What's New: October 2026 Update

• TRIUMPH-1 published in full (September 29, 2026). The New England Journal of Medicine published the main Phase 3 obesity trial. The paper adds safety detail not in earlier announcements, including low blood pressure in 8.8% of participants on 12 mg against 0.9% on placebo.
• TRIUMPH-2 published in The Lancet (September 29, 2026) and presented at the EASD meeting: 20.8% average weight loss at 80 weeks on 12 mg in people with type 2 diabetes, if taken as intended.
• Submission plan unchanged. On September 29, Lilly repeated that it plans to submit retatrutide to the FDA in the first quarter of 2027.
• Court case pending. An appeals court heard arguments on September 24, 2026, over whether retatrutide is legally a biologic; no ruling had been published as of October 3.

What Is Retatrutide? The Short Version

Retatrutide (LY3437943) is an investigational once-weekly injection developed by Eli Lilly for obesity and related conditions. It is a peptide, a single molecule that activates three hormone receptors — GLP-1, GIP and glucagon — which is why it is often called a triple agonist, and sometimes nicknamed "GLP-3" online. The nickname refers to its three targets, not to a hormone of that name.

In Lilly's pivotal Phase 3 trial, TRIUMPH-1, participants on the highest dose lost an average of 28.3% of their body weight over 80 weeks (full TRIUMPH-1 results) if taken as intended, or 25.0% counting everyone who started. It is not approved by the FDA or any other regulator, and it is not available by prescription; see retatrutide's FDA approval status.

How Retatrutide Works

The drugs already approved for weight loss in this class act on one or two of the same receptors. Semaglutide acts on GLP-1. Tirzepatide acts on GLP-1 and GIP. Retatrutide adds a third.

The first two mainly reduce how much energy the body takes in. The glucagon receptor is the addition: according to Lilly, preclinical and early clinical data suggest retatrutide may also enhance energy expenditure and improve lipid metabolism. That receptor is what separates it from semaglutide and tirzepatide.

What the Phase 3 Trials Showed

Lilly has reported topline results from five Phase 3 trials: the first four trials of its TRIUMPH obesity program to report and the first trial of a separate type 2 diabetes program, TRANSCEND-T2D. Three have since been published in full: TRANSCEND-T2D-1 in The Lancet in June 2026, and TRIUMPH-1 in the New England Journal of Medicine and TRIUMPH-2 in The Lancet in September 2026.

All figures are for the 12 mg dose and assume participants took the drug as intended — the efficacy estimand. Counting everyone who was randomized, including those who stopped, TRIUMPH-1's figure was 25.0% and TRIUMPH-4's 23.7%.

The pattern across the table is consistent: weight loss was highest in the trials without diabetes, and lower in those that enrolled people with type 2 diabetes or established cardiovascular disease, though TRANSCEND-T2D-1 was also much shorter, at 40 weeks. About 500 TRIUMPH-1 participants continued to 104 weeks on 9 mg or 12 mg, depending on the highest dose they tolerated (Lilly described the group as 532 people with a BMI of 35 or more). Those originally assigned to 12 mg reached an average of 30.3%. How the weight loss built up over time is covered in the retatrutide weight loss timeline.

Beyond weight

• Obstructive sleep apnea. In a group within TRIUMPH-1 with moderate-to-severe sleep apnea, retatrutide reduced breathing interruptions by up to 36.1 events an hour, or 60.6%, from a starting average of 58.6, according to Lilly's June announcement, which assumed the drug was taken as intended; the published paper, using a different estimand, reports a reduction of up to 57.3%.
• Knee osteoarthritis pain. In TRIUMPH-1 participants with knee osteoarthritis, pain scores fell by up to 73.1% according to Lilly's June announcement (as intended), and by up to 61.6% in the published paper, which used a different estimand.
• Type 2 diabetes. In TRANSCEND-T2D-1, A1C fell by 1.9 percentage points at 12 mg and 2.0 at 9 mg, against 0.8 on placebo, over 40 weeks.
• Cardiovascular events. TRIUMPH-3, in people with established cardiovascular disease, recorded 27 major cardiovascular events among participants randomized to retatrutide and 23 among those randomized to placebo, with no statistically significant difference in either direction. It cannot show whether retatrutide raises or lowers cardiovascular risk.

How Retatrutide Compares With Existing Drugs

Head-to-head results against semaglutide or tirzepatide are not yet available. TRIUMPH-5, which compares retatrutide directly with tirzepatide in about 800 adults with obesity, has finished enrolling and is expected to finish around December 2026. Until it reports, any comparison is across separate trials (see retatrutide vs tirzepatide vs semaglutide). On comparable as-intended estimands, retatrutide 12 mg produced 28.3% over 80 weeks in TRIUMPH-1, tirzepatide 15 mg 22.5% over 72 weeks in SURMOUNT-1, and semaglutide 2.4 mg 16.9% over 68 weeks in STEP 1. The ordering is clear; the precise distances depend on populations and durations that were not the same. Semaglutide has also been approved since March 2026 at a higher 7.2 mg dose, which produces more weight loss than 2.4 mg.

The trade-off runs the other way on tolerability. In TRIUMPH-1, 11.2% of participants on 12 mg stopped because of side effects, against 6.2% on tirzepatide in SURMOUNT-1 and 7.0% on semaglutide in STEP 1.

Side Effects and Safety

As with the rest of this class, the most common side effects are gastrointestinal. In TRIUMPH-1 at 12 mg, 42.4% of participants reported nausea against 14.8% on placebo, 32.0% diarrhea against 13.5%, and 25.3% vomiting against 4.8%.

The side effect that has drawn most attention is dysesthesia — an altered sense of touch, such as tingling, burning, or ordinary contact feeling unpleasant. It was reported by 12.5% of participants on 12 mg in TRIUMPH-1, against 0.9% on placebo, and by 20.9% in TRIUMPH-4, against 0.7%. Lilly said the events were generally mild to moderate and that in TRIUMPH-1 most participants continued taking retatrutide; for TRIUMPH-4, it said they rarely led to discontinuation.

It is often described as retatrutide's own side effect. It is not. Semaglutide's US label, revised in June 2026, lists it at 2% against 1% on placebo in the three trials pooled for the 2.4 mg dose, and at 22% on 7.2 mg and 6% on 2.4 mg, against 0.3% on placebo, in the later trials that tested the higher dose; it says the incidence increases with dose. Tirzepatide's US label reports it in 0.4% of patients on 15 mg, against 0.1% on placebo. Retatrutide's rates were well above tirzepatide's and, at 12 mg in TRIUMPH-1, above semaglutide 2.4 mg's — comparisons across different trials, so approximate.

Tolerability varied by population. The share who stopped because of side effects at 12 mg ranged from 5.1% in TRANSCEND-T2D-1, a 40-week diabetes trial, to 18.2% in TRIUMPH-4, where participants also had knee osteoarthritis.

The full TRIUMPH-1 paper adds two findings not included in Lilly's May 2026 announcement: low blood pressure was reported in 8.8% of participants on 12 mg against 0.9% on placebo, more often in people also taking blood pressure medicines, and serious adverse events in 10.5% against 5.5%.

Is Retatrutide Approved?

No. Lilly plans to submit retatrutide to the FDA in the first quarter of 2027, and a standard review typically takes about a year from submission. Whether it will be filed as a biologic, as Lilly intends, is the subject of an unresolved legal dispute with the FDA.

Until then, in the US the only authorized routes to it are clinical trials and a narrow expanded-access program Lilly confirmed in August 2026 for patients who meet specific medical criteria and cannot enroll in a trial. Products sold online under the name are not sold or supplied by Lilly. Lilly warns that they "may contain unknown ingredients, harmful contaminants and impurities."

Retatrutide in Summary

Retatrutide acts on GLP-1, GIP and glucagon receptors in one molecule. In its pivotal Phase 3 trial it produced an average weight loss of 28.3% over 80 weeks if taken as intended, and participants originally on 12 mg who continued in an extension reached 30.3% at two years. More participants stopped because of side effects in that trial than in the pivotal trials of tirzepatide and semaglutide 2.4 mg, and its best-known side effect, dysesthesia, is shared with semaglutide, whose label lists it at 2% to 6% on 2.4 mg and 22% on 7.2 mg.

It is still an investigational medicine. What it will be approved for, on what label, and with what warnings will not be known until the FDA has reviewed it.

Sources

• Eli Lilly. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial. May 21, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, drove substantial improvements in weight, A1C, knee osteoarthritis pain, and obstructive sleep apnea. June 6, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. July 23, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes. March 19, 2026.
• Eli Lilly. Lilly's 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. December 11, 2025.
• Eli Lilly. What to know about retatrutide. Last updated September 2026.
• Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published September 29, 2026. DOI: 10.1056/NEJMoa2604169. (TRIUMPH-1)
• Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216.
• Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002.
• Novo Nordisk. Wegovy (semaglutide) US prescribing information, section 6.1. Revised June 2026.
• Eli Lilly. US prescribing information for tirzepatide for weight reduction, section 6.1. Revised August 2026.
• Eli Lilly Medical. What is the mechanism of action of retatrutide?
• Eli Lilly. A Study of Retatrutide (LY3437943) Compared to Tirzepatide (LY3298176) in Adults Who Have Obesity (TRIUMPH-5), NCT06662383. Lilly clinical trials listing.
• STAT. Eli Lilly to allow more patients to apply for special access to unapproved obesity drug. August 3, 2026.
• Eli Lilly. Lilly's triple agonist, retatrutide, delivered substantial weight loss and A1C reduction, underscoring its potential promise for people with obesity and type 2 diabetes. September 29, 2026.
• Reason. Can a new weight loss treatment escape the legal and regulatory thicket? September 10, 2026.

Medical Disclaimer: This article is for informational purposes only and is not medical advice. Retatrutide is investigational and is not approved by the FDA for any use. It is not available by prescription, and products sold online under its name are not sold or supplied by Lilly. Nothing here is a recommendation to use, seek out or avoid any medication. Results reported in clinical trials are averages across study populations and individual results vary. Treatment decisions belong with a qualified healthcare provider.