# Semaglutide vs Tirzepatide vs Retatrutide: Approval Status, Results and Side Effects

> Semaglutide (Ozempic, Wegovy, Rybelsus) and tirzepatide (Mounjaro, Zepbound) are approved in the US, Canada and the EU. Retatrutide is not approved by the FDA, Health Canada or the EU as of September 2026. It is still investigational, and Lilly plans to file with the FDA in early 2027. In trials, tirzepatide beat semaglutide head to head, and retatrutide showed the largest average losses.

- URL: https://glpcalendar.app/blog/semaglutide-vs-tirzepatide-vs-retatrutide
- Published: 2026-09-29
- Updated: 2026-09-29
- Publisher: GLP Calendar (https://glpcalendar.app)

Semaglutide, tirzepatide and retatrutide are once-weekly injectable peptides that act on gut-hormone receptors involved in appetite and blood sugar. Two of them are approved medicines with years of label data behind them. The third is still experimental. This guide compares their approval status in the US, Canada and the EU, how they work, what the trials showed and how their side effects differ, as of September 2026.

## Is retatrutide FDA approved?

No. As of September 2026, retatrutide is not approved by the FDA, by Health Canada or in the European Union. It is an investigational drug from Eli Lilly that has reported results from its main phase 3 obesity trials. Lilly says it plans to submit a Biologics License Application to the FDA in the first quarter of 2027.

Lilly reported topline results from TRIUMPH-1 in May 2026 and from TRIUMPH-2 and TRIUMPH-3 in July 2026. The company said it now has the clinical data to support global submissions for obesity, knee osteoarthritis pain and obstructive sleep apnea, but it has announced a timeline only for the US. Health Canada has not issued a Notice of Compliance for retatrutide, and the EU has no marketing authorization for it.

Until a regulator approves it, retatrutide has no official label, no approved dose and no approved product that a pharmacy can dispense.

## Which regulators have approved semaglutide, tirzepatide and retatrutide?

Semaglutide and tirzepatide are approved by the FDA, Health Canada and the European Commission. Retatrutide is approved by none of them. Brand names differ by region: the US and Canada sell tirzepatide as Mounjaro for type 2 diabetes and Zepbound for weight management, while the EU uses the Mounjaro name for both.

| Medicine and use | FDA (US) | Health Canada | EU (European Commission) |
|---|---|---|---|
| Semaglutide, type 2 diabetes | Yes: Ozempic (Dec 2017), Rybelsus pill (Sep 2019) | Yes: Ozempic (Jan 2018), Rybelsus (Mar 2020) | Yes: Ozempic (Feb 2018), Rybelsus (Apr 2020) |
| Semaglutide, weight management | Yes: Wegovy (Jun 2021), Wegovy pill (Dec 2025) | Yes: Wegovy injection (Nov 2021); pill not approved | Yes: Wegovy (Jan 2022), Wegovy pill (Jul 2026) |
| Tirzepatide, type 2 diabetes | Yes: Mounjaro (May 2022) | Yes: Mounjaro (Nov 2022) | Yes: Mounjaro (Sep 2022) |
| Tirzepatide, weight management | Yes: Zepbound (Nov 2023) | Yes: Zepbound (May 2025) | Yes: Mounjaro (Dec 2023) |
| Retatrutide, any use | No: investigational | No | No |

Dates are the first approval for each use. Later approvals added doses, devices and new uses, including heart, kidney, liver and sleep apnea indications in the US. The US Rybelsus label now also covers Ozempic tablets, a newer semaglutide tablet for type 2 diabetes.

### What "approved" means at each regulator

- **FDA (US):** the FDA approves a company's drug or biologics application after reviewing its evidence. The approved prescribing information sets the uses and doses, and the approval is recorded in the Drugs@FDA database.
- **Health Canada:** approval takes the form of a Notice of Compliance (NOC), issued to the manufacturer after a satisfactory review of its submission. Each approved product carries a Drug Identification Number (DIN).
- **EU:** the European Medicines Agency's scientific committee (CHMP) adopts an opinion, and the European Commission then grants a marketing authorization valid throughout the EU.

Approval in one region does not carry over to another. Each regulator runs its own review, which is why brand names, doses and dates differ. Canada, for example, approved tirzepatide for weight management as Zepbound KwikPen in May 2025, 18 months after the US.

## How do semaglutide, tirzepatide and retatrutide work?

All three imitate gut hormones, but they switch on different numbers of receptors. Semaglutide activates only the GLP-1 receptor. Tirzepatide activates the GIP and GLP-1 receptors. Retatrutide activates GIP, GLP-1 and glucagon receptors, which is why it is called a triple agonist.

| | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Receptors activated | GLP-1 | GIP and GLP-1 | GIP, GLP-1 and glucagon |
| Maker | Novo Nordisk | Eli Lilly | Eli Lilly |
| Approved forms | Weekly injection; daily pill | Weekly injection | None (trials only) |
| Half-life (US label) | About 1 week | About 5 days | No label yet |
| US label maintenance doses for weight | 1.7 or 2.4 mg weekly; up to 7.2 mg (Wegovy HD) | 5, 10 or 15 mg weekly | None; 4, 9 and 12 mg weekly were tested in phase 3 |

According to the Wegovy label, GLP-1 is a natural regulator of appetite and calorie intake, and its receptors sit in brain areas that control hunger. The Zepbound label adds that nonclinical studies suggest GIP "may further contribute" to regulating food intake. Retatrutide adds the glucagon receptor on top of both.

## Tirzepatide vs semaglutide: which leads to more weight loss?

Tirzepatide, on average. In SURMOUNT-5, the only published head-to-head trial of the two at weight-loss doses, adults with obesity and without diabetes lost an average of 20.2% of their body weight on tirzepatide and 13.7% on semaglutide after 72 weeks. Each person used the highest dose they tolerated.

The table collects the main trials. Figures are average changes in body weight, and each row is a separate trial.

| Trial | Drug and weekly dose | Length | Average weight change | Comparator |
|---|---|---|---|---|
| STEP 1 | Semaglutide 2.4 mg | 68 weeks | −14.9% | −2.4% placebo |
| SURMOUNT-1 | Tirzepatide 5 / 10 / 15 mg | 72 weeks | −15.0% / −19.5% / −20.9% | −3.1% placebo |
| SURMOUNT-5 | Tirzepatide 10–15 mg vs semaglutide 1.7–2.4 mg | 72 weeks | −20.2% vs −13.7% | Head to head |
| Retatrutide phase 2 (NEJM 2023) | Retatrutide 1 / 4 / 8 / 12 mg | 48 weeks | −8.7% / −17.1% / −22.8% / −24.2% | −2.1% placebo |
| TRIUMPH-1 (topline) | Retatrutide 4 / 9 / 12 mg | 80 weeks | −17.6% / −23.7% / −25.0% | −3.9% placebo |

### How much weight did people lose on retatrutide?

In TRIUMPH-1, which enrolled 2,339 adults with obesity or overweight and without diabetes, the 12 mg dose produced an average loss of 25.0% at 80 weeks when everyone randomized was counted. Lilly puts the figure at 28.3% if everyone had stayed on treatment. Two more phase 3 trials reported in July 2026:

- **TRIUMPH-2** (obesity or overweight with type 2 diabetes, 80 weeks): −12.7%, −19.1% and −20.8% on 4, 9 and 12 mg, versus −4.0% with placebo. A1C fell by up to 1.6 percentage points.
- **TRIUMPH-3** (severe obesity with established heart disease, 80 weeks): −21.6% on 9 mg and −22.6% on 12 mg, versus −3.2% with placebo.

These are company-reported toplines that have not yet been peer reviewed. The TRIUMPH-2 and TRIUMPH-3 figures assume everyone stayed on treatment, which gives higher numbers than the whole-group TRIUMPH-1 figures in the table.

### Why these numbers are not a head-to-head ranking

Only SURMOUNT-5 compared two of these drugs directly. The other trials enrolled different people, lasted 48 to 80 weeks and used different statistical methods, so side-by-side percentages are a rough guide rather than a ranking. No head-to-head results comparing retatrutide with tirzepatide had been published as of September 2026. All of these figures are averages: individual results vary, and people with type 2 diabetes lost less weight in these trials, as TRIUMPH-2 shows.

## How do the side effects compare?

All three drugs mainly cause stomach and bowel side effects: nausea, diarrhea, vomiting and constipation. Rates rise with dose. The Wegovy and Zepbound labels say these effects were most often reported during dose escalation, and the Zepbound label adds that they decreased over time. Retatrutide's trials also recorded changes in skin sensation (dysesthesia) more often than with standard doses of the other two.

| Side effect | Semaglutide 2.4 mg (Wegovy label) | Tirzepatide 15 mg (Zepbound label) | Retatrutide 12 mg (TRIUMPH-1 topline) |
|---|---|---|---|
| Nausea | 44% vs 16% | 28% vs 8% | 42.4% vs 14.8% |
| Vomiting | 24% vs 6% | 13% vs 2% | 25.3% vs 4.8% |
| Diarrhea | 30% vs 16% | 23% vs 8% | 32.0% vs 13.5% |
| Constipation | 24% vs 11% | 11% vs 5% | 26.1% vs 10.9% |
| Stopped due to side effects | 6.8% vs 3.2% | 6.7% vs 3.4% | 11.3% vs 4.9% |

The second number in each cell is placebo. The trials differ, so compare with care.

Dysesthesia means tingling, burning or unusually sensitive skin. The Wegovy label reports it in 22% of people on the 7.2 mg dose, compared with 6% on 2.4 mg and 0.3% on placebo. In TRIUMPH-1 it affected 12.5% of people on retatrutide 12 mg versus 0.9% on placebo; Lilly says most cases were mild to moderate.

The semaglutide and tirzepatide labels share the same class warnings. These include a boxed warning about thyroid C-cell tumors seen in rodents (the drugs are not for people with a personal or family history of medullary thyroid cancer or MEN 2), pancreatitis, gallbladder problems, low blood sugar when combined with insulin or a sulfonylurea, kidney problems from dehydration, and serious allergic reactions. Retatrutide has no label yet, so its full safety profile is still under review.

The Zepbound Medication Guide tells patients to stop the medicine and call their healthcare provider right away for severe stomach pain that will not go away, with or without vomiting. It says to get medical help right away for signs of a serious allergic reaction, such as swelling of the face, lips, tongue or throat, or problems breathing or swallowing. It also says to tell your provider right away about nausea, vomiting or diarrhea that does not go away, because fluid loss can lead to kidney problems.

## Why does it matter that retatrutide is not approved?

Because nothing sold as "retatrutide" outside a clinical trial has been checked by a regulator. The FDA says retatrutide has not been found safe and effective for any condition, cannot legally be used in compounding, and should not be bought from sellers that label it as being for research purposes or not for human consumption.

The FDA's page on unapproved GLP-1 drugs, updated September 1, 2026, says the agency has warned companies that illegally sold unapproved drugs containing semaglutide, tirzepatide, retatrutide, survodutide or mazdutide. These products were falsely labeled "for research purposes" or "not for human consumption" and sold directly to consumers with dosing instructions. The FDA urges consumers not to buy them because they are of unknown quality and may be harmful. It has also warned telehealth companies that marketed retatrutide, ingredient distributors that sold it to compounders, and outsourcing facilities that repackaged it.

The risks are practical:

- **Unknown contents.** With no approved product to compare against, a buyer cannot know a vial's real dose, purity or sterility.
- **No medical oversight.** Trial participants are screened and followed closely, with side effects recorded. A gray-market buyer has none of that.
- **No label.** There are no approved doses, interaction warnings or Medication Guide to rely on.

This guide gives no dosing information for retatrutide beyond the doses tested in trials. If you are interested in the drug, ask your clinician whether a clinical trial might suit you; trials are listed on ClinicalTrials.gov. Our guide to [compounded GLP-1s and research peptides](https://glpcalendar.app/blog/compounded-glp-1-and-research-peptides) explains the legal differences in more detail.

## When could retatrutide be approved?

Not in the US before 2027. Lilly plans to submit its application to the FDA in the first quarter of 2027, and approval can only follow the FDA's review. As of September 2026, Lilly has not announced submission dates for Health Canada or the European Medicines Agency.

Any approval date quoted online before an application is filed is a forecast, not a fact. Our [retatrutide guide](https://glpcalendar.app/blog/retatrutide) tracks each trial readout and filing, and the [full list of GLP-1 medications](https://glpcalendar.app/blog/glp-1-medications-list) shows where it sits among the other drugs in development.

## Bottom line

- **Semaglutide and tirzepatide** are approved in the US, Canada and the EU. Tirzepatide produced more weight loss on average in the one head-to-head trial, but the right choice also depends on your other conditions, the form you prefer (weekly shot or daily pill), side effects and cost. Our [semaglutide](https://glpcalendar.app/blog/semaglutide) and [tirzepatide](https://glpcalendar.app/blog/tirzepatide) guides cover each label in detail.
- **Retatrutide** is not approved anywhere as of September 2026. The only legitimate way to receive it today is through Lilly's own studies: its clinical trials or its expanded-access program.
- **Switching drugs is a prescriber decision.** Bring your questions, and your records, to that conversation.

If you do switch between medicines, a tracker such as GLP Calendar can log each product, dose and injection date so your prescriber sees the full history at your next visit.

## Frequently asked questions

### Is retatrutide approved in Canada or Europe?

No. As of September 2026, Health Canada has not issued a Notice of Compliance for retatrutide, and there is no EU marketing authorization. Lilly has announced a US filing plan for early 2027 but has not given dates for other regions.

### Is retatrutide stronger than tirzepatide?

In separate trials, retatrutide produced larger average weight loss than tirzepatide, but those trials enrolled different people and ran for different lengths of time. No head-to-head results comparing the two had been published as of September 2026.

### Are Mounjaro and Zepbound the same medicine?

Yes. Both contain tirzepatide made by Eli Lilly. In the US and Canada, Mounjaro is the diabetes brand and Zepbound is the weight-management brand, while the EU uses the Mounjaro name for both uses.

### What does triple agonist mean?

It means one molecule activates three hormone receptors. Retatrutide activates the GIP, GLP-1 and glucagon receptors, tirzepatide activates two (GIP and GLP-1), and semaglutide activates one (GLP-1).

### Is it legal to buy retatrutide sold as a research peptide?

The FDA says products containing retatrutide that are labeled for research purposes or not for human consumption, but sold to consumers, are illegally marketed unapproved drugs. It urges people not to buy them because their quality is unknown and they may be harmful.

## Sources

- [Drugs@FDA: approval histories for Ozempic, Rybelsus, Wegovy, Mounjaro and Zepbound (US FDA, accessed September 2026)](https://www.accessdata.fda.gov/scripts/cder/daf/)
- [Health Canada Notice of Compliance database: Ozempic, Rybelsus, Wegovy, Mounjaro and Zepbound (accessed September 2026)](https://health-products.canada.ca/noc-ac/?lang=eng)
- [European Medicines Agency, medicine data: EU authorization dates for Ozempic and Rybelsus (accessed September 2026)](https://www.ema.europa.eu/en/medicines/download-medicine-data)
- [European Medicines Agency: Wegovy EPAR, including the 2026 tablet extension](https://www.ema.europa.eu/en/medicines/human/EPAR/wegovy)
- [European Medicines Agency: Mounjaro EPAR, including the 2023 weight-management extension](https://www.ema.europa.eu/en/medicines/human/EPAR/mounjaro)
- [Wegovy (semaglutide) US prescribing information, June 2026, with STEP 1 results as Study 2 (DailyMed)](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b)
- [Zepbound (tirzepatide) US prescribing information and Medication Guide, August 2026, with SURMOUNT-1 results as Study 1 (DailyMed)](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b)
- [Aronne et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). NEJM, 2025](https://www.nejm.org/doi/abs/10.1056/NEJMoa2416394)
- [Jastreboff et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. NEJM, 2023](https://pubmed.ncbi.nlm.nih.gov/37366315/)
- [Eli Lilly: TRIUMPH-1 phase 3 topline results for retatrutide, May 21, 2026](https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss-in-pivotal-phase-3-obesity-trial-302778859.html)
- [Eli Lilly: TRIUMPH-2 and TRIUMPH-3 topline results and FDA submission plan, July 23, 2026](https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-successful-in-two-additional-phase-3-obesity-trials-delivering-significant-improvements-in-weight-and-a1c-302832674.html)
- [US FDA: Concerns with unapproved GLP-1 drugs used for weight loss (updated September 1, 2026)](https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss)

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Educational content, not medical advice. GLP Calendar is a tracking app; it does not recommend or calculate doses.