# Semaglutide vs Tirzepatide: FDA status and research

> Semaglutide vs tirzepatide: FDA approvals, receptor targets, half-life, compounding status, and the SURPASS-2 and SURMOUNT-5 head-to-head trials.

- Canonical URL: https://livingpluspeptides.com/compare/semaglutide-vs-tirzepatide/
- Last updated: October 25, 2026
- Publisher: Living+

| | Semaglutide | Tirzepatide |
| --- | --- | --- |
| FDA status | FDA approved. First U.S. approval 2017. Sold as Ozempic, Rybelsus and Wegovy [1, 2, 3] | FDA approved. First U.S. approval 2022. Sold as Mounjaro and Zepbound [4, 5] |
| Studied for | Labeled for type 2 diabetes, weight reduction, heart risk reduction and MASH liver disease [1, 2] | Labeled for type 2 diabetes, heart risk in type 2 diabetes, weight reduction and sleep apnea with obesity [4, 5] |
| Route | Under the skin once weekly, or tablets by mouth once daily [1, 2, 3] | Under the skin once weekly [4, 5] |
| Key trials | STEP 1 (weight), SELECT (heart events), SUSTAIN-6 [8, 16, 17] | SURMOUNT-1 (weight), SURPASS-2 and SURMOUNT-5 (both vs semaglutide) [9, 7, 6] |
| Receptors | GLP-1 receptor [1] | GIP and GLP-1 receptors [4] |
| Half-life | About 1 week (label) [1] | About 5 days (label) [4] |
| Shortage | FDA declared the shortage resolved on Feb 21, 2025 [10] | FDA declared the shortage resolved on Oct 2, 2024 and again on Dec 19, 2024 [10] |
| 503B bulks list | FDA proposed in 2026 not to include it. No final decision found as of Oct 25, 2026 [12, 13] | Same proposal and status as semaglutide [12, 13] |
| WADA | Not prohibited. Monitored in the 2026 Monitoring Program [14, 15] | Not prohibited. Monitored in the 2026 Monitoring Program [14, 15] |

Semaglutide and tirzepatide are both FDA-approved weekly shots for type 2 diabetes and weight. The main difference is the target. Semaglutide acts on one gut hormone receptor, GLP-1 [1]. Tirzepatide acts on two, GIP and GLP-1 [4]. In the SURMOUNT-5 head-to-head trial in adults with obesity, weight fell 20.2% with tirzepatide and 13.7% with semaglutide over 72 weeks [6].

## How they differ in design

Semaglutide is a copy of the gut hormone GLP-1 with a fatty side chain. The Ozempic label says it shares 94% of its sequence with human GLP-1 [1]. The label gives a half-life of about one week [1].

Tirzepatide is one peptide built on the GIP sequence. The Mounjaro label calls it a GIP receptor and GLP-1 receptor agonist [4]. It is a chain of 39 amino acids [18]. The label gives a half-life of about 5 days [4]. Both drugs are given once a week, and the long half-life is what allows this [1, 4].

## Approved uses and forms

Semaglutide comes as shots (Ozempic, Wegovy) and as daily tablets (Rybelsus, and Ozempic and Wegovy tablets) [1, 2, 3]. Wegovy is labeled for weight reduction, heart risk reduction in people with obesity or overweight, and a liver disease called MASH [2].

Tirzepatide comes only as a weekly shot [4, 5]. Mounjaro is labeled for type 2 diabetes and for lowering heart risk in adults with type 2 diabetes [4]. Zepbound is labeled for weight reduction and for obstructive sleep apnea in adults with obesity [5]. See the full [semaglutide](/peptides/semaglutide/) and [tirzepatide](/peptides/tirzepatide/) pages for label details.

## Head-to-head trials

Two trials compared the drugs directly. SURPASS-2 enrolled 1,879 adults with type 2 diabetes for 40 weeks. A1c fell 2.01 to 2.30 points with tirzepatide 5, 10 or 15 mg, and 1.86 points with semaglutide 1 mg [7].

SURMOUNT-5 enrolled 751 adults with obesity but without type 2 diabetes. It was an open-label phase 3b trial. People got the highest dose they could tolerate of tirzepatide (10 or 15 mg) or semaglutide (1.7 or 2.4 mg) once weekly for 72 weeks [6]. Weight fell 20.2% with tirzepatide and 13.7% with semaglutide. In both groups, the most common side effects were stomach related and mostly mild to moderate [6]. The trial was funded by the maker of tirzepatide [6].

Separate placebo trials found similar patterns. In STEP 1, semaglutide 2.4 mg lowered weight 14.9% vs 2.4% with placebo over 68 weeks [8]. In SURMOUNT-1, tirzepatide lowered weight 15.0% to 20.9% vs 3.1% with placebo over 72 weeks [9]. These trials had different people, so their numbers should not be compared directly [8, 9].

## Safety

Both labels carry a boxed warning for thyroid C-cell tumors seen in rodents. Neither should be used by people with a personal or family history of medullary thyroid cancer or MEN 2 [1, 4]. The most common side effects on both labels are stomach related, such as nausea, diarrhea, vomiting and constipation [1, 4].

## Compounding and the law

FDA has ended the shortages of both drugs. That closed the main legal path for mass compounding of copies [10]. FDA has received reports of adverse events tied to compounded versions of both drugs, and it warns that compounded products are not reviewed for safety or quality [11]. On April 30, 2026, FDA announced a proposal to keep both off the 503B bulks list. The Federal Register notice followed on May 1, 2026 [12, 13]. See the [FDA Peptide Status Tracker](/regulation/tracker/) for current status.

Neither drug is on the WADA 2026 Prohibited List. WADA tracks markers of both in its 2026 Monitoring Program [14, 15].

## Frequently asked questions

### Is tirzepatide stronger than semaglutide?

In SURMOUNT-5, weight fell 20.2% with tirzepatide and 13.7% with semaglutide over 72 weeks in adults with obesity without diabetes [6].

### What is the difference between semaglutide and tirzepatide?

Semaglutide acts on the GLP-1 receptor. Tirzepatide acts on both the GIP and GLP-1 receptors [1, 4].

### Are both semaglutide and tirzepatide FDA approved?

Yes. Semaglutide was first approved in 2017 and tirzepatide in 2022 [1, 4].

### Is there a tirzepatide pill?

No approved tirzepatide pill is on the current labels. Tirzepatide is labeled as a weekly shot [4, 5]. Semaglutide has approved tablets [3].

### Which lasts longer in the body?

Semaglutide has a half-life of about 1 week. Tirzepatide has a half-life of about 5 days [1, 4].

### Can semaglutide or tirzepatide still be compounded?

FDA ended both shortages. FDA does not plan to act on a pharmacy that fills four or fewer copies of either drug in a month [10].

## Sources

1. [DailyMed: Ozempic (semaglutide) injection label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79)
2. [DailyMed: Wegovy (semaglutide) injection and tablets label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b)
3. [DailyMed: Rybelsus and Ozempic (semaglutide) tablets label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98)
4. [DailyMed: Mounjaro (tirzepatide) injection label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0)
5. [DailyMed: Zepbound (tirzepatide) injection label](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b)
6. [Aronne et al. 2025, NEJM: SURMOUNT-5 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/40353578/)
7. [Frías et al. 2021, NEJM: SURPASS-2 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/34170647/)
8. [Wilding et al. 2021, NEJM: STEP 1 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/33567185/)
9. [Jastreboff et al. 2022, NEJM: SURMOUNT-1 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/35658024/)
10. [FDA: FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize](https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize)
11. [FDA: Concerns with unapproved GLP-1 drugs used for weight loss](https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)
12. [FDA: FDA proposes to exclude semaglutide, tirzepatide and liraglutide on 503B bulks list (Apr 30, 2026)](https://www.fda.gov/news-events/press-announcements/fda-proposes-exclude-semaglutide-tirzepatide-and-liraglutide-503b-bulks-list)
13. [Federal Register: List of bulk drug substances for which there is a clinical need under section 503B (May 1, 2026)](https://www.federalregister.gov/documents/2026/05/01/2026-08552/list-of-bulk-drug-substances-for-which-there-is-a-clinical-need-under-section-503b-of-the-federal)
14. [WADA: 2026 Monitoring Program](https://www.wada-ama.org/sites/default/files/2025-09/2026_list_monitoring_program_en_final_clean_september_2025.pdf)
15. [WADA: 2026 Prohibited List](https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf)
16. [Lincoff et al. 2023, NEJM: SELECT (PubMed)](https://pubmed.ncbi.nlm.nih.gov/37952131/)
17. [Marso et al. 2016, NEJM: SUSTAIN-6 (PubMed)](https://pubmed.ncbi.nlm.nih.gov/27633186/)
18. [Cardiovascular Diabetology 2022: Tirzepatide, a dual GIP/GLP-1 receptor co-agonist (PMC)](https://pmc.ncbi.nlm.nih.gov/articles/PMC9438179/)

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