Retatrutide vs Wegovy vs Zepbound: Which Leads on Weight Loss?

Retatrutide (investigational), semaglutide (Wegovy), and tirzepatide (Zepbound) are three of the most discussed names in modern weight management. They are powerful tools that can help with substantial weight loss when used with healthy habits. But they are not the same. They differ in how they work, how much weight people tend to lose, side effects, cost, and how you can get them.

This guide explains those differences in clear language. It also gives you practical tips to talk with your healthcare provider and decide which option may fit your goals and health history.

Key takeaways

• Most weight loss seen in trials so far: Retatrutide 12 mg reached about 24.2% mean weight loss at 48 weeks in a Phase 2 trial. Retatrutide is not yet FDA‑approved and is only available in clinical studies.
• Top approved option today: Zepbound (tirzepatide) produced around 15–21% average weight loss at 72 weeks across doses in SURMOUNT‑1. Wegovy (semaglutide) produced about 15% at 68 weeks in STEP 1.
• How they differ: Retatrutide targets three hormone receptors (GLP‑1, GIP, and glucagon). Zepbound targets two (GLP‑1 and GIP). Wegovy targets one (GLP‑1). These differences likely help explain the weight‑loss results.
• Access: Retatrutide is available only in clinical trials. Wegovy and Zepbound are FDA‑approved and require a prescription. Do not use unregulated sources.

How these medicines work (in simple terms)

Your gut makes hormones after you eat that help control appetite, blood sugar, and how your body uses energy. These medicines act like those hormones:

• Wegovy (semaglutide) targets the GLP‑1 receptor. This helps you feel full sooner, slows down your stomach emptying, and can reduce cravings. Many people naturally eat fewer calories.
• Zepbound (tirzepatide) targets GLP‑1 and GIP receptors. In addition to the GLP‑1 effects above, GIP helps your body respond better to insulin after meals. The combination can boost weight loss for some people.
• Retatrutide targets GLP‑1, GIP, and glucagon receptors. Like the others, it can reduce appetite and improve blood sugar. The glucagon part may also increase energy use, which could add to weight loss. Retatrutide is still being studied.

In short: all three help you eat less and manage blood sugar better. Retatrutide and Zepbound engage more than one pathway, which may help explain the larger average weight loss seen in trials.

Efficacy: what the trials show

The table below summarizes key trial results. These numbers are averages across many people; individual results can vary.

Medication	Pivotal/Key trial	Duration	Mean weight loss	Dose(s) tested
Retatrutide (investigational)	NEJM Phase 2 (obesity, no diabetes)	48 weeks	~24.2% (12 mg)	1, 4, 8, 12 mg
Wegovy (semaglutide)	STEP 1	68 weeks	~15% (2.4 mg)	Up‑titrated to 2.4 mg
Zepbound (tirzepatide)	SURMOUNT‑1	72 weeks	~15–21% (5–15 mg)	5, 10, 15 mg

Notes:

• Retatrutide’s results are from a Phase 2 study. Larger Phase 3 studies are needed to confirm efficacy and safety before any FDA decision.
• Higher doses often produced more weight loss when people could tolerate the dose increases.
• Lifestyle support (nutrition, activity, sleep) helps improve and maintain results across all medicines.

What does “mean weight loss” mean?

“Mean” means average. If the mean weight loss is 20%, that means the typical person in the trial lost 20% of their starting body weight. Some people lost less, and some lost more.

Safety and side effects: what to expect and how to manage

All three medicines share similar, mostly gastrointestinal (GI) side effects. These are most common when you are increasing the dose and usually fade as your body adjusts.

• Common side effects: nausea, vomiting, diarrhea, constipation, stomach discomfort, and sometimes fatigue.
• Less common but important: gallbladder issues, rare pancreatitis, and a risk warning for people with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN2).
• Retatrutide‑specific note: heart rate increases were seen in a dose‑dependent way in Phase 2. Longer studies will clarify the long‑term significance.

Tips to reduce side effects

• Follow the titration schedule your clinician provides. Slower increases often mean fewer side effects.
• Eat smaller, balanced meals and avoid heavy, high‑fat meals during dose changes.
• Sip fluids and consider electrolyte drinks if you have vomiting or diarrhea.
• Pause dose increases if side effects are strong; call your clinic for guidance.

Always report severe symptoms (such as intense stomach pain) right away.

Dosing and how they are taken

All three are once‑weekly injections under the skin (subcutaneous). Approved products use prefilled pen devices designed for home use after training from your care team.

• Wegovy: Titrated up to 2.4 mg once weekly.
• Zepbound: 5, 10, or 15 mg once weekly with stepwise increases.
• Retatrutide: Doses from 1–12 mg were studied in Phase 2 with gradual titration. Devices and final doses will depend on future studies and any regulatory review.

If you are nervous about injections, ask your clinic to show you how to use the pen and practice with a demo device first.

Who might consider which option?

This is general information, not medical advice. Your clinician will recommend based on your health history, lab results, preferences, and coverage.

• You want the strongest approved option today: Zepbound’s results suggest higher average weight loss than Wegovy for many people, especially at higher doses.
• You want an established GLP‑1 option with broad use: Wegovy is widely used and studied. Some people tolerate it well and achieve meaningful results.
• You are interested in next‑generation options: Retatrutide is very promising but still investigational. You would need to qualify for a clinical trial.

Other factors matter too: existing conditions (like heart disease), medicines you already take, whether you have type 2 diabetes or prediabetes, and personal goals (such as improving sleep apnea, joint pain, or blood pressure).

Cost and coverage (what to expect)

Prices change over time and vary by location. Your out‑of‑pocket cost depends on insurance. Manufacturers often have support programs that may reduce copays for eligible patients.

• Wegovy: Often listed around ~$1,300+ per month without insurance. Savings programs can help.
• Zepbound: Often in a similar range (~$1,000+ per month) depending on pharmacy and coverage.
• Retatrutide: No retail price. In clinical trials, study drug is typically provided without charge, but coverage of visits and tests can vary.

Tips to navigate coverage

• Call your insurer to ask if the medicine is on formulary (the covered drug list) and what the prior authorization requirements are.
• Ask your clinic if they can send supporting documentation (BMI, comorbidities, failed weight‑loss attempts) to meet insurer rules.
• Check the manufacturer’s website for savings cards or patient assistance.
• If coverage is denied, ask your clinician about an appeal and whether another option may be easier to access.

How to combine with lifestyle changes (and why it matters)

These medicines work best when you also adopt steady, manageable habits:

• Nutrition: Focus on protein, vegetables, whole grains, and fiber. Smaller portions are often easier once you feel fuller on treatment.
• Activity: Walking, resistance training, and everyday movement help preserve muscle and maintain weight loss.
• Sleep and stress: Aim for consistent sleep and stress‑reduction routines to support appetite and energy.
• Follow‑up: Regular visits help you adjust doses, manage side effects, and celebrate progress.

Small changes made consistently beat extreme changes you cannot sustain.

Access and legality

• Retatrutide: Only available in legitimate clinical trials at this time. Check ClinicalTrials.gov to find studies and see if you qualify.
• Wegovy and Zepbound: FDA‑approved prescription medicines. Get them through licensed clinicians and pharmacies. Avoid unregulated online sellers and compounded versions that are not FDA‑approved.

Using unregulated sources can be unsafe and may be illegal.

Comparing beyond the headline number

Weight loss is important, but not the only outcome. You and your clinician may consider:

• Blood sugar: These medicines can improve HbA1c and fasting glucose, especially in people with diabetes or prediabetes.
• Blood pressure and cholesterol: Many people see improvements that may reduce long‑term cardiovascular risk.
• Liver health: Studies have shown reductions in liver fat in some patients.
• Quality of life: More energy, less joint pain, better sleep, and greater mobility can be major wins.

Ask how your care team will measure success beyond the scale.

Risks, warnings, and who should not take them

These medicines are not right for everyone. Talk to your clinician if you have:

• A personal or family history of medullary thyroid carcinoma (MTC) or MEN2
• A history of pancreatitis
• Severe gastrointestinal disease
• Pregnancy or plan to become pregnant
• Gallbladder disease

Your clinician will review your medications to check for interactions and decide whether to start, switch, or stop therapy.

What starting looks like (a typical journey)

1. Clinic visit: Review history, discuss goals, and check labs.
2. Start low: Begin with a low dose to reduce side effects.
3. Titration: Increase the dose every few weeks as tolerated.
4. Check‑ins: Share how you feel, any side effects, and progress.
5. Maintenance: Stay at the dose that balances results with tolerability.
6. Long‑term plan: Keep up healthy habits and revisit goals at regular intervals.

Frequently asked questions (FAQs)

Is retatrutide better than Wegovy or Zepbound?

Phase 2 results suggest retatrutide may lead to greater average weight loss, but it is still investigational. It is not approved and not available outside trials.

Can I switch between Wegovy and Zepbound?

Yes, sometimes. Switching should be done with medical oversight. Your clinician will time the change, select the starting dose, and monitor you closely.

Do these medicines work without diet and exercise changes?

You may still lose weight, but results are usually better and easier to maintain with healthy habits.

Will I regain weight if I stop?

Weight regain can happen after stopping any of these medicines. Planning for long‑term maintenance—whether medication, habits, or both—helps protect your progress.

What side effects should make me seek urgent care?

Severe stomach pain, signs of pancreatitis (such as intense pain that may spread to the back), or signs of gallbladder issues. Seek help immediately if you experience these.

Can I drink alcohol on these medicines?

Moderation is key. Alcohol can worsen nausea and may affect blood sugar.

Are these medicines addictive?

They are not considered addictive. They change hormone signaling related to appetite and metabolism.

Do they affect fertility or pregnancy?

You should not use these medicines during pregnancy. Discuss family planning with your clinician.

How fast will I see results?

Some people notice appetite changes in the first few weeks. Larger weight changes tend to appear over months.

Can teens use these medicines?

Wegovy has certain pediatric indications. Ask your clinician about age‑specific approvals and guidance.

What if I plateau?

Plateaus are common. Check on dose, diet quality, activity, sleep, and stress. Small adjustments can restart progress.

Is compounded semaglutide or tirzepatide safe?

Use only FDA‑approved products from licensed pharmacies. Compounded versions may not meet FDA standards, and safety cannot be guaranteed.

How do I choose between Wegovy and Zepbound?

Discuss your goals, side‑effect history, insurance coverage, and other conditions. Many people start with what is covered and well‑tolerated.

Can these medicines help conditions like sleep apnea or fatty liver?

Weight loss can improve many conditions, including sleep apnea and fatty liver disease. Your clinician may track those outcomes over time.

Plain‑language glossary

• GLP‑1 (glucagon‑like peptide‑1): A hormone that helps you feel full and supports blood sugar control.
• GIP (glucose‑dependent insulinotropic polypeptide): A hormone that helps your body release insulin after eating.
• Glucagon: A hormone that raises blood sugar; when targeted in a specific way, it may also increase energy use.
• Titration: Slowly increasing the dose over time to improve tolerability.
• MEN2: A rare condition that increases the risk of certain tumors, including medullary thyroid cancer.

How to talk to your clinician

Bring this short checklist to your appointment:

• Your goals (for example, percent weight loss, improving sleep apnea, lowering HbA1c)
• Past experiences with weight‑loss medicines and any side effects
• Current medications and supplements
• Any personal or family history of thyroid cancer or pancreatitis
• Questions about coverage, dosing, and expected timelines

References

• NEJM Phase 2 retatrutide obesity study (2023): https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
• STEP 1 semaglutide (Wegovy) obesity trial (NEJM 2021): https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
• SURMOUNT‑1 tirzepatide (Zepbound) obesity trial (NEJM 2022): https://www.nejm.org/doi/full/10.1056/NEJMoa2206038
• FDA drug information: https://www.fda.gov/drugs
• ClinicalTrials.gov (trial search): https://clinicaltrials.gov/