Retatrutide vs tirzepatide: what the trials show so far

Tirzepatide and retatrutide are both once-weekly injectable peptides from Eli Lilly, and retatrutide was designed as a step beyond tirzepatide. Tirzepatide activates the GIP and GLP-1 receptors and is a licensed medicine, sold as Mounjaro and, in the US, as Zepbound ^{[16] [17]}. Retatrutide activates those two receptors plus the glucagon receptor ^[1]. It is still investigational. The MHRA describes it as a medicine in clinical development that has not been approved for UK use ^[18], and the FDA states that it is not a component of any FDA-approved drug ^[20].

Retatrutide’s trials report larger average weight loss than tirzepatide’s. But the two have not yet been compared in a completed trial, the trials that exist differ in length and design, and most of retatrutide’s phase 3 results have so far appeared only as company announcements. Online shorthand such as reta vs tirzepatide usually refers to research-labelled products sold without a licence, which are not the drugs tested in these trials ^[21].

Searches such as GLP3 retatrutide and GLP-3 retatrutide use an informal nickname. There is no hormone called GLP-3. The name appears to refer to the three receptors retatrutide acts on, following GLP-1 drugs such as semaglutide and the dual agonist tirzepatide. Lilly’s researchers and the published trials describe retatrutide as a triple hormone receptor agonist, or a GIP, GLP-1 and glucagon receptor agonist ^{[1] [2]}.

In cell tests, retatrutide showed balanced glucagon and GLP-1 receptor activity but more GIP receptor activity ^[1]. The nickname can mislead: retatrutide does not work through a new hormone. It adds glucagon receptor activity to the two receptors tirzepatide already targets.

People comparing retatrutide vs Ozempic are comparing it with semaglutide, which acts on the GLP-1 receptor alone. Lilly is running a phase 3 trial of retatrutide against semaglutide in about 1,250 adults with type 2 diabetes, with an 80-week primary end point; results had not been published when we checked ^[23].

GIP and GLP-1 receptor activity reduce appetite and food intake and increase insulin release when blood glucose is raised. Both drugs share these effects ^{[16] [1]}. Retatrutide’s extra glucagon receptor activity is aimed at the other side of energy balance. In obese mice, Lilly’s researchers found that glucagon-driven increases in energy expenditure added to the reduced calorie intake from GIP and GLP-1 activity, giving more weight loss ^[1]. In a phase 1 single-dose study in people, retatrutide’s pharmacokinetics supported once-weekly dosing, the same schedule as tirzepatide ^{[1] [16]}.

Liver fat results in people fit the glucagon idea. In a substudy of the phase 2 obesity trial, 98 participants with fatty liver disease had their liver fat measured. At 24 weeks, liver fat fell by 81.4% on 8 mg and 82.4% on 12 mg, and 86% of those on 12 mg reached normal liver fat levels, against none on placebo ^[4]. Liver fat reductions tracked changes in body weight and in markers of insulin sensitivity ^[4].

Tirzepatide’s pivotal obesity trial, SURMOUNT-1, randomised 2,539 adults without diabetes to 5 mg, 10 mg or 15 mg weekly or placebo for 72 weeks. Average weight fell by 15.0%, 19.5% and 20.9% on the three doses, against 3.1% on placebo ^[13]. In SURMOUNT-5, a direct comparison with semaglutide, tirzepatide at the maximum tolerated dose produced 20.2% average weight loss at 72 weeks ^[14].

Retatrutide’s main peer-reviewed obesity trial is the 2023 phase 2 study in the New England Journal of Medicine. It enrolled 338 adults with obesity, or overweight plus a weight-related condition, and gave once-weekly retatrutide at 1 mg to 12 mg or placebo for 48 weeks. At 48 weeks, average weight loss was 8.7% on 1 mg, 17.1% on 4 mg, 22.8% on 8 mg and 24.2% on 12 mg, against 2.1% on placebo. On 12 mg, 83% of participants lost at least 15% of their body weight ^[2].

Those figures suggest retatrutide causes more weight loss, but the comparison is indirect. The retatrutide study was a phase 2 trial of 338 people over 48 weeks; SURMOUNT-1 was a phase 3 trial of 2,539 people over 72 weeks. A 2026 network meta-analysis in BMJ Medicine, which combined 58 randomised trials in adults without diabetes, estimated weight loss 22.10 percentage points greater than placebo for retatrutide and 19.28 points for tirzepatide. The authors cautioned that head-to-head evidence was limited and that confidence intervals overlapped for several comparisons ^[22].

Retatrutide’s phase 3 obesity results have so far come from Lilly. The TRIUMPH programme comprises four phase 3 trials in more than 5,800 participants ^[5]. In TRIUMPH-1, which randomised 2,339 adults with obesity or overweight to 4 mg, 9 mg or 12 mg or placebo for 80 weeks, average weight loss was reportedly 19.0%, 25.9% and 28.3% for people who stayed on treatment, against 2.2% on placebo. Counting everyone randomised, whether or not they stopped, the reported figures were 17.6%, 23.7% and 25.0%, against 3.9% ^[7]. Lilly also reported an average 28.7% weight loss at 68 weeks on 12 mg in TRIUMPH-4, in people with obesity and knee osteoarthritis ^[9]. We could not find these results in a peer-reviewed journal as of September 2026, so they are company figures.

Lilly is running a direct comparison. TRIUMPH-5, registered on ClinicalTrials.gov, is a phase 3, randomised, double-blind trial of retatrutide against tirzepatide in adults with obesity. It started in November 2024, aims to enrol about 800 people, and its primary end point is the percentage change in body weight at 80 weeks. The registry lists primary completion as estimated for November 2026, and the trial was active but no longer recruiting when we checked ^[10].

Until TRIUMPH-5 reports, any claim that retatrutide beats tirzepatide rests on comparing separate trials. The registry entry also shows who the answer will apply to. People who had taken weight-loss drugs in the 90 days before screening were excluded, so the trial will not show what happens when someone moves from one drug to the other ^[10].

In the UK, the retatrutide vs Mounjaro question has a regulatory answer before a clinical one. Mounjaro (tirzepatide) is a licensed prescription-only medicine for type 2 diabetes and for weight management ^[19]. Retatrutide is not. In October 2025 the MHRA described it as a medicine in clinical development that has not been approved for UK use, and said that products claiming to contain it outside authorised clinical trials are likely to be illegal. In the same operation the MHRA reported seizing more than 2,000 unlicensed retatrutide and tirzepatide pens awaiting dispatch ^[18].

The MHRA’s GLP-1 guidance adds that licensed GLP-1 medicines come as prefilled pens or tablets, and that powder in vials that must be mixed before injection is not authorised ^[19]. In the US, the FDA has warned about semaglutide, tirzepatide and retatrutide sold falsely labelled as being for research purposes ^[20]. Our UK legal status and US legal status pages summarise the wider rules, and the legal status overview covers other markets.

Both drugs lower blood glucose. In SURPASS-2, tirzepatide 5 mg to 15 mg lowered HbA1c by 2.01 to 2.30 percentage points over 40 weeks, more than semaglutide 1 mg ^[15]. Retatrutide’s first fully published phase 3 trial, TRANSCEND-T2D-1 in The Lancet, randomised 537 adults whose diabetes was managed by diet and exercise alone. Over 40 weeks, retatrutide 4 mg, 9 mg and 12 mg lowered HbA1c by 1.69 to 1.94 percentage points against 0.81 on placebo, and body weight by 11.5% to 15.3% against 2.6% ^[6].

The two trials are not directly comparable. SURPASS-2 started from a higher average HbA1c (8.28% against 7.9%) and compared tirzepatide with another active drug rather than placebo ^{[15] [6]}. Earlier, a phase 2 trial of 281 people with type 2 diabetes found HbA1c reductions of about 2 percentage points at 24 weeks on retatrutide 8 mg and 12 mg, and weight loss of about 17% at 36 weeks ^[3]. Lilly reported that in TRIUMPH-2, in adults with type 2 diabetes and obesity or overweight, weight fell by up to 20.8% at 80 weeks, with HbA1c reductions of up to 1.6 percentage points ^[8].

Both drugs cause the gastrointestinal effects typical of GLP-1-based medicines. Tirzepatide’s US label lists nausea, diarrhoea, vomiting and constipation among the most common adverse reactions; in the pooled Zepbound weight trials, nausea affected 25% to 29% of people on 5 mg to 15 mg against 8% on placebo ^[17]. In SURMOUNT-1, 4.3% to 7.1% stopped tirzepatide because of adverse events, against 2.6% on placebo ^[13]. The label carries a boxed warning about thyroid C-cell tumours in rats and also warns about pancreatitis, gallbladder disease and other risks ^[17].

Retatrutide has no approved label, so its side-effect profile comes only from trials. In the phase 2 obesity trial, gastrointestinal events were dose-related and mostly mild to moderate, and a lower starting dose partly reduced them. Heart rate rose in a dose-dependent way, peaked at 24 weeks and then declined ^[2]. In TRANSCEND-T2D-1, 2% to 5% stopped retatrutide because of adverse events, against none on placebo, and no severe hypoglycaemia was reported ^[6].

According to Lilly’s TRIUMPH-1 announcement, nausea was reportedly seen in 28.6%, 38.4% and 42.4% of people on 4, 9 and 12 mg, against 14.8% on placebo, and dysaesthesia (altered or unpleasant skin sensation) in 5.1% to 12.5%, against 0.9%. Stopping because of adverse events was reportedly 4.1%, 6.9% and 11.3%, against 4.9% on placebo ^[7]. The BMJ Medicine network meta-analysis found low-certainty evidence of higher discontinuation rates with retatrutide ^[22].

Rates from separate trials depend on dose steps, trial length and who took part, so they do not settle which drug is better tolerated. That is one of the questions TRIUMPH-5 was designed to answer ^[10].

The doses below are reported for information only; none is a recommendation. Tirzepatide has approved doses. The US Zepbound label starts at 2.5 mg once weekly, a dose used only to begin treatment, and gives maintenance doses of 5 mg, 10 mg or 15 mg for weight management, with 15 mg as the maximum ^[17]. Mounjaro has the same starting dose and the same maximum in adults ^[16].

Retatrutide has no approved dose, because there is no approved product. The phase 2 obesity trial tested 1 mg, 4 mg, 8 mg and 12 mg once weekly, with the higher doses reached from starting doses of 2 mg or 4 mg ^[2]. The phase 3 trials use 4 mg, 9 mg and 12 mg once weekly ^{[6] [7]}. Milligram figures for the two drugs describe different molecules and cannot be converted into each other.

Switching from tirzepatide to retatrutide has not been studied in any published trial, and there is no approved retatrutide product to switch to. Lilly states that retatrutide is legally available only to participants in its clinical trials ^[7]. The one other route is a US pre-approval expanded access programme on ClinicalTrials.gov. It is for single patients aged 18 or over with a BMI of at least 35 and two or more serious obesity-related complications, who have not responded to the best approved treatment and cannot join a trial ^[11].

The head-to-head trial will not fill this gap. TRIUMPH-5 excluded anyone who had taken weight-loss drugs in the 90 days before screening ^[10]. For licensed GLP-1 medicines, the MHRA advises consulting a healthcare professional before switching from one to another, because they differ in strength and use and switching without advice may increase side effects or reduce effectiveness ^[19].

Material sold online as retatrutide adds another unknown. A 2026 Australian analysis tested three products each labelled as 10 mg of retatrutide. All contained the peptide, but the measured amounts were 5.13 mg, 19.0 mg and 16.5 mg, from about half to almost double the stated content ^[21].

Tirzepatide is licensed in the UK and the US ^{[19] [16]}. Retatrutide is not approved in either country ^{[18] [20]}. Lilly has said it now has the clinical data to support submissions to regulators ^[8]; no regulator has published a decision.

PepFinder does not sell either peptide. Supplier listings we track for research-labelled material are on the retatrutide and tirzepatide price pages. Because published testing found retatrutide content ranging from about half to nearly double the label ^[21], our guides to third-party testing, reading a certificate of analysis and spotting a fake supplier explain what a certificate can and cannot show. How we assess suppliers is in our methodology, and nothing on this page is medical advice (see our disclaimer).