Retatrutide

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.

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].

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]}.

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.

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].

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. In July 2026 Lilly said it planned to submit retatrutide to the FDA in the first quarter of 2027 ^[8]. Any decision would come after that.

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.

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 and our bacteriostatic water guide.

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.