# Retatrutide Explained: Trial Results, Side Effects and Approval Timeline > Retatrutide is an investigational once-weekly injection from Eli Lilly that activates GIP, GLP-1 and glucagon receptors. In the phase 3 TRIUMPH-1 trial, adults without diabetes lost an average of 28.3% of body weight at 80 weeks on the 12 mg dose (company-reported, not yet peer reviewed). As of September 2026 it is not approved anywhere; Lilly plans to file with the FDA in early 2027. - URL: https://glpcalendar.app/blog/retatrutide - Published: 2026-09-29 - Updated: 2026-09-29 - Publisher: GLP Calendar (https://glpcalendar.app) Retatrutide is an experimental obesity and diabetes medicine from Eli Lilly, the maker of Zepbound, and it is still in clinical trials. It has drawn attention for the large average weight loss seen in its studies, and because unapproved products sold online use its name. Here is what the published papers and Lilly's announcements show, as of September 2026. ## What is retatrutide and how does it work? Retatrutide (development code LY3437943) is an investigational once-weekly injection made by Eli Lilly. It is a single synthetic peptide that activates three hormone receptors: GIP, GLP-1 and glucagon. Semaglutide acts on GLP-1 only and tirzepatide on GIP and GLP-1, which is why retatrutide is called a triple agonist. GLP-1 and GIP signals reduce appetite and help control blood sugar. Glucagon, a hormone that acts mainly on the liver, is the new part, added for two reasons. ### Energy use In Lilly's discovery paper (Cell Metabolism, 2022), the glucagon component increased energy expenditure in obese mice, on top of the lower food intake driven by GIP and GLP-1. That is an animal result; how much it adds in people is still being studied. ### Liver fat A phase 2 substudy enrolled 98 people with fatty liver disease and at least 10% liver fat (Nature Medicine, 2024). At 24 weeks, liver fat fell by **81.4%** on 8 mg and **82.4%** on 12 mg, compared with a 0.3% rise on placebo. Normal liver fat (under 5%) was reached by 79% and 86% of those groups. Lilly is also testing retatrutide in this liver condition, called MASLD. ## What did the phase 2 trials show? In the 48-week phase 2 obesity trial published in NEJM in 2023, adults without diabetes lost an average of 24.2% of body weight on 12 mg, versus 2.1% on placebo. In a separate phase 2 trial in type 2 diabetes, the 12 mg group lost 16.9% of body weight at 36 weeks, and HbA1c fell by about 2 percentage points. ### Obesity trial (Jastreboff et al., NEJM 2023) The trial enrolled 338 adults with a BMI of 30 or more, or 27 to 30 plus a weight-related condition. Weekly doses of 1, 4, 8 or 12 mg were compared with placebo for 48 weeks. | Dose tested | Average weight change at 48 weeks | |---|---| | 1 mg | −8.7% | | 4 mg | −17.1% | | 8 mg | −22.8% | | 12 mg | −24.2% | | Placebo | −2.1% | At 12 mg, 83% of participants lost at least 15% of their body weight, compared with 2% on placebo. Side effects were mainly digestive, rose with dose and were mostly mild to moderate. They were partly reduced when the dose was built up more gradually. Heart rate rose with dose, peaked at 24 weeks and then declined. ### Type 2 diabetes trial (Rosenstock et al., Lancet 2023) This trial enrolled 281 adults with type 2 diabetes and an HbA1c of 7.0% to 10.5% at 42 US sites. Retatrutide was compared with placebo and with dulaglutide 1.5 mg (Trulicity). - **HbA1c at 24 weeks:** −2.02 percentage points on 12 mg, versus −0.01 on placebo and −1.41 on dulaglutide. - **Weight at 36 weeks:** −16.94% on 12 mg, versus −3.00% on placebo and −2.02% on dulaglutide. - **Stomach side effects:** reported by 35% of all retatrutide participants, 13% on placebo and 35% on dulaglutide. No severe low blood sugar occurred. ## What did the phase 3 TRIUMPH trials find? Four phase 3 TRIUMPH trials reported topline results between December 2025 and July 2026, and all showed large weight loss compared with placebo. The largest, TRIUMPH-1, reported an average loss of 28.3% at 80 weeks on 12 mg versus 2.2% on placebo. These are company-reported figures that have not yet been peer reviewed. | Trial (readout) | Who took part | Doses, length | Average weight change | |---|---|---|---| | TRIUMPH-4 (Dec 2025) | 445 adults with obesity or overweight and knee osteoarthritis | 9 or 12 mg, 68 weeks | −26.4% and −28.7% vs −2.1% | | TRIUMPH-1 (May 2026) | 2,339 adults with obesity or overweight, no diabetes | 4, 9 or 12 mg, 80 weeks | −19.0%, −25.9% and −28.3% vs −2.2% | | TRIUMPH-2 (Jul 2026) | 1,152 adults with obesity or overweight and type 2 diabetes | 4, 9 or 12 mg, 80 weeks | −12.7%, −19.1% and −20.8% vs −4.0% | | TRIUMPH-3 (Jul 2026) | 1,949 adults with severe obesity and cardiovascular disease | 9 or 12 mg, 80 weeks | −21.6% and −22.6% vs −3.2% | ### How to read these numbers Lilly headlines the efficacy estimand, which estimates results if everyone had stayed on treatment. The treatment-regimen estimand counts everyone randomized, including people who stopped. For TRIUMPH-1 that more conservative view gives −17.6%, −23.7% and −25.0% on 4, 9 and 12 mg, versus −3.9% on placebo. Both are averages; individual results vary widely. ### Other key results - **TRIUMPH-1:** 45.3% of people on 12 mg lost at least 30% of their weight. In a pre-specified extension, 532 people with a starting BMI of 35 or more continued to 104 weeks, with blinded increases to the highest tolerated dose; the group originally on 12 mg averaged **−30.3%**. - **TRIUMPH-4:** knee pain on the WOMAC scale fell by 4.5 points (75.8%) on 9 mg and 4.4 points (74.3%) on 12 mg, versus 2.4 points (40.3%) on placebo. - **TRIUMPH-2:** HbA1c fell by up to 1.6 percentage points at 80 weeks. - **TRIUMPH-3:** on 12 mg, triglycerides fell 37.0%, non-HDL cholesterol 16.5% and systolic blood pressure 9.3 mmHg. The comparison of major cardiovascular events was not conclusive (hazard ratio 0.82, 95% confidence interval 0.55 to 1.22). ### TRANSCEND-T2D-1: the first peer-reviewed phase 3 data Published in The Lancet in June 2026, this 40-week trial enrolled 537 adults with type 2 diabetes managed by diet and exercise alone. HbA1c fell by 1.69, 1.86 and 1.94 points on 4, 9 and 12 mg, versus 0.81 on placebo. Weight fell by 11.5%, 13.9% and 15.3%, versus 2.6%. Between 2% and 5% of retatrutide users stopped because of side effects, versus none on placebo, and no severe low blood sugar was reported. ## What are the side effects of retatrutide? In the trials, the most common side effects were digestive: nausea, diarrhea, constipation and vomiting, more often at higher doses. Two less familiar effects also appeared more often than with placebo: dysesthesia, an abnormal skin sensation, and urinary tract infections. The phase 2 obesity trial also showed a dose-related rise in heart rate. TRIUMPH-1, the largest trial, reported these rates: | Side effect | 4 mg | 9 mg | 12 mg | Placebo | |---|---|---|---|---| | Nausea | 28.6% | 38.4% | 42.4% | 14.8% | | Diarrhea | 25.2% | 34.1% | 32.0% | 13.5% | | Constipation | 23.8% | 25.9% | 26.1% | 10.9% | | Vomiting | 10.6% | 22.8% | 25.3% | 4.8% | | Dysesthesia | 5.1% | 12.3% | 12.5% | 0.9% | | Urinary tract infection | 7.5% | 8.8% | 8.4% | 5.3% | | Stopped due to side effects | 4.1% | 6.9% | 11.3% | 4.9% | ### Dysesthesia Dysesthesia means ordinary touch feels unusual or unpleasant, such as tingling, burning or skin sensitivity. The highest rate so far came from TRIUMPH-4: 8.8% on 9 mg and **20.9%** on 12 mg, versus 0.7% on placebo. TRIUMPH-2 reported 4.5% to 7.3% (placebo 0.7%) and TRIUMPH-3 reported 6.4% (placebo 1.3%). Lilly said most TRIUMPH-1 cases were mild to moderate and resolved during treatment. ### Stopping treatment In TRIUMPH-4, 12.2% on 9 mg and 18.2% on 12 mg stopped because of adverse events, versus 4.0% on placebo. Lilly said these stops were closely linked to starting BMI and included people who stopped because they felt they had lost too much weight. ### Heart rate In phase 2, heart rate rose with dose, peaked at 24 weeks and then declined. Lilly's phase 3 toplines did not report heart rate. For the timing of side effects with approved drugs, see [GLP-1 side effects week by week](https://glpcalendar.app/blog/glp-1-side-effects-timeline). ## When will retatrutide be approved? There is no approval date yet. As of September 2026, retatrutide is not approved by the FDA or any other regulator. On July 23, 2026, Lilly said it plans to submit a Biologics License Application to the FDA in the first quarter of 2027, for obesity, knee osteoarthritis pain and obstructive sleep apnea. An FDA decision can only follow that submission and a full review, and Lilly has not named a target date. Websites that give a specific approval month are guessing; treat those dates as unconfirmed. Outside the US it is the same: in August 2026 Lilly said no regulator anywhere had approved a retatrutide medicine, and that includes Canada, the EU and the UK. The only legal route is through Lilly's own studies: its clinical trials and, since June 2026, an expanded-access program listed on ClinicalTrials.gov that a doctor can ask about. ## Retatrutide vs tirzepatide: which causes more weight loss? Across separate trials, retatrutide has produced more average weight loss, but no head-to-head results exist yet. TRIUMPH-1 reported 25.0% to 28.3% at 80 weeks on 12 mg, depending on the analysis. Tirzepatide averaged 20.2% at 72 weeks in the SURMOUNT-5 trial. | Drug (brand) | Receptors activated | Key trial result | US status, Sept 2026 | |---|---|---|---| | Semaglutide (Wegovy) | GLP-1 | −13.7% at 72 weeks, 1.7 or 2.4 mg (SURMOUNT-5) | FDA-approved | | Tirzepatide (Zepbound) | GIP and GLP-1 | −20.2% at 72 weeks, 10 or 15 mg (SURMOUNT-5) | FDA-approved | | Retatrutide | GIP, GLP-1 and glucagon | −25.0% to −28.3% at 80 weeks, 12 mg (TRIUMPH-1) | Investigational; FDA filing planned Q1 2027 | Cross-trial comparisons are rough. SURMOUNT-5 was an open-label, head-to-head trial with no placebo group, in which people took the highest dose they tolerated. TRIUMPH-1 compared fixed doses with placebo, ran eight weeks longer, and enrolled a different population. TRIUMPH-5 will give the fair answer. It compares the two drugs over 80 weeks in about 800 adults with obesity, with percent weight change as the main outcome. ClinicalTrials.gov lists November 2026 as its estimated primary completion date. Side effects are also hard to compare across trials; both drugs mainly cause digestive effects. For more on each drug, see the [tirzepatide guide](https://glpcalendar.app/blog/tirzepatide) and the [semaglutide vs tirzepatide vs retatrutide comparison](https://glpcalendar.app/blog/semaglutide-vs-tirzepatide-vs-retatrutide). ## Is 'research grade' retatrutide safe to buy online? No. Anything sold online as retatrutide is an unapproved drug of unknown content and quality. FDA says retatrutide cannot be used in compounding under federal law. It has warned companies that sell it labeled 'for research purposes' or 'not for human consumption' while marketing it, often with dosing instructions, for people to inject. FDA's own summary, updated September 1, 2026, says retatrutide is not a component of any FDA-approved drug and has not been found safe and effective for any condition. The agency lists warnings sent to: - online sellers of 'research' products containing retatrutide and other GLP-1 drugs - telehealth companies marketing retatrutide, including directly to consumers - ingredient distributors selling retatrutide to compounders - outsourcing facilities that repackaged retatrutide FDA urges consumers not to buy these products, which it says are of unknown quality and may be harmful. Lilly went further in August 2026. It filed six lawsuits against US sellers, which it said included compounding pharmacies, medical spas and online 'research-use only' sellers. It also said it had referred more than 200 people and companies to regulators and law enforcement. The main risks are practical: - **Unknown identity and strength.** No regulator has checked what is in the vial or how much. - **Sterility.** An injection bypasses the body's outer defenses, so contamination can cause serious infection. - **Dosing mistakes.** There is no approved label, device or dose schedule, and trial doses were given under medical supervision. - **No screening.** Trials exclude people with certain conditions and monitor participants closely. A seller does neither. If you have already used a product sold as retatrutide, tell your clinician exactly what you took. Get urgent care for severe stomach pain that does not go away, repeated vomiting, signs of dehydration, or signs of an allergic reaction such as swelling or trouble breathing. You can report problems to FDA's MedWatch program. Our guide to [compounded GLP-1s and research peptides](https://glpcalendar.app/blog/compounded-glp-1-and-research-peptides) explains the wider rules. ## What to do next - **If you are curious about retatrutide,** ask your clinician whether a clinical trial could fit you. Trials are listed on ClinicalTrials.gov. - **If you want treatment now,** talk to your prescriber about FDA-approved options such as semaglutide or tirzepatide. - **Do not buy 'research' retatrutide.** The label does not make it legal or safe. - **Keep good records.** Whether you join a trial or start an approved medicine, a tracker such as GLP Calendar can log doses, side effects and weight so you can show your clinician exactly what happened. - **Watch for** Lilly's planned FDA submission in early 2027 and the TRIUMPH-5 results. We will update this page when they arrive. ## Frequently asked questions ### Can my doctor prescribe retatrutide now? No. As of September 2026 retatrutide is not approved, so it cannot be prescribed or filled at a pharmacy. It is available only through Lilly's own studies, including an expanded-access program registered on ClinicalTrials.gov in June 2026, and FDA says it cannot be used in compounding. ### Is retatrutide a peptide? Yes. It is a single synthetic peptide injected under the skin once a week. During development it carried the code name LY3437943. ### What is dysesthesia? Dysesthesia is an abnormal or unpleasant skin sensation, such as tingling, burning or sensitivity to touch. It was reported more often with retatrutide than with placebo in the phase 3 trials, and Lilly said most cases were mild to moderate. ### How is retatrutide different from Ozempic? Ozempic contains semaglutide, which activates only the GLP-1 receptor. Retatrutide also activates GIP and glucagon receptors. Ozempic is FDA-approved; retatrutide is still investigational. ### Is retatrutide approved in Canada, the UK or the EU? No. In August 2026 Lilly said that no medicine containing retatrutide had been approved for human use by any regulatory agency in the world. ## Sources - [Coskun et al. LY3437943 (retatrutide): from discovery to clinical proof of concept. Cell Metabolism, 2022](https://pubmed.ncbi.nlm.nih.gov/35985340/) - [Jastreboff et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med, 2023](https://pubmed.ncbi.nlm.nih.gov/37366315/) - [Rosenstock et al. Retatrutide for people with type 2 diabetes: a phase 2 trial. Lancet, 2023](https://pubmed.ncbi.nlm.nih.gov/37385280/) - [Sanyal et al. Retatrutide for metabolic dysfunction-associated steatotic liver disease: phase 2a substudy. Nature Medicine, 2024](https://pubmed.ncbi.nlm.nih.gov/38858523/) - [Eli Lilly. TRIUMPH-4 topline results in knee osteoarthritis, December 11, 2025](https://www.prnewswire.com/news-releases/lillys-triple-agonist-retatrutide-delivered-weight-loss-of-up-to-an-average-of-71-2-lbs-along-with-substantial-relief-from-osteoarthritis-pain-in-first-successful-phase-3-trial-302638804.html) - [Eli Lilly. TRIUMPH-1 topline results, 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 planned Q1 2027 FDA submission, 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) - [Bajaj et al. Retatrutide in type 2 diabetes treated with diet and exercise (TRANSCEND-T2D-1): phase 3 trial. Lancet, 2026](https://pubmed.ncbi.nlm.nih.gov/42250575/) - [Aronne et al. Tirzepatide as compared with semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med, 2025](https://pubmed.ncbi.nlm.nih.gov/40353578/) - [ClinicalTrials.gov. TRIUMPH-5: retatrutide compared with tirzepatide in adults with obesity (NCT06662383)](https://clinicaltrials.gov/study/NCT06662383) - [ClinicalTrials.gov. Retatrutide expanded-access program (NCT07629401), registered June 2026](https://clinicaltrials.gov/study/NCT07629401) - [FDA. FDA's 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) - [Eli Lilly. Lilly calls on platforms and regulators to shut down the illegal retatrutide black market, August 12, 2026](https://www.prnewswire.com/news-releases/lilly-calls-on-online-platforms-payment-companies-and-regulators-to-shut-down-the-illegal-retatrutide-black-market-302849551.html) --- Educational content, not medical advice. GLP Calendar is a tracking app; it does not recommend or calculate doses.