Semaglutide vs Tirzepatide: how the two molecules compare

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Semaglutide vs tirzepatide: how the two molecules work, their brands and approved uses, SURMOUNT-5 and SURPASS-2 results, side effects and dated prices. No winner declared.

By marketing Updated October 7, 2026 Facts checked October 6, 2026

Fact-checked against FDA labels and official sources; not yet reviewed by a licensed clinician. This page is education, not medical advice. Talk to your doctor before starting, stopping or changing any treatment.

Key takeaways

  • Semaglutide acts on the GLP-1 receptor; tirzepatide acts on both the GIP and GLP-1 receptors.[4]
  • In SURMOUNT-5, average weight change at 72 weeks was -20.2% with tirzepatide and -13.7% with semaglutide in adults with obesity without diabetes.[6]
  • Semaglutide has cardiovascular outcome evidence in people with obesity (SELECT), the basis of Wegovy's heart-risk indication.[8]
  • Tirzepatide (as Zepbound) is approved for obstructive sleep apnea in adults with obesity.[4]
  • Both mostly cause digestive side effects and share a boxed warning about thyroid C-cell tumors seen in rodents.[1]

The short answer

Semaglutide (Wegovy, Ozempic, Rybelsus) acts on the GLP-1 receptor; tirzepatide (Zepbound, Mounjaro) acts on both the GIP and GLP-1 receptors. Both are FDA approved for chronic weight management in their weight brands and mostly cause digestive side effects. In the head-to-head SURMOUNT-5 trial, average weight loss was larger with tirzepatide, while each molecule has outcome evidence and approved uses the other lacks.

Facts side by side

Semaglutide: one ingredient, several brandsFDA approved for weight managementPrescriptionInjectionTirzepatide: how the dual GIP/GLP-1 drug works (Zepbound, Mounjaro)FDA approved for weight managementPrescriptionInjection
PurposeChronic weight management (Wegovy); Glycemic control in type 2 diabetes (Ozempic)Chronic weight management (Zepbound); Moderate to severe obstructive sleep apnea (Zepbound); Glycemic control in type 2 diabetes (Mounjaro)
Class or typeGLP-1 receptor agonistGIP/GLP-1 dual agonist
Regulatory statusFDA approved for weight managementPrescriptionInjectionFDA approved for weight managementPrescriptionInjection
Prescription requiredYesYes
How it worksSemaglutide across its brands (Wegovy, Ozempic, Rybelsus): how it works, approved uses, STEP, SELECT and OASIS results, side effects and compounded versions.Tirzepatide (Zepbound, Mounjaro): how the dual GIP/GLP-1 agonist works, approved uses, SURMOUNT and SURPASS results, side effects and compounded versions.
How it is done or takenInjectionInjection
How oftenDaily, WeeklyWeekly
Average outcomes in studies
  • STEP 1: -14.9% vs -2.4% body weight (semaglutide 2.4 mg weekly vs placebo).
  • OASIS 4: -13.6% vs -2.2% body weight (oral semaglutide 25 mg daily vs placebo).
  • SURMOUNT-1: -15.0%, -19.5%, -20.9% (5, 10, 15 mg) vs -3.1% placebo.
  • SURMOUNT-4: Continued -5.5% vs +14.0% after switching to placebo.
Main risks
  • Thyroid C-cell tumors (boxed warning, rodents)
  • Acute pancreatitis
  • Acute gallbladder disease
  • Thyroid C-cell tumors (boxed warning, rats)
  • Acute pancreatitis
  • Acute gallbladder disease
Official resourcesdailymed.nlm.nih.govdailymed.nlm.nih.gov

What the trials showed

  • SURMOUNT-5 (NCT05822830) 751 adults with obesity, no type 2 diabetes, 72 weeks, open label, maximum tolerated doses: weight change -20.2% with tirzepatide vs -13.7% with semaglutide; waist -18.4 cm vs -13.0 cm.[6]
  • SURPASS-2 (NCT03987919) 1,879 adults with type 2 diabetes, 40 weeks, open label: tirzepatide 5/10/15 mg lowered HbA1c more than semaglutide 1 mg; extra weight differences 1.9, 3.6 and 5.5 kg.[7]

Side effects compared

Semaglutide: one ingredient, several brandsFDA approved for weight managementPrescriptionInjectionTirzepatide: how the dual GIP/GLP-1 drug works (Zepbound, Mounjaro)FDA approved for weight managementPrescriptionInjection
From the label
  • Nausea (44% vs 16% (Wegovy 2.4 mg); 15.8% to 20.3% vs 6.1% (Ozempic 0.5 to 1 mg))
  • Diarrhea (30% vs 16% (Wegovy); 8.5% to 8.8% vs 1.9% (Ozempic))
  • Vomiting (24% vs 6% (Wegovy); 5.0% to 9.2% vs 2.3% (Ozempic))
  • Constipation (24% vs 11% (Wegovy); 3.1% to 5.0% vs 1.5% (Ozempic))
  • Nausea (25% to 29% vs 8% (Zepbound); 12% to 18% vs 4% (Mounjaro))
  • Diarrhea (19% to 23% vs 8% (Zepbound); 12% to 17% vs 9% (Mounjaro))
  • Vomiting (8% to 13% vs 2% (Zepbound); 5% to 9% vs 2% (Mounjaro))
  • Constipation (11% to 17% vs 5% (Zepbound); 6% to 7% vs 1% (Mounjaro))

Things people weigh up

  • Approved uses: semaglutide brands carry cardiovascular, kidney (in type 2 diabetes) and MASH indications; tirzepatide brands carry obstructive sleep apnea and, for Mounjaro, cardiovascular risk reduction in type 2 diabetes.
  • Average weight loss in SURMOUNT-5 (open label, funded by the maker of tirzepatide) was larger with tirzepatide; individual responses vary widely.
  • Form: semaglutide is also available as a daily pill; tirzepatide is injection only.
  • Age: Wegovy injection is approved for teens 12 and older with obesity; Zepbound is for adults.
  • Side effects are mostly digestive with both; tolerability differs from person to person.
  • Price and coverage depend on brand, form, dose and plan, and change often.

These are the differences people commonly consider, not a recommendation. A clinician can help you decide what fits you.

In short: Semaglutide and tirzepatide are the two active ingredients behind today’s best-known weight-loss and diabetes medicines. Semaglutide acts on one gut-hormone receptor (GLP-1) and is sold as Wegovy, Ozempic and Rybelsus; tirzepatide acts on two (GIP and GLP-1) and is sold as Zepbound and Mounjaro. Both are FDA approved for chronic weight management in their weight brands. In SURMOUNT-5, the only head-to-head obesity trial so far, average weight loss was larger with tirzepatide, while each molecule has outcome evidence and approved uses the other does not (labels checked on 2026-10-06).

This page compares the molecules. If you are comparing the two weight-loss brands specifically, see Wegovy vs Zepbound. Neither molecule is “better” for everyone: the right fit depends on a person’s health, goals, side effects, coverage and preferences, and that is a conversation for you and your clinician.

How each one works

Semaglutide is a GLP-1 receptor agonist. It mimics GLP-1, a hormone released by the gut after eating, which helps the pancreas release insulin when blood sugar is high, slows stomach emptying and acts on appetite centers in the brain. Tirzepatide is a single molecule that activates both the GLP-1 receptor and the receptor for GIP, another gut hormone. According to the Zepbound label, nonclinical studies suggest the GIP action may further contribute to regulating food intake; exactly how much it adds in people is still being studied. Both are given as once-weekly injections; semaglutide is also available as daily tablets. Our GLP-1 guide explains the class in more detail.

Brands of each, and what they are approved for

BrandMoleculeFormApproved for (FDA label, checked 2026-10-06)
WegovySemaglutideWeekly injection; daily tabletChronic weight management (adults; teens 12+ for the injection); cardiovascular risk reduction in adults with heart disease and obesity or overweight; MASH with moderate to advanced fibrosis (injection, accelerated approval)
OzempicSemaglutideWeekly injection; daily tabletsType 2 diabetes, with heart and kidney outcome indications; not approved for weight management
RybelsusSemaglutideDaily tabletType 2 diabetes
ZepboundTirzepatideWeekly injection (pens, vials, KwikPen)Chronic weight management in adults; moderate to severe obstructive sleep apnea in adults with obesity
MounjaroTirzepatideWeekly injectionType 2 diabetes in adults and children 10+; cardiovascular risk reduction in adults with type 2 diabetes; not approved for weight management
Sources: DailyMed labels for each brand, checked on October 6, 2026.

Semaglutide has been on the market longer: Ozempic was first approved in December 2017 and Wegovy in June 2021. Tirzepatide followed with Mounjaro in May 2022 and Zepbound in November 2023.

What the trials showed

Weight, head to head (SURMOUNT-5). In this open-label trial, 751 adults with obesity and without type 2 diabetes took the highest tolerated weekly dose of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) for 72 weeks. Average weight change was -20.2% with tirzepatide and -13.7% with semaglutide, and waist size fell by 18.4 cm versus 13.0 cm. The trial was funded by Eli Lilly, the maker of tirzepatide, and participants knew which medicine they were taking. Averages hide a wide range: some people on either medicine lose much more or much less.

Blood sugar, head to head (SURPASS-2). In 1,879 adults with type 2 diabetes, tirzepatide at 5, 10 and 15 mg lowered HbA1c more than semaglutide 1 mg over 40 weeks, with extra weight differences of 1.9, 3.6 and 5.5 kg by dose. Semaglutide 1 mg is a diabetes dose, lower than the dose used for weight.

Heart, kidneys and liver. The two molecules have different outcome trials, which is why their labels differ. Semaglutide: SELECT showed fewer heart attacks, strokes and cardiovascular deaths in adults with heart disease and overweight or obesity without diabetes (6.5% vs 8.0% on placebo); FLOW showed a 24% lower risk of major kidney and cardiovascular events in adults with type 2 diabetes and chronic kidney disease; ESSENCE showed improvement in liver scarring in MASH. Tirzepatide: SURMOUNT-OSA showed fewer breathing interruptions in sleep apnea; SURPASS-CVOT, in adults with type 2 diabetes and heart disease, found major cardiovascular events in 12.2% on tirzepatide versus 13.1% on dulaglutide, another GLP-1 medicine, meeting the test for noninferiority but not superiority. No trial has compared the two molecules on heart or kidney outcomes.

Side effects compared

The side effects are similar in kind. In SURMOUNT-5, the most common adverse events with both were digestive, mostly mild to moderate and mainly during dose increases. On the labels, nausea was reported by 44% on Wegovy 2.4 mg versus 16% on placebo, and by 25% to 29% on Zepbound 5 to 15 mg versus 8% on placebo; these numbers come from different trials and cannot be compared directly. Both molecules share the class warnings: pancreatitis, gallbladder disease, low blood sugar with insulin or sulfonylureas, kidney injury from dehydration and aspiration during anesthesia, plus a boxed warning about thyroid C-cell tumors seen in rodents. The tirzepatide labels add advice for people on birth-control pills to use a non-oral or added barrier method for four weeks after starting and after each dose increase. Details: GLP-1 side effects.

Cost and coverage

Prices depend on the brand, form and dose, not on the molecule. Checked on October 6, 2026 on the manufacturers’ sites: Wegovy pens were $349 a month self-pay through NovoCare Pharmacy and Wegovy pills $149 to $299; Zepbound KwikPens were $299 to $449 a month self-pay through Lilly, by dose. Diabetes brands are usually covered differently from weight brands. Medicare’s temporary GLP-1 Bridge (July 2026 through 2027) covers Wegovy, Zepbound KwikPen and Foundayo for weight management with a $50 copay for people who meet its criteria. See Wegovy cost, Zepbound cost and the GLP-1 cost comparison tool.

After stopping

With both molecules, weight tends to come back after stopping. In STEP 4, people switched from semaglutide to placebo regained 6.9% of body weight over 48 weeks; in SURMOUNT-4, people switched from tirzepatide to placebo regained 14.0% over a year. Our guide to life after a GLP-1 covers what helps. Compounded versions of either molecule are not FDA approved; see compounded GLP-1s.

Compared with the items

FDA approved for weight managementPrescriptionInjectionSemaglutide: one ingredient, several brandsInjection · Daily, WeeklyFDA approved for weight managementPrescriptionInjectionTirzepatide: how the dual GIP/GLP-1 drug works (Zepbound, Mounjaro)Injection · Weekly

Related comparisons

GLP-1 Medication vs Bariatric SurgeryMethods

Related guides

GLP-1 Medications: how they work and which are approved for weightGLP-1 medications explained: what GLP-1 is, how the drugs work, which brands are FDA approved for…GLP-1 Side Effects: common, serious and how they are managedGLP-1 side effects from the FDA labels: common digestive effects by brand, serious risks, the thyroid…Stopping a GLP-1: regain, what trials show and keeping resultsWhat happens when you stop a GLP-1: STEP 1 extension, STEP 4, SURMOUNT-4 and BMJ meta-analysis…

Questions to ask a professional

  • Given my health conditions, do the approved uses of either molecule matter for me?
  • What results and side effects would be realistic for me with each?
  • Is a pill an option, and how does it compare with a weekly injection for me?
  • What does my insurance cover, and what would each cost per month?
  • How would we handle a switch, and what is the long-term plan?

Frequently asked questions

Is tirzepatide stronger than semaglutide?

In SURMOUNT-5, the head-to-head obesity trial, average weight loss was larger with tirzepatide (-20.2% vs -13.7% at 72 weeks). That trial was open label and funded by the maker of tirzepatide, and individual results vary. Semaglutide has outcome data and approvals that tirzepatide does not, and the reverse is also true.

Are semaglutide and tirzepatide the same drug class?

They overlap. Both act on the GLP-1 receptor; tirzepatide also acts on the GIP receptor, so it is called a dual GIP/GLP-1 receptor agonist.

Which brands contain semaglutide and which contain tirzepatide?

Semaglutide: Wegovy (weight and heart), Ozempic and Rybelsus (type 2 diabetes). Tirzepatide: Zepbound (weight and sleep apnea) and Mounjaro (type 2 diabetes).

Can you take semaglutide and tirzepatide together?

No. The labels say these products should not be used together with other GLP-1 receptor agonists. Any switch between them is planned by the prescriber.

References

  1. WEGOVY (semaglutide) injection and tablets: prescribing information. Novo Nordisk, via DailyMed, 2026. (accessed October 7, 2026) Drug label
  2. OZEMPIC (semaglutide) injection: prescribing information. Novo Nordisk, via DailyMed, 2026. (accessed October 7, 2026) Drug label
  3. RYBELSUS and OZEMPIC (semaglutide) tablets: prescribing information. Novo Nordisk, via DailyMed. (accessed October 6, 2026) Drug label
  4. ZEPBOUND (tirzepatide) injection: prescribing information. Eli Lilly and Company, via DailyMed, 2026. (accessed October 7, 2026) Drug label
  5. MOUNJARO (tirzepatide) injection: prescribing information. Eli Lilly and Company, via DailyMed, 2026. (accessed October 7, 2026) Drug label
  6. Aronne LJ, Horn DB, le Roux CW, et al.. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2416394 · PMID 40353578 · NCT05822830 (accessed October 6, 2026) Randomized trial
  7. Frias JP, Davies MJ, Rosenstock J, et al.. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2). New England Journal of Medicine, 2021. doi:10.1056/NEJMoa2107519 · PMID 34170647 · NCT03987919 (accessed October 7, 2026) Randomized trial
  8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al.. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). New England Journal of Medicine, 2023. doi:10.1056/NEJMoa2307563 · PMID 37952131 · NCT03574597 (accessed October 7, 2026) Randomized trial
  9. Perkovic V, Tuttle KR, Rossing P, et al.. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes (FLOW). New England Journal of Medicine, 2024. doi:10.1056/NEJMoa2403347 · PMID 38785209 · NCT03819153 (accessed October 7, 2026) Randomized trial
  10. Sanyal AJ, Newsome PN, Kliers I, et al.. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis (ESSENCE). New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2413258 · PMID 40305708 · NCT04822181 (accessed October 6, 2026) Randomized trial
  11. Malhotra A, Grunstein RR, Fietze I, et al.. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). New England Journal of Medicine, 2024. doi:10.1056/NEJMoa2404881 · PMID 38912654 · NCT05412004 (accessed October 6, 2026) Randomized trial
  12. Nicholls SJ, Pavo I, Bhatt DL, et al.. Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 Diabetes (SURPASS-CVOT). New England Journal of Medicine, 2025. doi:10.1056/NEJMoa2505928 · PMID 41406444 · NCT04255433 (accessed October 6, 2026) Randomized trial
  13. Rubino D, Abrahamsson N, Davies M, et al.. Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA, 2021. doi:10.1001/jama.2021.3224 · PMID 33755728 · NCT03548987 (accessed October 7, 2026) Randomized trial
  14. Aronne LJ, Sattar N, Horn DB, et al.. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA, 2024. doi:10.1001/jama.2023.24945 · PMID 38078870 · NCT04660643 (accessed October 7, 2026) Randomized trial
  15. Wegovy at NovoCare Pharmacy: self-pay prices. Novo Nordisk (NovoCare Pharmacy). (accessed October 7, 2026) Other
  16. Zepbound coverage and savings. Eli Lilly and Company. (accessed October 6, 2026) Other
  17. Medicare GLP-1 Bridge: information for providers. Centers for Medicare and Medicaid Services. (accessed October 7, 2026) Government page

Facts checked on October 6, 2026

Educational information, not medical advice. Talk with a qualified healthcare professional about your own situation. In an emergency call 911.