Retatrutide: what it is, trial results, side effects and approval status

Retatrutide is a single synthetic peptide designed by Eli Lilly to activate three receptors at once: those for glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1) and glucagon. Lilly described it in 2022 under the code LY3437943, reporting that in cell assays it had balanced glucagon and GLP-1 activity with stronger GIP activity, and that its pharmacokinetics in people supported once-weekly dosing ^[1].

It is the next step in a line of incretin-based drugs: semaglutide acts on GLP-1 alone and tirzepatide on GIP and GLP-1. Retatrutide adds glucagon receptor activity. It is still an investigational drug. Lilly is testing it in phase 3 trials for obesity and its complications, type 2 diabetes and chronic kidney disease ^{[5] [9] [14]}.

Because of the trial headlines, retatrutide is widely sold online as a “research peptide”. Those products are not made or supplied by Lilly, and no licensed version exists. For what the research label does and does not mean, see what research peptides are.

Online, retatrutide is often shortened to “reta” or the reta peptide, and it is sometimes called “GLP-3”. There is no hormone called GLP-3. The nickname is a loose way of saying that retatrutide acts on a third receptor on top of the two targeted by tirzepatide. That third target is the glucagon receptor, which is why the scientific description is a triple GIP, GLP-1 and glucagon receptor agonist ^[1].

Searches for the retatrutide peptide therefore refer to the same investigational molecule, LY3437943. It is a single peptide chain, not a blend of three drugs.

GLP-1 and GIP receptor activity reduce appetite and food intake and improve insulin release, as with tirzepatide. The glucagon component is intended to add a different effect: glucagon raises energy expenditure and promotes fat use in the liver. In obese mice, Lilly’s researchers found that the glucagon-driven increase in energy expenditure added to the reduced calorie intake from GIP and GLP-1 activity, giving more weight loss than either alone ^[1].

The liver-fat results in people fit this idea. In a substudy of the phase 2 obesity trial, liver fat fell by 82.4% at 24 weeks on the 12 mg dose, and 86% of those participants reached normal liver fat levels, against none on placebo ^[4]. A separate Lilly study found that retatrutide delays gastric emptying, a known effect of GLP-1-based drugs ^[13].

The trial that brought retatrutide to wide attention was a 48-week phase 2 study in 338 adults with obesity, or overweight plus a weight-related condition, published in the New England Journal of Medicine in 2023. Participants received once-weekly retatrutide at 1 mg, 4 mg, 8 mg or 12 mg, or placebo ^[2].

At 24 weeks (the primary end point), average weight change was −7.2% on 1 mg, −12.9% on 4 mg, −17.3% on 8 mg and −17.5% on 12 mg, against −1.6% on placebo. At 48 weeks the figures were −8.7%, −17.1%, −22.8% and −24.2%, against −2.1% on placebo. On 12 mg, 83% of participants lost at least 15% of their body weight ^[2]. These are among the largest weight reductions reported for a drug in a randomised trial, though the trial was small and the phase 3 results are the more reliable guide.

A parallel phase 2 trial in 281 people with type 2 diabetes found dose-dependent reductions in HbA1c of up to about 2 percentage points at 24 weeks and weight loss of up to about 17% at 36 weeks on the higher doses ^[3].

The TRIUMPH programme consists of four phase 3 trials in more than 5,800 participants, covering weight management, obstructive sleep apnoea, knee osteoarthritis and people with cardiovascular disease ^[5]. As of September 2026, Lilly had announced topline results from all four by press release; we could not find any of them published in a peer-reviewed journal yet, so the figures below are the company’s own.

TRIUMPH-4 (announced December 2025) enrolled people with obesity and knee osteoarthritis. Lilly reported that participants on 12 mg lost an average of 28.7% of body weight at 68 weeks, alongside reductions in knee pain scores ^[6]. TRIUMPH-1 (announced May 2026) randomised 2,339 adults with obesity or overweight to 4 mg, 9 mg or 12 mg or placebo for 80 weeks. Using the efficacy estimand (which assumes people stay on treatment), weight fell by 19.0%, 25.9% and 28.3% on the three doses, against 2.2% on placebo ^[7].

TRIUMPH-2, in 1,152 adults with type 2 diabetes and obesity or overweight, and TRIUMPH-3, in 1,949 adults with a BMI of 35 or more and established cardiovascular disease, were announced in July 2026. Lilly reported weight loss of up to 20.8% in TRIUMPH-2 and up to 22.6% in TRIUMPH-3 on the efficacy estimand, against 4.0% and 3.2% on placebo ^[8].

The first phase 3 trial we found published in full is TRANSCEND-T2D-1, in The Lancet in June 2026. In 537 adults with type 2 diabetes managed by diet and exercise alone, retatrutide 4 mg, 9 mg and 12 mg lowered HbA1c by 1.69 to 1.94 percentage points over 40 weeks against 0.81 on placebo, and body weight by 11.5% to 15.3% against 2.6% ^[9].

The benefits studied in trials so far are weight reduction, blood-glucose control in type 2 diabetes, liver fat, knee pain in osteoarthritis and, in ongoing trials, sleep apnoea and kidney outcomes ^{[2] [3] [4] [5] [14]}. Only some of these have been reported in peer-reviewed journals, as set out above.

Retatrutide muscle loss is a common concern with any large weight reduction. A body-composition substudy of the phase 2 diabetes trial measured fat and lean mass by DXA scan. At 36 weeks, fat mass fell by 23.2% on 12 mg against 4.5% on placebo. The authors reported that the share of weight lost as lean mass was similar to that seen with other weight-loss treatments and with lifestyle interventions ^[16]. This was a small substudy, and it did not measure muscle strength or function.

In the phase 2 obesity trial, the share of people who lost at least 5%, 10% and 15% of body weight at 48 weeks was 92%, 75% and 60% on 4 mg; 100%, 91% and 75% on 8 mg; and 100%, 93% and 83% on 12 mg, against 27%, 9% and 2% on placebo ^[2].

In the phase 2 obesity trial, average weight change on 12 mg was −17.5% at 24 weeks and −24.2% at 48 weeks, so a large part of the effect was already present at six months and it continued to increase to the end of the trial ^[2]. The phase 3 TRIUMPH-1 results were measured at 80 weeks ^[7]. In type 2 diabetes, the TRANSCEND-T2D-1 HbA1c results were measured at 40 weeks ^[9].

The retatrutide half life measured in the phase 1b study was about 6 days, which is why the trials use once-weekly injections ^[15]. These are trial observations; there is no approved product whose label describes onset of effect.

Retatrutide vs tirzepatide is the most common comparison. The pharmacological difference is the glucagon receptor: tirzepatide acts on GIP and GLP-1 receptors, and retatrutide adds glucagon receptor activity ^[1]. Tirzepatide is a licensed medicine; retatrutide is not approved anywhere we could confirm. Our Retatrutide vs tirzepatide comparison sets the two side by side.

No head-to-head result has been published. In separate trials, retatrutide 12 mg produced −24.2% at 48 weeks in phase 2 ^[2], and tirzepatide 15 mg produced −20.9% at 72 weeks in SURMOUNT-1 ^[20]. Differences in populations, durations and trial design make that comparison unreliable. A phase 3 head-to-head trial, TRIUMPH-5, is randomising about 800 adults with obesity to retatrutide or tirzepatide, with the primary outcome at week 80; the registry record showed an estimated primary completion in November 2026 and no posted results ^[17].

Other next-generation drugs, such as the amylin analogue cagrilintide combined with semaglutide, are also in late-stage trials, but none has been compared with retatrutide. Switching from tirzepatide to retatrutide has no published protocol, because retatrutide is used only inside trials and the expanded access programme described below.

These two are sometimes compared online because both are discussed for abdominal fat, but they work in unrelated ways. Tesamorelin is an analogue of growth hormone-releasing factor. It is approved in the US, as Egrifta, only to reduce excess abdominal fat in adults with HIV who have lipodystrophy, and its label states that it is not indicated for weight loss management ^[21]. Retatrutide is an investigational incretin and glucagon receptor agonist studied for obesity ^[2]. They have never been compared in a trial.

Retatrutide has been given to several thousand people in randomised trials. The peer-reviewed human evidence as of September 2026 is the 2023 phase 2 trials ^{[2] [3]}, the liver-fat substudy ^[4] and the TRANSCEND-T2D-1 phase 3 trial ^[9]; the TRIUMPH results are so far available only as company announcements. None of this evidence applies to unlicensed retatrutide bought online, whose content has been shown to vary widely ^[10].

The phase 2 obesity trial used 1 mg, 4 mg, 8 mg and 12 mg by subcutaneous injection once weekly. The higher doses were reached by stepping up from a starting dose of 2 mg or 4 mg, and starting at 2 mg partly reduced gastrointestinal side effects ^[2]. The phase 2 diabetes trial tested 0.5 mg to 12 mg weekly ^[3]. The phase 3 trials use 4 mg, 9 mg and 12 mg once weekly ^{[7] [9]}.

In detail, the phase 2 obesity trial arms were 1 mg; 4 mg, started at 2 mg or 4 mg; 8 mg, started at 2 mg or 4 mg; and 12 mg, started at 2 mg and increased in steps ^[2]. The phase 1b study in type 2 diabetes tested multiple ascending weekly doses up to 12 mg ^[15]. Lilly reported that in TRIUMPH-1 the 4 mg dose was reached with a single escalation step ^[7]. These are the trial dose arms only; no retatrutide dosage chart exists outside trial protocols, and the doses were given under medical supervision.

These doses are reported from the trials for information only. They are not a recommendation, and there is no approved dose because there is no approved product. Online material labelled with a milligram amount may contain much less or much more than stated (see below), so trial doses cannot be reproduced from it. Our peptide calculator explains reconstitution arithmetic but cannot correct a wrong label.

Questions about how much bac water to add to a 10 mg or 30 mg vial, and how many units a given amount is, are arithmetic questions about concentration. They are answered here as arithmetic only. Nothing here is a dose or a protocol, and research material is not a medicine.

Concentration equals the amount of peptide divided by the volume of liquid. A vial labelled 10 mg mixed with 1 mL of bacteriostatic water would be 10 mg per mL; mixed with 2 mL it would be 5 mg per mL. A 30 mg vial mixed with 3 mL would also be 10 mg per mL. On a U-100 insulin syringe, 100 units equal 1 mL, so 10 units are 0.1 mL. At 10 mg per mL, 0.1 mL contains 1 mg; at 5 mg per mL it contains 0.5 mg. Our peptide calculator does this sum for any vial and volume, and the bacteriostatic water guide explains what the diluent is.

The arithmetic assumes the label is right. In the 2026 Australian study, three products labelled 10 mg contained 5.1 mg, 19.0 mg and 16.5 mg ^[10]. With those vials, the same volume would hold about half, or nearly twice, the amount the label implies. The FDA has also received reports of dosing errors with compounded GLP-1 drugs, including by clinicians calculating doses ^[18].

In trials, the most common side effects were gastrointestinal and dose-related: nausea, diarrhoea, vomiting and constipation. In the phase 2 obesity trial these were mostly mild to moderate, and heart rate rose in a dose-dependent way, peaking at 24 weeks and declining afterwards ^[2]. In TRIUMPH-1, Lilly reported nausea in 28.6%, 38.4% and 42.4% of participants on 4, 9 and 12 mg against 14.8% on placebo, and discontinuation because of adverse events in 4.1%, 6.9% and 11.3% against 4.9% ^[7]. In TRANSCEND-T2D-1, 2% to 5% stopped retatrutide because of adverse events, with no severe hypoglycaemia ^[9].

Products bought online carry extra, uncontrolled risks. A 2026 Australian study tested three products sold as retatrutide, each labelled 10 mg. All three contained the right peptide, but the measured content was 5.1 mg, 19.0 mg and 16.5 mg, meaning a user could receive about half or nearly double the intended amount ^[10]. A 2026 case report described a man with type 1 diabetes who developed severe vomiting, dehydration and high ketone levels after injecting online-purchased retatrutide; he also had a gut infection, so the authors could not establish cause ^[11].

Lilly’s TRIUMPH-1 announcement reported two side effects beyond the usual gastrointestinal ones. Dysaesthesia, an abnormal skin sensation such as tingling or burning, was reported by 5.1%, 12.3% and 12.5% on 4, 9 and 12 mg against 0.9% on placebo. Urinary tract infections were reported by 7.5%, 8.8% and 8.4% against 5.3% ^[7]. These are company figures that had not appeared in a peer-reviewed paper when we checked.

Retatrutide hair loss and tiredness are common searches. Neither was listed among the adverse events in the TRIUMPH-1 announcement we reviewed ^[7], and we did not find rates for them in the peer-reviewed phase 2 obesity trial summary ^[2]. That is not evidence that they do not occur; it means published figures are not yet available. For licensed GLP-1 drugs, hair loss and fatigue rates are given on the labels; see our tirzepatide guide.

On cancer, no published retatrutide trial has been long enough or large enough to assess cancer risk, and there is no approved label setting out warnings. The heart-rate rise seen in the phase 2 trial ^[2] is another reason the longer phase 3 safety data matter.

As of September 2026, retatrutide is not approved as a medicine by the FDA, the UK MHRA, the European Medicines Agency or, as far as we could find, any other regulator. Lilly has reported phase 3 results by press release ^{[6] [7] [8]}, but reported results are not an approval.

Retatrutide FDA approval status in 2026 is therefore simple: there is none. The FDA states that retatrutide is not a component of any FDA-approved drug, cannot be used in compounding under federal law, and has not been found safe and effective. It has warned telehealth companies marketing retatrutide and companies selling it labelled “for research purposes” ^[18]. See the US legal status page.

In the UK, the MHRA describes retatrutide as a medicine in clinical development that has not been approved for UK use, and says products outside clinical trials are likely to be illegal ^[19]; see the UK legal status page. The Australian TGA names retatrutide as an example of an unapproved peptide product ^[22]; our Australia legal status page covers that position, and the New Zealand page covers Medsafe’s.

Lilly has opened a pre-approval expanded access programme in the US, registered on ClinicalTrials.gov, under which a clinician can apply for individual patients who meet strict criteria ^[12]. This is not an approval and does not make retatrutide available on prescription. Retatrutide sold online is unlicensed; its legal position depends on the country, as summarised on our legal status pages.

Retatrutide clinical trials are listed on ClinicalTrials.gov, including the TRIUMPH and TRANSCEND programmes and the TRIUMPH-5 comparison with tirzepatide ^{[5] [14] [17]}. Taking part in a registered trial is the only route to retatrutide under medical supervision other than expanded access.

There is no licensed product with an approved storage label. Research material is normally sold as a freeze-dried powder; general practice for peptides of this kind is to keep it cold, dry and away from light, and to refrigerate it once reconstituted. See how to store peptides.

Does retatrutide need refrigeration? No manufacturer storage instructions for retatrutide are public, so any figure on a vendor website is the vendor’s own claim. For comparison only, the licensed tirzepatide pens are kept at 2 °C to 8 °C ^[20]. The FDA has received complaints about GLP-1 products bought outside the regulated supply arriving warm ^[18].

PepFinder does not sell retatrutide. If you are comparing research suppliers, see compare prices, read how to read a COA, and check third-party tested suppliers. Because published testing found content ranging from about half to nearly double the label, a certificate that states the measured quantity, not just purity, is essential.

UK listings on retatrutide UK prices are research-labelled products; the MHRA has said retatrutide outside clinical trials is likely to be illegal ^[19]. Our guides to third-party peptide testing and spotting a fake peptide supplier explain how to judge a test report.