Semaglutide vs Tirzepatide

Ozempic and Wegovy vs Mounjaro and Zepbound: one GLP-1 drug and one dual GIP/GLP-1 drug

By MoveWell Research Team Updated November 1, 2026

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Which one for what

Tirzepatide led to more weight loss in the only head-to-head obesity trial; semaglutide has more approved uses and comes as a pill.

  • Weight loss: tirzepatide
  • Type 2 diabetes: no winner
  • Heart risk without diabetes: semaglutide
  • Sleep apnea: tirzepatide
  • Kidney disease or MASH: semaglutide
  • A pill: semaglutide

See all three side by side: Semaglutide vs Tirzepatide vs Retatrutide

Sequence diagram of semaglutide showing its 31 amino acids and the side chain at Lys26
SemaglutideGLP-1 agonist · 31 amino acidsSemaglutide guide
Diagram of tirzepatide's label-confirmed changes: Aib at positions 2 and 13, a C20 fatty diacid on Lys20 and a C-terminal amide
TirzepatideGIP + GLP-1 · label changes only; letters not shownTirzepatide guide
In this guide
  1. Verdict
  2. At a glance
  3. Evidence by goal
  4. Head-to-head trials
  5. Side effects
  6. Key differences
  7. Can you use both?
  8. Where to get each
  9. FAQ
  10. References

At a glance

SemaglutideTirzepatide
What it isGLP-1 receptor agonist. A modified GLP-1 peptide with a fatty acid chain that binds albumin1GIP and GLP-1 receptor agonist. A peptide based on the GIP sequence, with a fatty diacid that binds albumin2
StatusFDA-approved as three brands (Ozempic, Wegovy and Rybelsus), as weekly injections and daily tablets1, 3, 4, 5FDA-approved: Mounjaro (May 13, 2022) and Zepbound (November 8, 2023)6, 7
Evidence5/5FDA-approved, with large outcome trials5/5FDA-approved, with large outcome trials
Dosing frequencyWeekly injection (Ozempic, Wegovy, Wegovy HD) or daily tablet (Rybelsus, Ozempic tablets, Wegovy pill)1, 3, 4Weekly injection only: single-dose pen, single-dose or multi-dose vial, or multi-dose KwikPen2, 8
Oral optionYes. Wegovy pill for weight; Rybelsus and Ozempic tablets for type 2 diabetes1, 4, 5No. Every labeled form is an injection2, 8
Self-pay price (US)Injections: $349 a month for Wegovy (0.25 to 2.4 mg) and Ozempic (0.25 to 1 mg); Ozempic 2 mg $499 (per Nov 2025 announcement)9, 10. Wegovy pill: $149 to $299 a month by dose (at launch, Jan 2026)11Zepbound vial or KwikPen $299 to $449 a month by dose, with a refill within 45 days. Mounjaro $499 a month, all doses12, 13
Main side effectsNausea (44% vs 16% on placebo with Wegovy 2.4 mg), diarrhea, vomiting, constipation1Nausea (25% to 29% vs 8% on placebo with Zepbound), diarrhea, vomiting, constipation; hair loss 4% to 5% vs 1%2
Boxed warningThyroid C-cell tumors in rodents. Don't use with a personal or family history of medullary thyroid cancer or with MEN 21Same warning and same contraindication2

Evidence scale: 5 FDA-approved, 4 strong human, 3 limited human, 2 animal or lab only, 1 anecdotal. Prices are self-pay with a prescription, as checked November 1, 2026, and change often. Current per-dose Wegovy pill prices are Unverified.

Evidence by goal

Each goal is graded separately. Approved means an FDA-approved use. Trial data means human trial results but no approval for that use. "No study found" means no data in the sources we reviewed.

GoalSemaglutideTirzepatide
Weight lossApproved5/5Wegovy. STEP 1 (n=1,961): −14.9% vs −2.4% on placebo at 68 weeks14. The 25 mg pill: −13.6% vs −2.2% at 64 weeks15Approved5/5Zepbound. SURMOUNT-1 (n=2,539): −20.9% on 15 mg vs −3.1% on placebo at 72 weeks16
Type 2 diabetesApproved5/5Ozempic, Ozempic tablets and Rybelsus, for blood sugar3, 4, 5Approved5/5Mounjaro, for adults and children 10 and older8
Heart attack and stroke riskApproved5/5Wegovy, based on SELECT (n=17,604): 6.5% vs 8.0%, HR 0.80, in people with heart disease and overweight, without diabetes17, 1. Ozempic and Rybelsus have heart-risk indications in type 2 diabetes only3, 4Approved5/5Mounjaro, in type 2 diabetes at high heart risk (August 28, 2026)18. SURPASS-CVOT vs dulaglutide: HR 0.92, non-inferior; superiority not shown19. Not approved for heart risk without diabetes
Sleep apneaNo study foundNo data in the sources we reviewedApproved5/5Zepbound, the first drug approved for sleep apnea (with obesity). Breathing pauses −25.3 vs −5.3 per hour without CPAP20, 21
Kidney diseaseApproved5/5Ozempic, in type 2 diabetes. FLOW (n=3,533): 24% lower risk of kidney decline, kidney failure or death22, 3No study foundNo data: no kidney indication8
MASH (fatty liver)Approved5/5Wegovy, accelerated approval for noncirrhotic MASH with F2–F3 fibrosis. ESSENCE: resolved in 62.9% vs 34.3%23, 24No study foundNo data in the sources we reviewed. Not an approved use2, 8
Heart failure (HFpEF)Trial data4/5STEP-HFpEF (n=529): symptom score +16.6 vs +8.7. Not an approved use25Trial data4/5SUMMIT (n=731): heart death or worsening heart failure 9.9% vs 15.3%26. Not approved: Lilly withdrew the US application after FDA asked for another trial27

Head-to-head trials

  • SURMOUNT-5Tirzepatide vs semaglutidePublished
    Obesity without diabetes, n=751, 72 weeks, open label, highest tolerated dose (tirzepatide 10 or 15 mg; semaglutide 1.7 or 2.4 mg). Weight −20.2% vs −13.7%; waist −18.4 vs −13.0 cm. Stopped for stomach side effects 2.7% vs 5.6%28
  • SURPASS-2Tirzepatide vs semaglutide 1 mgPublished
    Type 2 diabetes, n=1,879, 40 weeks. A1C −2.01 to −2.30 points vs −1.86. Tirzepatide arms lost 1.9 to 5.5 kg more29, 30

Numbers from separate trials can't be ranked against each other: lengths (68 and 72 weeks), populations and analysis methods differ.

Side effects

All carry mostly stomach side effects that are worst while the dose is going up. Rates are each drug vs placebo in its own trials, not a head-to-head comparison.

EffectSemaglutideTirzepatide
SourceWegovy 2.4 mg vs placebo, label1Zepbound 15 mg vs placebo, label2
Nausea44% vs 16%28% vs 8%
Diarrhea30% vs 16%23% vs 8%
Vomiting24% vs 6%13% vs 2%
Constipation24% vs 11%11% vs 5%
Stopped for side effects6.8% vs 3.2% (Wegovy 2.4 mg, label)16.2% vs 2.6% (SURMOUNT-1, 15 mg)16
Stands outNAION, a sudden optic-nerve problem: a very rare side effect per Europe's regulator, up to 1 in 10,000. Not on US labels31, 1Hair loss 4% to 5% vs 1%2

Semaglutide and tirzepatide labels list warnings for serious allergic (hypersensitivity) reactions, pancreatitis, gallbladder disease, low blood sugar (with insulin or insulin secretagogues), kidney injury from dehydration, diabetic eye complications and inhaling stomach contents under anesthesia1, 2.

Key differences

  • Receptors. Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on both GIP and GLP-1 receptors1, 2.
  • Weight, head to head. In SURMOUNT-5, tirzepatide led to 20.2% weight loss vs 13.7% on semaglutide over 72 weeks28.
  • Approved uses. Semaglutide is also approved for kidney disease in type 2 diabetes, MASH, and heart risk in people without diabetes22, 23, 17. Tirzepatide is also approved for sleep apnea with obesity20.
  • Pill or injection. Semaglutide comes as a daily tablet as well as a weekly injection. Tirzepatide is injection only1, 2.
  • Side effects. Both cause mostly stomach side effects. In SURMOUNT-5, fewer people stopped tirzepatide for them (2.7% vs 5.6%)28.

Can you use both?

Don't combineLabel limit

The Zepbound label says using it with other tirzepatide products or any GLP-1 receptor agonist, which includes semaglutide, is not recommended2. Switching from one to the other is a prescriber's call.

FDA actions on GLP-1 compounding and retatrutide sellers are on the peptide regulatory tracker.

Where to get each

MoveWell sells nothing. Prices as checked November 1, 2026

DrugOptionFormPriceNotes
SemaglutideNovoCareWegovy or Ozempic pen$349 a month (Wegovy to 2.4 mg, Ozempic to 1 mg); Ozempic 2 mg $499 (per Nov 2025 announcement)9, 10Prescription needed. Also at retail pharmacies
SemaglutideNovoCareWegovy pill$149 (1.5 mg) to $299 (9 and 25 mg) a month at launch, Jan 202611Prescription needed. Current pill prices Unverified
SemaglutideNovoCare provider finderTelehealth prescriptionVaries by serviceNovoCare listed seven services in Jan 2026 and said it does not endorse them32
SemaglutideNovoCare coverage checkInsuranceDepends on planCoverage depends on your plan and diagnosis
TirzepatideLillyDirect ZepboundSingle-dose vial or multi-dose KwikPen$299 (2.5 mg), $399 (5 mg), $449 (7.5 to 15 mg) a month with a refill within 45 days; otherwise $499 to $69912Prescription needed. Vials need syringes bought separately. The single-dose pen is for insured patients
TirzepatideLillyDirect MounjaroSingle-dose pen$499 a month, all doses13Prescription needed. For type 2 diabetes

Left off: compounded copies and "research use only" vials. FDA declared the semaglutide shortage over on February 21, 202533; the tirzepatide shortage over in Oct 2024, confirmed December 19, 202434. The Fifth Circuit upheld both decisions on August 27, 202635, 36. Routine compounded copies are no longer allowed, and FDA says compounded drugs are not FDA-approved and not the same as generics37. More on the regulatory tracker. More options in the Semaglutide and Tirzepatide guides.

FAQ

Which causes more weight loss?

Tirzepatide. In SURMOUNT-5, people lost 20.2% on tirzepatide vs 13.7% on semaglutide over 72 weeks.

Which is better for type 2 diabetes?

Both are approved. In SURPASS-2, tirzepatide lowered A1C a little more than semaglutide 1 mg. Which fits depends on your other conditions.

Is there a tirzepatide pill?

No. If you want a pill, semaglutide comes as the Wegovy pill (weight) and as Rybelsus and Ozempic tablets (diabetes).

Which costs less?

Self-pay semaglutide injections are $349 a month for most doses (per Novo's Nov 2025 announcement); the Wegovy pill was $149 to $299 by dose at launch. Zepbound is $299 to $449 by dose if you refill within 45 days, and Mounjaro is $499.

Are compounded versions legal?

Routine compounded copies of both ended when their shortages ended, and a federal appeals court upheld both FDA decisions in Aug 2026.

References

37 sources, with links
  1. FDA. Wegovy (semaglutide) injection and tablets, prescribing information, revised 05/2026. PDF
  2. FDA. Zepbound (tirzepatide) prescribing information, revised 04/2026. PDF
  3. FDA. Ozempic (semaglutide) injection, prescribing information, revised 05/2026. PDF
  4. FDA. Rybelsus (semaglutide) tablets, prescribing information, revised 10/2025. PDF
  5. BNN Bloomberg. Novo to launch Ozempic pill for diabetes in second quarter of 2026 (Feb 4, 2026). Link
  6. BioSpace (FDA release). FDA approves novel, dual-targeted treatment for type 2 diabetes (May 13, 2022). Link
  7. BioSpace (FDA release). FDA approves new medication for chronic weight management (Nov 8, 2023). Link
  8. FDA. Mounjaro (tirzepatide) prescribing information, revised 08/2026. PDF
  9. ABC7. Cash price of popular weight-loss drug Wegovy dropping, manufacturer says (Nov 17, 2025). Link
  10. Fierce Pharma. Novo unveils newly reduced self-pay prices for Wegovy, Ozempic after White House deal (Nov 2025). Link
  11. KVIA (CNN Health). Starter dose of Wegovy now available as a daily pill instead of weekly injection (Jan 5, 2026). Link
  12. LillyDirect. Zepbound self-pay pricing (page dated Sep 2, 2026; checked Nov 1, 2026). Link
  13. LillyDirect. Mounjaro self-pay pricing (page dated Oct 14, 2026; checked Nov 1, 2026). Link
  14. Wilding JPH et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). NEJM 2021;384:989–1002. Abstract: J Endocr Soc 2021;5(Suppl 1):A10. PMC8089593
  15. AJMC. FDA approves oral semaglutide as first GLP-1 pill for weight loss (OASIS 4). Link
  16. Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). NEJM 2022;387:205–16. Ovid
  17. American College of Cardiology. SELECT trial summary (Lincoff, NEJM 2023;389:2221–32). Link
  18. Eli Lilly. FDA approves Lilly's Mounjaro (tirzepatide) to reduce cardiovascular risk (Aug 28, 2026). Link
  19. TCTMD. SURPASS-CVOT published: large trial confirms CVD efficacy of tirzepatide (Nicholls, NEJM 2025;393:2409–20). Link
  20. FDA. FDA approves first medication for obstructive sleep apnea (Dec 20, 2024). fda.gov
  21. American College of Cardiology. SURMOUNT-OSA trial summary (Malhotra, NEJM 2024;391:1193–205). Link
  22. HCPLive. FDA approves semaglutide (Ozempic) for type 2 diabetes and chronic kidney disease (Jan 28, 2025). Link
  23. HCPLive. FDA approves semaglutide (Wegovy) injection 2.4 mg for noncirrhotic MASH (Aug 15, 2025). Link
  24. Healio. Semaglutide tied to significant improvements in MASH, liver fibrosis at 72 weeks (ESSENCE; May 1, 2025). Link
  25. American College of Cardiology. STEP-HFpEF trial summary (Kosiborod, NEJM 2023;389:1069–84). Link
  26. American College of Cardiology. SUMMIT trial summary (Packer, NEJM 2024). Link
  27. ConscienHealth. Lilly withdraws tirzepatide application to FDA for heart failure (May 3, 2025). Link
  28. American College of Cardiology journal scan. SURMOUNT-5 (Aronne, NEJM 2025;393:26–36; Jul 10, 2025). Link
  29. AJMC. Complete data show tirzepatide brings greater A1C reduction, weight loss than semaglutide (SURPASS-2; Jun 25, 2021). Link
  30. GPnotebook. SURPASS-2: tirzepatide versus semaglutide once weekly in type 2 diabetes. Link
  31. European Medicines Agency. PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy (Jun 6, 2025). Link
  32. STAT. Telehealth swoops in offering Wegovy pill (Jan 6, 2026). Link
  33. Foley & Lardner. GLP-1 drugs: FDA removes semaglutide from drug shortage list (Feb 2025). Link
  34. Pharmacy Times. FDA affirms tirzepatide shortage resolved, sets transition period for compounding (Dec 2024). Link
  35. US Court of Appeals for the Fifth Circuit. Outsourcing Facilities Ass'n v. FDA, No. 25-10600 (tirzepatide), unpublished (Aug 27, 2026). PDF
  36. US Court of Appeals for the Fifth Circuit. No. 25-10758 (semaglutide shortage decision, affirming FDA), unpublished (Aug 27, 2026; revised Sep 1, 2026). PDF
  37. FDA. FDA warns 30 telehealth companies against illegal marketing of compounded GLP-1s (Mar 3, 2026). fda.gov

This page is for education and is not medical advice. Talk to a clinician before starting, stopping or switching any of these drugs.