People often ask which of the three headline medicines delivers the best weight loss: tirzepatide (sold as Mounjaro and Zepbound), semaglutide (Wegovy) or the investigational retatrutide. This article focuses on one thing only: Mounjaro vs Wegovy vs Retatrutide results as reported in published trials. We look at average loss, the share of people reaching key milestones, how long it took, side effects and what the numbers do and do not mean for you.
If you want a broader overview of price, access and product details, our companion article Mounjaro vs Wegovy vs Retatrutide covers that. Here we go deep on the data.
The Three Trials You Need to Know
Wegovy (semaglutide 2.4 mg): STEP 1
The STEP 1 trial enrolled adults with overweight or obesity without diabetes and followed them for 68 weeks. On semaglutide 2.4 mg weekly, average weight change was about minus 14.9%, compared with about minus 2.4% on placebo. About 86% lost at least 5%, around 69% lost at least 10%, roughly half lost at least 15% and about a third lost at least 20%.
Mounjaro and Zepbound (tirzepatide): SURMOUNT-1
The SURMOUNT-1 trial lasted 72 weeks. Average weight loss was about 15.0% at 5 mg, 19.5% at 10 mg and 20.9% at 15 mg, versus about 3.1% on placebo. At the highest dose, over 90% of people lost at least 5% of weight and more than half lost at least 20%.
Retatrutide: phase 2 obesity trial
In the retatrutide phase 2 trial, participants received weekly doses for 48 weeks. At 12 mg, average weight loss was about 24.2%, compared with about 2.1% on placebo. At lower doses, losses were smaller, such as about 16.3% at 4 mg. Phase 3 trials are ongoing, and the compound is not FDA approved.
Results at a Glance
| Medicine (study) | Duration | Average loss at top studied dose | Placebo |
|---|---|---|---|
| Wegovy / semaglutide 2.4 mg (STEP 1) | 68 weeks | About 14.9% | About 2.4% |
| Mounjaro, Zepbound / tirzepatide 15 mg (SURMOUNT-1) | 72 weeks | About 20.9% | About 3.1% |
| Retatrutide 12 mg (phase 2) | 48 weeks | About 24.2% | About 2.1% |
The pattern is clear: moving from a single hormone target (semaglutide) to two (tirzepatide) to three (retatrutide) has gone hand in hand with larger average results.
Head-to-Head: Tirzepatide vs Semaglutide
Cross-trial comparisons can mislead because populations and designs differ. A direct comparison is stronger evidence. In the SURMOUNT-5 trial, tirzepatide was compared with semaglutide in adults with obesity over 72 weeks, and tirzepatide produced a larger average weight reduction, roughly 20% compared with about 14%. That aligns with what the separate trials suggested. For the practical differences, read our semaglutide vs tirzepatide guide.
There is no head-to-head trial of retatrutide against the other two in obesity yet, so any ranking against them is provisional.
How Fast Do Results Arrive?
In all three programs, weight loss was steepest in the first six to nine months and then flattened. Tirzepatide and semaglutide were titrated up over 16 to 20 weeks, which is why early results are modest before accelerating. Retatrutide’s phase 2 trial showed a continuing downward trajectory at 48 weeks without clear plateau at the higher doses, suggesting that longer studies may show even greater totals. This is one reason there is so much interest in the molecule.
People With Type 2 Diabetes Lose Less
Results in people with type 2 diabetes are lower than in people without it. For example, in the STEP 2 trial semaglutide 2.4 mg produced about 9.6% average loss over 68 weeks, and tirzepatide’s SURMOUNT-2 trial showed average losses of roughly 12 to 15% over 72 weeks. If you have diabetes, use diabetes-specific numbers when setting expectations.
Side Effects Compared
All three agents share gastrointestinal side effects such as nausea, diarrhea, vomiting and constipation, which are most noticeable during dose escalation.
- Wegovy: nausea affected about 44% of participants in STEP 1, with discontinuation for adverse events in around 7%.
- Mounjaro: nausea affected roughly a quarter to a third of participants depending on dose, with discontinuation for adverse events around 4 to 7%.
- Retatrutide: gastrointestinal effects were dose-dependent and more frequent at higher doses, with a heart rate increase and reports of altered skin sensation noted in early studies, and more discontinuations at the top dose.
Our detailed pages on Wegovy side effects and Mounjaro side effects explain management strategies, and the complete guide to weight loss peptide side effects covers all three.
What the Numbers Do Not Tell You
- They are averages. Some people lose far more, and some lose far less.
- Trials include coaching. Participants received lifestyle counseling and structured follow-up.
- Dose matters. Many people do not reach or stay on the top dose.
- Adherence matters. Real-world discontinuation is higher than in trials.
- Retatrutide is still being tested. Phase 2 results are promising but not final.
Which Result Matters for You?
Choose the medicine based on your health profile, goals, side effect tolerance and access, not the biggest number. Someone with heart disease may prefer semaglutide’s cardiovascular evidence. Someone needing larger weight reduction may be a better candidate for tirzepatide. Retatrutide deserves a careful conversation with a physician because it is investigational. Start by checking whether you meet clinical criteria in our guide on who qualifies for prescription weight loss medication.
You can then view the Wegovy, Mounjaro and retatrutide product pages, or ask our team which fits. At Weight Lose Solution, prescription treatments and peptide products are dispensed only after an online health questionnaire has been reviewed and approved by a licensed physician, based on your individual situation.
Milestone Comparison: How Many People Hit Each Target?
Averages are useful, but milestones describe how many people reach a meaningful goal. Approximate figures from the trials above, at the highest studied doses:
| Milestone | Wegovy (STEP 1) | Mounjaro / Zepbound 15 mg (SURMOUNT-1) |
|---|---|---|
| At least 5% weight loss | About 86% | About 91% |
| At least 10% weight loss | About 69% | About 84% |
| At least 15% weight loss | About 51% | About 71% |
| At least 20% weight loss | About 32% | About 57% |
These percentages show why many clinicians consider tirzepatide the stronger option for people who need a large reduction, while semaglutide remains an effective and well-understood choice for many others. Retatrutide’s phase 2 data suggested that a majority of participants at the top dose lost more than 20% of body weight, but because this was a smaller, earlier trial the numbers should be treated cautiously.
Dose-Response: More Is Not Always Better for You
Every program showed that higher doses produced greater average loss, but they also showed more side effects. That is why clinicians usually titrate according to your response rather than racing to the highest dose. For tirzepatide, the 5 mg dose already produced about 15% average loss in SURMOUNT-1, which is as large as the average semaglutide 2.4 mg result. A person who does well on a mid-dose may not need to go higher. Learn how stepwise increases work in our Mounjaro dosing schedule.
Why Cross-Trial Comparisons Need Caution
When you line up percentages from different trials, remember that populations differ in age, starting weight, sex mix and diabetes status. Trial lengths vary from 48 to 72 weeks. Some trials allowed participants to reduce their dose when side effects were troublesome, and different methods are used to count participants who dropped out. Regulators therefore look for head-to-head trials and long-term follow-up. In short, treat the table as a guide to the order of magnitude, not as a precise promise of results.
Beyond Weight: Other Outcomes That Matter
Weight is only one outcome. Semaglutide 2.4 mg has demonstrated a reduction in major cardiovascular events in adults with established cardiovascular disease and overweight or obesity. Tirzepatide has shown improvements in blood pressure, triglycerides and blood sugar and has an approved use in obstructive sleep apnea in adults with obesity. Retatrutide has shown reductions in liver fat in early studies, which makes it of interest for fatty liver disease, but this remains under investigation. If you have heart disease, diabetes or sleep apnea, discuss these additional benefits with your doctor, because they can matter more than the final pounds lost.
What Happens When You Stop?
Results depend on staying on treatment. In the follow-up of STEP 1, participants who stopped semaglutide regained about two-thirds of the weight they had lost within a year. In SURMOUNT-4, people switched from tirzepatide to placebo regained a significant share of their weight while those who continued lost more. Retatrutide will likely follow a similar pattern. We explore this further in our article about stopping Wegovy, and our dedicated guide on what happens after you stop appears elsewhere in this series.
A Simple Decision Framework
- Confirm eligibility. BMI and health conditions come first, as covered in our eligibility guide.
- Define your target. If you need 10 to 15% loss, semaglutide or lower-dose tirzepatide may suffice. If you need 20% or more, tirzepatide may be a better fit.
- Review your health profile. Heart disease, kidney disease, diabetes and medications all shape the choice.
- Check tolerability and history. Previous reactions to GLP-1 medicines should guide dose and product.
- Be realistic about investigational options. Retatrutide may be exciting, but it lacks full safety data and approval.
- Plan for the long term. Consider cost, supply and maintenance before you start.
What Is Coming Next?
The field is moving quickly. Retatrutide is in phase 3 trials, amylin-based combinations such as cagrilintide with semaglutide have shown large reductions in late-stage studies, and oral options are in development. As more data arrive, rankings may change. We update our guides regularly, and you can see how the full landscape looks in our overview of the best peptides for weight loss in 2026.
Key Takeaways
- Average weight loss in trials: about 15% for Wegovy, up to about 21% for Mounjaro and Zepbound, and about 24% for retatrutide at the top phase 2 dose.
- Tirzepatide beat semaglutide in a direct head-to-head trial.
- Retatrutide is the most promising but remains investigational and is not FDA approved.
- All three cause similar digestive side effects, mostly during dose increases.
- Weight returns for many people after stopping, so plan for the long term.
Ready to take the next step? Browse our weight loss medications and peptides, or learn how our physician review works before you decide.
How to Use This Data in a Doctor Conversation
Bring the numbers with you. Ask your clinician which trial population looks most like you, what average loss is realistic at the dose you are likely to reach, how side effects will be monitored and when you will review progress. Ask what the plan is if you do not reach a 5% loss by around three months at a therapeutic dose, since that is a common checkpoint for deciding whether to change course. Good clinicians welcome these questions, and the answers will make your decision far more confident than comparing headline percentages alone.
Frequently Asked Questions
Which causes more weight loss: Mounjaro or Wegovy?
In published trials, tirzepatide (Mounjaro, Zepbound) produced larger average weight loss, up to about 20.9% in SURMOUNT-1, than semaglutide (Wegovy), about 14.9% in STEP 1. A head-to-head trial also favored tirzepatide.
How does retatrutide compare with Mounjaro and Wegovy?
Retatrutide produced an average of about 24% weight loss at the top dose in a phase 2 trial, higher than the others at similar stages, but it is investigational and not FDA approved.
Are these results guaranteed?
No. They are averages from clinical trials with lifestyle support. Individual results vary widely.
Which has the fewest side effects?
All have similar gastrointestinal side effects. Rates depend on dose and how quickly the dose is raised, and individual tolerance varies.
Medical disclaimer: this article is educational and does not replace personalized medical advice. Retatrutide is not FDA approved. Consult a licensed clinician before starting treatment.