Tirzepatide vs retatrutide: what the trials show

How they work

Tirzepatide is a once-weekly injection, and retatrutide was given as a once-weekly injection in clinical trials. Both activate hormone receptors. The difference is how many receptors each one activates.

Tirzepatide. The US Zepbound label says GLP-1 is a natural regulator of appetite and calorie intake, and nonclinical studies suggest GIP may add to the regulation of food intake. Both receptors are found in brain areas involved in appetite. The label says tirzepatide lowers calorie intake, likely by affecting appetite. The US Mounjaro label says it raises insulin release and lowers glucagon levels, both in a glucose-dependent manner.

Retatrutide. It adds the glucagon receptor to the two that tirzepatide activates, which is why it is called a triple agonist. The sources on this page do not describe what activating the glucagon receptor adds in people.

For the full picture of each, see the tirzepatide and retatrutide pages.

Development and approval status

Tirzepatide is an approved medicine with labels in the US and the EU. Retatrutide is still being tested and has no approval in the sources checked.

What comes next for retatrutide. On September 29, 2026, Eli Lilly said it "plans to submit a Biologics License Application (BLA) in Q1 2027 to the U.S. Food and Drug Administration." A submission is a request for review, not an approval. Lilly describes retatrutide as "an investigational molecule that cannot be legally sold or marketed for human use."

"Research purposes" products. As of October 1, 2026, the US FDA says it has warned companies that illegally sold unapproved drugs containing retatrutide falsely labelled "for research purposes" or "not for human consumption". It urges consumers not to buy these products, "which are of unknown quality and may be harmful to their health."

Weight loss trials side by side

Both medicines lowered weight more than placebo in their own trials. No trial recorded here gave people tirzepatide or retatrutide and compared them directly, so these are not head-to-head results.

Results are shown by dose group, from lowest to highest dose tested. They are trial groups, not treatment advice.

Reaching weight loss targets. In SURMOUNT-1, 85%, 89% and 91% of the three tirzepatide groups lost 5% or more of their weight, versus 35% with placebo. In the retatrutide phase 2 obesity trial, 100% of the highest dose group lost 5% or more, 93% lost 10% or more and 83% lost 15% or more at 48 weeks, versus 27%, 9% and 2% with placebo.

Longer follow-up for tirzepatide. In SURMOUNT-1 participants with obesity and prediabetes, mean weight change at 176 weeks (about 3 years) was -12.3%, -18.7% and -19.7% in the three tirzepatide groups, versus -1.3% with placebo. No retatrutide trial recorded here ran longer than 80 weeks.

After stopping tirzepatide. In SURMOUNT-4, people who switched from tirzepatide to placebo after 36 weeks gained 14.0% over the next 52 weeks, while those who continued lost a further 5.5%. No retatrutide trial on stopping treatment is recorded here.

The five published retatrutide trials recorded here were funded by Eli Lilly. The TRIUMPH-3 and TRIUMPH-4 figures come only from Lilly press releases and use the estimands Lilly reported.

Type 2 diabetes trials side by side

Both medicines have been studied in adults with type 2 diabetes. Again, the trials were separate, used different comparators and ran for different lengths of time.

Low blood sugar. No severe hypoglycaemia was reported in the retatrutide phase 2 diabetes trial or in TRANSCEND-T2D-1. The US Mounjaro label warns that people taking tirzepatide with insulin or a sulfonylurea may have a higher risk of hypoglycemia, including severe hypoglycemia.

Heart outcomes. SURPASS-CVOT is a completed heart outcome trial for tirzepatide. For retatrutide, Lilly reported heart event counts from TRIUMPH-3, a weight trial in people with cardiovascular disease: 44 MACE-5 events with retatrutide versus 52 with placebo (hazard ratio 0.82, 95% CI 0.55 to 1.22), and 27 MACE-3 events versus 23 (hazard ratio 1.12, 95% CI 0.64 to 1.96). Lilly said events were fewer than anticipated in all groups. These results are not peer reviewed.

Side effects as reported

Stomach and gut side effects were the most common with both medicines. Tirzepatide has a full US label. Retatrutide has no approved label, so its side effects come only from trial reports.

Retatrutide figures are listed by dose group, lowest to highest. "Not recorded here" means the fact files behind this page do not record that figure, not that the side effect does not occur.

Stopping retatrutide in other trials. In TRIUMPH-4, Lilly reported that 12.2% and 18.2% of the two retatrutide groups stopped because of side effects, versus 4.0% with placebo, and said this was highly correlated with starting BMI and included people who stopped for perceived excessive weight loss. In TRIUMPH-2, permanent stopping due to side effects or death was 12% and 8% in the middle and highest dose groups, versus 4% in the lowest dose group and 5% with placebo.

Tirzepatide label warnings. The US Zepbound label carries a boxed warning: tirzepatide caused thyroid C-cell tumors in rats, and it is unknown whether it causes them in humans. It must not be used by people with a personal or family history of medullary thyroid carcinoma or with Multiple Endocrine Neoplasia syndrome type 2. The label also lists acute pancreatitis, gallbladder disease, acute kidney injury from dehydration, serious allergic reactions and harm to an unborn baby. The Zepbound label says most nausea, vomiting and diarrhea "occurred during dose escalation and decreased over time."

Retatrutide outside trials. FDA Philippines says the public has no assurance of the quality, safety and efficacy of unregistered retatrutide products, and that using them may expose people to potential health risks, including possible injury or harm.

What is not yet known about retatrutide

Much less is known about retatrutide than about tirzepatide, because it has not finished the approval process. Based on the sources checked:

• Approval. No approval was found in the sources checked. Lilly plans to apply to the US FDA in the first quarter of 2027.
• Long-term safety. It has not been established. The longest published trials ran for 80 weeks. Tirzepatide has published follow-up to 176 weeks.
• A full label. There is no approved label, so there is no official list of warnings, people who should not use it, or interactions.
• Peer review of all phase 3 results. TRIUMPH-3 and TRIUMPH-4 results come only from Lilly press releases and had not been peer reviewed in the sources checked.
• Heart outcomes. The TRIUMPH-3 heart event counts are company-reported and not peer reviewed. No completed heart outcome trial like SURPASS-CVOT is recorded for retatrutide.
• Weight after stopping. No retatrutide trial on what happens after stopping is recorded here.
• A direct comparison. No head-to-head trial against tirzepatide was found.
• Other regulators. Its status with regulators in Europe, the UK, Japan, Australia and Canada was not checked on their own websites.

Legal status in the Philippines

Tirzepatide is listed as registered in the FDA Philippines Verification Portal as Mounjaro KwikPen and Mounjaro (checked October 7, 2026). The Philippine status of retatrutide is unverified: no record was found in an FDA Philippines Verification Portal search on October 7, 2026.

FDA Philippines advisories. FDA Philippines has warned the public against unregistered products containing each compound. Each advisory says the product has no Certificate of Product Registration.

A search of the FDA Philippines website for "retatrutide" on October 7, 2026 returned only the two retatrutide advisories and their Filipino versions (2026-1265-A and 2026-1392-A). Advisory No.2026-1392 asks local government units and law enforcement agencies to make sure the product is not sold in their areas.

Prescriptions. Under the Philippine Pharmacy Act (RA 10918, Sections 30 and 33), prescription medicines may be dispensed only by a registered and licensed pharmacist with a valid prescription from a physician, dentist or veterinarian, and only through a retail drug outlet licensed by FDA Philippines.

To check whether a product is registered, search the FDA Philippines verification portal at verification.fda.gov.ph. For more on Philippine rules, see are peptides legal in the Philippines.

How the two can and cannot be compared

The numbers on this page sit next to each other, but they do not answer which medicine works more. Here is what can and cannot be said from the sources.

What can be compared.

• Mechanism. Tirzepatide activates two receptors (GIP and GLP-1). Retatrutide activates the same two plus the glucagon receptor.
• Trial designs in broad terms. Both have phase 3, placebo-controlled weight trials in adults without diabetes (SURMOUNT-1 and TRIUMPH-1) and in adults with type 2 diabetes (SURMOUNT-2 and TRIUMPH-2).
• Most common side effects. For both, these were gastrointestinal.
• Status. Tirzepatide is approved in the US and the EU and listed as registered in the FDA Philippines Verification Portal (Mounjaro and Mounjaro KwikPen). Retatrutide is investigational.

What cannot be compared directly.

• No head-to-head trial. No trial recorded here randomized people to tirzepatide or retatrutide.
• Different lengths. SURMOUNT-1 and SURMOUNT-2 ran for 72 weeks. TRIUMPH-1 and TRIUMPH-2 ran for 80 weeks.
• Different people. Each trial had its own entry criteria. For example, SURMOUNT-1 also enrolled adults with overweight and a weight-related complication, while TRIUMPH-1 enrolled adults with obesity. Placebo groups also differed: -3.1% in SURMOUNT-1 and -3.9% in TRIUMPH-1.
• Different ways of reporting. Some retatrutide results were reported by Lilly using a treatment-regimen or efficacy estimand, and two phase 3 trials had not been peer reviewed in the sources checked.
• Different amounts of evidence. Tirzepatide has an approved label, a heart outcome trial and 176-week follow-up. Retatrutide does not.
• Side effect tables. The figures come from different trials and sources, so a higher number in one column does not show that one medicine causes more of a side effect than the other.

Trial averages do not predict how any one person will respond. Whether any medicine suits you is a decision for a licensed doctor. Label dose schedules for Mounjaro and Zepbound are on the tirzepatide page.