack or stroke) -- SELECT trial data supports this indication
- You are between 12 and 17 years old (Wegovy is approved; Zepbound is not)
- You tried Zepbound and did not tolerate it
- Your insurance covers semaglutide
Important: This framework is for context only. Your doctor knows your full history; this article does not. Do not start, stop, or change any medication based on what you read here.
GLP3Planner Calculator: Track Your Wegovy or Zepbound Schedule
GLP3Planner is a free pharmacokinetic calculator that uses exponential decay modeling to visualize how your drug levels build and change over time. It supports both Wegovy and Zepbound. You can visualize dose accumulation across each titration step, understand what happens to levels if you miss a dose, and export or share your schedule.
Board-certified obesity medicine physician Christopher McGowan, MD covers mechanism, trial data, and how to think about choosing between tirzepatide (Zepbound) and semaglutide (Wegovy).
Visualize Your Dosing Schedule
Free calculator. No sign-up required. Works for both Wegovy (semaglutide) and Zepbound (tirzepatide).
Frequently Asked Questions
Is Zepbound more effective than Wegovy for weight loss?
In the SURMOUNT-5 trial, the first head-to-head study comparing the two drugs in adults with obesity, participants on Zepbound (tirzepatide) lost an average of 20.2% of their body weight versus 13.7% on Wegovy (semaglutide) over 72 weeks. This trial was funded by Eli Lilly, Zepbound's manufacturer. Individual results vary significantly.
What is the main difference between Wegovy and Zepbound?
Wegovy (semaglutide) targets only the GLP-1 receptor. Zepbound (tirzepatide) targets both the GLP-1 and GIP receptors, making it a dual agonist. This difference in mechanism is believed to contribute to Zepbound's higher average weight loss in clinical trials, though the exact mechanism has not been confirmed in a dedicated head-to-head mechanistic study.
Do Wegovy and Zepbound have different side effects?
Both drugs share a similar GI side-effect profile: nausea, diarrhea, constipation, and vomiting are the most common, and both are mostly mild to moderate and dose-dependent. SURMOUNT-5 found overall safety profiles were similar. Some reports suggest Wegovy may cause slightly more nausea and constipation, while Zepbound may cause slightly more injection-site reactions.
Why do people switch from Wegovy to Zepbound?
Common reasons include: plateauing weight loss on Wegovy, insurance coverage changes, the desire for higher efficacy based on SURMOUNT-5 data, or a doctor's recommendation. Some people also switch after learning about Zepbound's additional approval for obstructive sleep apnea, if that is a concurrent condition.
Is Zepbound approved for teenagers?
No. As of April 2026, Zepbound is approved for adults only. Wegovy (semaglutide) has FDA approval for chronic weight management in pediatric patients aged 12 and older, making it the appropriate choice when a medication is needed for a teenager.
Which has more FDA indications, Wegovy or Zepbound?
Both are FDA-approved for weight loss in adults. Wegovy additionally has approval to reduce cardiovascular risk in adults with obesity and existing heart disease, and for patients aged 12 and older. Zepbound additionally has approval for moderate-to-severe obstructive sleep apnea in adults with obesity, the first drug approved for that specific indication.
How long does it take to reach the full dose of Wegovy vs Zepbound?
Wegovy follows a 5-step titration from 0.25 mg to 2.4 mg, reaching maintenance dose in approximately 20 weeks. Zepbound follows a 6-step titration from 2.5 mg to 15 mg, reaching maintenance in approximately 24 weeks. Both increase dose every 4 weeks. GLP3Planner's free calculator can visualize either schedule.
How do Wegovy and Zepbound differ in half-life?
Wegovy (semaglutide) has a half-life of approximately 7 days. Zepbound (tirzepatide) has a half-life of approximately 5 days. The slightly shorter half-life of Zepbound means drug levels fluctuate a bit more between weekly doses compared to Wegovy, though both reach stable steady-state levels within weeks of consistent dosing: about 4 weeks for Zepbound and about 4 to 5 weeks for semaglutide (Ozempic label).
Can I use the GLP3Planner calculator for both Wegovy and Zepbound?
Yes. GLP3Planner supports both compounds. The calculator uses pharmacokinetic modeling to visualize your dose schedule, track active drug levels over time, and plan titration steps for both Wegovy (semaglutide) and Zepbound (tirzepatide). It is free and does not require an account.
What does the SURMOUNT-5 trial mean for choosing between Wegovy and Zepbound?
SURMOUNT-5 (NEJM, 2025) was the first randomized head-to-head trial comparing tirzepatide and semaglutide in adults with obesity. Tirzepatide showed 20.2% vs 13.7% weight loss at 72 weeks. However, the trial was funded by Eli Lilly, both arms used maximum approved doses, and individual response varies. The results are useful context to bring to your doctor.
Does Wegovy protect against heart attacks but Zepbound does not?
Wegovy (semaglutide) has FDA approval to reduce the risk of cardiovascular events including heart attack and stroke in adults with obesity or overweight who have established heart disease, based on the SELECT trial (NEJM, 2023). Zepbound does not carry this specific cardiovascular indication as of April 2026, though cardiovascular studies of tirzepatide are ongoing.
Are the dosing pens the same for Wegovy and Zepbound?
Both are subcutaneous (under-skin) injections delivered once weekly in the abdomen, thigh, or upper arm using auto-injector pens. The pens differ in design (Novo Nordisk for Wegovy, Eli Lilly for Zepbound) and the dose ranges differ significantly (Wegovy up to 7.2 mg, Zepbound up to 15 mg). Both are available as single-dose auto-injector pens.
References
- Jastreboff AM, Kushner RF, Deanfield J, et al. Tirzepatide Once Weekly for Obesity (SURMOUNT-5). N Engl J Med. 2025;392:1861-1874. DOI: 10.1056/NEJMoa2501082
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387:205-216. DOI: 10.1056/NEJMoa2206038
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384:989-1002. DOI: 10.1056/NEJMoa2032183
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389:2221-2232. DOI: 10.1056/NEJMoa2307563
- U.S. Food and Drug Administration. FDA Approves First Drug Treatment for Obstructive Sleep Apnea. FDA News Release. December 20, 2024. FDA.gov
Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice, diagnosis, or treatment recommendations. The information presented is based on published clinical trial data and FDA labeling as of April 2026. Always talk to a licensed doctor before starting, stopping, or changing any medication. Individual results vary. Neither Wegovy nor Zepbound should be used without appropriate medical supervision.
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