What is retatrutide?
Retatrutide is a once-weekly injection that mimics three hormones involved in appetite, blood sugar, and how the body uses energy:
- GLP-1: lowers appetite and blood sugar
- GIP: lowers appetite and blood sugar
- Glucagon: increases energy expenditure and the breakdown of stored fat, including fat in the liver
The glucagon component is what separates retatrutide from semaglutide, which mimics one hormone (GLP-1), and tirzepatide, which mimics two (GLP-1 and GIP).
Activating the glucagon receptor appears to raise the body’s energy use and shift it toward burning stored fat, an effect the GLP-1/GIP combination doesn’t reproduce. This is also why retatrutide is being studied for metabolic dysfunction-associated steatotic liver disease (MASLD), where reducing liver fat is a primary clinical goal.
That mechanism is the leading explanation for the larger weight-loss numbers retatrutide has produced in trials.
Eli Lilly is targeting an FDA submission for retatrutide in late 2026, after the largest of its Phase 3 trials are published.2
What is the average weight loss on retatrutide?
The clearest answer to date comes from a Phase 2 trial published in the New England Journal of Medicine in 2023, which reported 24.2% weight loss after 48 weeks at the highest dose in 338 adults with obesity but no other complications.3
The most recent published data is from TRIUMPH-4, a Phase 3 trial of 445 adults with obesity and knee osteoarthritis. Over 68 weeks, the 12 mg dose led to a 28.7% body-weight loss, the 9 mg dose to 26.4%, and the placebo to 2.1%.1
The 28.7% figure makes the headlines, but it comes from a specific subpopulation.
The general obesity figure from TRIUMPH-1 (the largest trial in the programme) hasn’t been published yet.
Most clinicians expect it to be somewhere between the Phase 2 and TRIUMPH-4 numbers when full results arrive in summer 2026.
TRIUMPH-4 also reported clinically meaningful reductions in knee pain.
The 12 mg group saw a 4.5-point drop on the WOMAC pain scale (a 75.8% reduction), and roughly 1 in 8 participants on retatrutide became completely free of knee pain, compared with 1 in 24 on placebo.4
Cardiometabolic markers improved alongside the weight loss. At the 12 mg dose, systolic blood pressure dropped by 14.0 mmHg, with reductions in non-HDL cholesterol, triglycerides, and high-sensitivity CRP (a marker of inflammation).4
In TRANSCEND-T2D-1, Lilly’s first Phase 3 trial in adults with type 2 diabetes (537 participants, 40 weeks), retatrutide produced 16.8% weight loss at the 12 mg dose.
HbA1c reductions were 1.7% at 4 mg, 2.0% at 9 mg, and 1.9% at 12 mg, compared with 0.8% on placebo.2
Weight loss had not plateaued at 40 weeks, suggesting longer treatment would likely produce more.
Detailed findings are due at the American Diabetes Association Scientific Sessions in June 2026.
Losing and maintaining more than 10% of body weight is associated with significant reductions in obesity-related complications, including hypertension, type 2 diabetes, and heart disease.5
The TRIUMPH trial programme
TRIUMPH is unusual in pharmaceutical development.
Rather than running separate pivotal trials for each indication, Lilly built a basket-trial structure that evaluates retatrutide in obesity alongside two of its common complications: obstructive sleep apnoea (OSA) and knee osteoarthritis. Both conditions are evaluated within the same programme.6
The four core trials:
- TRIUMPH-1 (general obesity, 80 weeks): the largest trial in the programme, with nested OSA and OA protocols. This is the trial that anchors Lilly’s weight-management drug application. Fully published results are expected in the summer of 2026.
- TRIUMPH-2 (obesity with type 2 diabetes, around 1,400 adults): also with nested OSA and OA protocols. Trial results are expected mid-to-late 2026.
- TRIUMPH-3 (obesity with established cardiovascular disease): a higher-risk population. Tests tolerability in the presence of greater comorbidity and provides interim safety data ahead of the longer cardiovascular outcomes trial.
- TRIUMPH-4 (obesity with knee osteoarthritis, no diabetes): reported December 2025, this is the data above.
Running alongside these is TRIUMPH-CVOT, a separate cardiovascular outcomes trial enrolling around 10,000 participants with established cardiovascular disease over 3-4 years.
This is the study regulators will review before granting a broad cardiovascular label, and the one that will ultimately answer the long-term safety question. Published results aren’t expected before 2028.
Retatrutide vs Mounjaro vs Wegovy: how do they compare?
Direct head-to-head trials between retatrutide, tirzepatide, and semaglutide haven’t been completed.
The figures below come from separate trials in different populations, so cross-trial comparisons should be interpreted with caution.
Even so, they give a reasonable sense of how retatrutide compares to other GLP-1 medications.
| Feature |
Retatrutide |
Mounjaro (tirzepatide) |
Wegovy (semaglutide) |
| Mechanism |
Triple agonist (GLP-1 + GIP + glucagon) |
Dual agonist (GLP-1 + GIP) |
Single agonist (GLP-1) |
| Average weight loss |
28.7% over 68 weeks at 12 mg (TRIUMPH-4, obesity + knee OA) |
20.9% over 72 weeks at 15 mg (SURMOUNT-1) |
15% at 2.4 mg over 68 weeks; 18.7% at 7.2 mg over 72 weeks |
| Administration |
Once-weekly injection |
Once-weekly injection |
Once-weekly injection |
| UK approval status (May 2026) |
Not approved; investigational only |
MHRA-approved Nov 2023; NICE TA1026 Dec 2024 |
2.4 mg approved Sep 2021; 7.2 mg approved Jan 2026 |
| NHS availability |
Not available; earliest 2029 |
Available via NHS specialist weight-management services |
Available via NHS specialist weight-management services |
| Private prescription |
Not available legally in the UK |
Available via online pharmacies and weight-loss programmes |
Available via online pharmacies and weight-loss programmes |
| Long-term cardiovascular data |
Pending TRIUMPH-CVOT (expected 2028) |
SURPASS-CVOT due 2025-2026 |
SELECT trial reported 20% reduction in major cardiovascular events |
Is retatrutide the same as tirzepatide (Mounjaro)?
Retatrutide and tirzepatide are different drugs with different chemical structures. Retatrutide mimics three hormones; tirzepatide mimics two.
In the trials we have so far, retatrutide has produced greater weight loss.
The 12 mg dose in TRIUMPH-4 led to a 28.7% loss over 68 weeks, while tirzepatide in the SURMOUNT-1 trial produced approximately 22.5% loss over 72 weeks.1
The cross-trial caveat applies here. SURMOUNT-1 and TRIUMPH-4 enrolled different populations (TRIUMPH-4 included only people with knee osteoarthritis), and direct head-to-head trials comparing retatrutide and tirzepatide haven’t been completed. The headline gap may narrow once like-for-like data is available.
The other practical difference is timing. Tirzepatide is approved and prescribable now, on both the NHS and privately.
Retatrutide, by contrast, is still several years from being available on prescription in the UK, regardless of what the remaining trials show.
Is retatrutide the same as Ozempic (semaglutide)?
Retatrutide and semaglutide (the drug in Ozempic and Wegovy) are different drugs. Semaglutide mimics one hormone (GLP-1); retatrutide mimics three.
Weight loss differs accordingly:
- Wegovy 2.4 mg: around 15% weight loss over 68 weeks.7
- Wegovy 7.2 mg (MHRA-approved January 2026): 18.7% on average over 72 weeks, rising to 20.7% in fully adherent participants, closer to Mounjaro’s results, though still below retatrutide.
- Retatrutide 12 mg: 28.7% over 68 weeks in TRIUMPH-4.
Ozempic isn’t licensed for weight loss in the UK and is only prescribed for type 2 diabetes.
Wegovy is the licensed semaglutide option for weight loss. Retatrutide isn’t approved at all yet, but is expected to be licensed for both indications once trials are complete.
Retatrutide side effects and safety signals
The most common side effects in the Phase 3 trials are gastrointestinal: nausea, vomiting, diarrhoea, and constipation.
In TRIUMPH-4, nausea affected around 43% of participants on 12 mg, vomiting 21%, and diarrhoea 33%. Most cases were mild to moderate and clustered during the dose-escalation period.4
A new safety signal flagged in TRIUMPH-4 is dysaesthesia, an abnormal skin sensation that people describe as burning, tingling, or pins-and-needles.
It affected 8.8% on 9 mg and 20.9% on 12 mg, compared with 0.7% on placebo. Most cases were mild.4
Dysaesthesia isn’t unique to retatrutide. Wegovy 7.2 mg, approved in January 2026, also produces it at high rates (22.9% versus 6.0% at 2.4 mg). At present, this looks like a side effect of high-dose GLP-1-class drugs in general, rather than something specific to retatrutide.
The Phase 2 trial reported small increases in heart rate (around 6.7 beats per minute at 12 mg), peaking around week 24 and then declining.3
Cardiac arrhythmias affected 2-11% of participants on retatrutide versus 2% on placebo, but none were serious. No increase in major cardiovascular events has been reported.
The number of patients stopping the medication due to side effects in TRIUMPH-4 were 18.2% on 12 mg, 12.2% on 9 mg, and 4% on placebo.4
Rates were lower in TRANSCEND-T2D-1: 5.1% at 12 mg, 4.5% at 9 mg, and 2.2% at 4 mg.2
Long-term cardiovascular outcomes data won’t be available until TRIUMPH-CVOT reports, likely in 2028 at the earliest.
When will retatrutide be available?
Retatrutide isn’t approved by the MHRA in the UK or the FDA in the U.S. in May 2026. The realistic timeline is several years away.
Eli Lilly is targeting an FDA new drug application submission in late 2026, after TRIUMPH-1 is published.2
Based on standard FDA review timelines, U.S. approval is plausible from late 2027 onwards.
UK approval typically lags U.S. approval by 6-18 months, putting MHRA approval most realistically in late 2027 to mid-2028.
NHS access then depends on a NICE technology appraisal, which assesses whether the health benefits justify the cost to the NHS.
If the price is high relative to the benefit, NICE can restrict access to specific patient groups (for example, only those with very high BMI or particular comorbidities), or reject NHS use altogether.
The appraisal usually adds 12-18 months to MHRA approval, putting NHS availability in 2029 at the earliest.
For context, here’s how the most recent GLP-1 weight-loss drugs reached UK patients:
- Wegovy (semaglutide 2.4 mg): MHRA approval September 2021, NICE TA875 issued March 2023.8
- Wegovy 7.2 mg: MHRA approval January 2026, NHS access via NICE expected late 2026.
- Mounjaro (tirzepatide): MHRA approval November 2023, NICE TA1026 issued December 2024.9
Retatrutide is also part of a wider pipeline of new weight-loss medications expected over the next 2-3 years. Eli Lilly’s once-daily oral GLP-1, or forglipron, was FDA-approved in April 2026 under the brand name Foundayo.
MHRA approval is expected to follow. For the first time, patients will have a choice between weekly injections and a daily oral tablet, with the triple-agonist retatrutide as the longer-term option behind both.
If retatrutide passes the remaining TRIUMPH trials and is licensed by the MHRA, Second Nature plans to assess it as an option alongside our existing Wegovy and Mounjaro programmes.
Some online vendors sell retatrutide as a “research chemical” or “peptide for research use only.”
These products aren’t regulated by the MHRA and can’t be verified for purity or correct dosing.
In October 2025, the MHRA dismantled the UK’s first illicit weight-loss medicine manufacturing facility, in Northampton, seizing over 2,000 unlicensed retatrutide and tirzepatide pens along with tens of thousands of empty pens ready to be filled.
A second operation in February 2026 disrupted further premises in Lincolnshire.
Counterfeit pens have been found to contain anything from incorrect doses of insulin to other substances, which can cause life-threatening low blood sugar in people who don’t have diabetes.
If you’re considering weight-loss medication now, talk to your GP about MHRA-approved options like Mounjaro and Wegovy.
Second Nature’s published outcomes data shows members on our GLP-1 programmes lose an average of 19.1% of their starting body weight at 12 months, with 77.7% achieving a clinically meaningful loss of 10% or more.10
Frequently asked questions
Can I get retatrutide on the NHS?
No. Retatrutide isn’t approved by the MHRA, so it can’t be prescribed on the NHS or privately in the UK in May 2026.
The earliest realistic date for NHS availability is 2029, after MHRA approval and a NICE technology appraisal.
Is retatrutide better than Mounjaro?
In the trials available so far, retatrutide has produced greater weight loss than tirzepatide (the drug in Mounjaro).
The 12 mg dose led to 28.7% weight loss in TRIUMPH-4, compared with around 22.5% for tirzepatide in SURMOUNT-1.
The two drugs haven’t been compared directly in a head-to-head trial, and the populations studied differ, so the gap may narrow once like-for-like data is available.
How much weight will I lose on retatrutide?
Average weight loss varies by trial population and dose. The Phase 2 trial in general obesity reported 24.2% over 48 weeks at the highest dose.
TRIUMPH-4, in obesity with knee osteoarthritis, reported 28.7% over 68 weeks at 12 mg.
The general obesity Phase 3 figure from TRIUMPH-1 hasn’t been published yet, but is expected to fall between these two.
Is retatrutide safe?
The Phase 2 and Phase 3 trials so far have shown a safety profile broadly consistent with other GLP-1 medications: gastrointestinal side effects are common, and a new signal called dysaesthesia (an abnormal skin sensation) appears more often at higher doses.
Long-term cardiovascular safety won’t be confirmed until TRIUMPH-CVOT reports, expected in 2028 at the earliest.
Is it safe to buy retatrutide online?
No. Retatrutide isn’t licensed in the UK, so any product sold online is unlicensed.
The MHRA dismantled UK-based illicit manufacturing operations producing fake retatrutide and tirzepatide pens in October 2025 and February 2026.
Counterfeit pens have been found to contain incorrect substances, including insulin, which can cause life-threatening low blood sugar in people who don’t have diabetes.
What’s the difference between retatrutide and tirzepatide?
Tirzepatide mimics two hormones (GLP-1 and GIP). Retatrutide mimics three (GLP-1, GIP, and glucagon).
The glucagon component appears to raise the body’s energy use and shift it toward burning stored fat, including liver fat, which is the leading explanation for the larger weight-loss numbers seen with retatrutide in trials.
When will retatrutide be approved in the UK?
A realistic timeline puts MHRA approval in late 2027 to mid-2028, following expected FDA approval in late 2027.
NHS access via NICE is unlikely before 2029. These dates assume the remaining TRIUMPH Phase 3 trials confirm the data seen so far.
Will retatrutide be available privately before the NHS?
Almost certainly yes. UK private prescriptions for both Wegovy and Mounjaro became available shortly after MHRA approval, well before NICE assessed them for NHS use.
Retatrutide is likely to follow the same pattern, with private availability from late 2027 to mid-2028, and NHS access from 2029.
What are the side effects of retatrutide?
The most common side effects in trials are gastrointestinal: nausea (around 43% at 12 mg), vomiting (21%), and diarrhoea (33%).
Most are mild to moderate and improve after the dose-escalation period.
Dysaesthesia (an abnormal skin sensation) affected around 21% of participants at the 12 mg dose. About 18% of participants on the highest dose stopped the medication due to side effects.
Take home message
Retatrutide is the most effective weight-loss medication tested so far, with 28.7% body-weight loss reported at the highest dose in TRIUMPH-4.
The Phase 3 results are promising, but most of the programme is still running, and the long-term cardiovascular outcomes data won’t be available until 2028 at the earliest.
Retatrutide isn’t licensed in the UK and won’t be available on prescription for several years.
A realistic timeline puts MHRA approval in late 2027 to mid-2028, and NHS access via NICE in 2029 at the earliest.
If you’re looking for weight-loss medication now, Mounjaro and Wegovy are both MHRA-approved and produce clinically significant weight loss, with Wegovy 7.2 mg recently approved at the start of 2026.
Avoid any vendor selling retatrutide as a “research peptide” or “research chemical.” These products aren’t regulated, can’t be verified for purity, and the MHRA has dismantled one UK manufacturing operation and disrupted another in the past year.
If retatrutide is licensed by the MHRA in the future, Second Nature plans to assess it as an option alongside our existing Wegovy and Mounjaro programmes.
Second Nature's Mounjaro and Wegovy programmes
Second Nature provides Mounjaro or Wegovy as part of our Mounjaro and Wegovy weight-loss programmes.
Why choose Second Nature over other medication providers, assuming you're eligible?
Because peace of mind matters.
We've had the privilege of working with the NHS for over eight years, helping people across the UK take meaningful steps toward a healthier, happier life.
Our programmes are designed to meet people where they are, whether that means support with weight loss through compassionate one-to-one health coaching, or access to the latest weight-loss medications (like Mounjaro and Wegovy) delivered alongside expert care from a multidisciplinary team of doctors, psychologists, dietitians, and personal trainers.
At the heart of everything we do is a simple belief: real, lasting change comes from building better habits, not relying on quick fixes. We're here to support that change every step of the way.
With over a decade of experience, thousands of lives changed, and a long-standing record of delivering programmes used by the NHS, we believe we're the UK's most trusted weight-loss programme.
We hope to offer you something invaluable: peace of mind, and the support you need to take that first step.
References
- Eli Lilly. (2025). Lilly’s triple agonist retatrutide delivered weight loss of an average of 28.7% in TRIUMPH-4.
- Eli Lilly. (2026). Lilly’s triple agonist, retatrutide, demonstrated significant reductions in A1C and weight in first Phase 3 trial for treatment of type 2 diabetes (TRANSCEND-T2D-1).
- Jastreboff, A. M., Kaplan, L. M., Frías, J. P., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity. A Phase 2 Trial. New England Journal of Medicine, 389(6), 514-526.
- Eli Lilly Medical. (2025). Preliminary results with retatrutide from TRIUMPH-4 in participants with obesity or overweight and osteoarthritis.
- Garvey, W. T., Mechanick, J. I., Brett, E. M., et al. (2016). AACE/ACE Comprehensive Clinical Practice Guidelines for Medical Care of Patients with Obesity. Endocrine Practice, 22(Suppl 3), 1-203.
- Giblin, E. M., et al. (2026). Retatrutide for the treatment of obesity, obstructive sleep apnoea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials. Diabetes, Obesity and Metabolism.
- Wilding, J. P. H., et al. (2021). Once-weekly semaglutide in adults with overweight or obesity. New England Journal of Medicine, 384, 989-1002.
- National Institute for Health and Care Excellence. (2023). TA875: Semaglutide for managing overweight and obesity.
- National Institute for Health and Care Excellence. (2024). TA1026: Tirzepatide for managing overweight and obesity.
- Richards, R., et al. (2025). A Remotely Delivered GLP-1RA-Supported Specialist Weight Management Program in Adults Living With Obesity: Retrospective Service Evaluation. JMIR Formative Research.
Note on Phase 3 sources: Topline results for TRIUMPH-4 (announced December 2025) and TRANSCEND-T2D-1 (announced March 2026) are sourced from Eli Lilly’s primary disclosures. Full peer-reviewed publications are pending. TRANSCEND-T2D-1 detailed results are scheduled for the American Diabetes Association Scientific Sessions in June 2026. Trial registry entries: NCT05931367 (TRIUMPH-4) and NCT06354660 (TRANSCEND-T2D-1). This article will be updated when peer-reviewed publications become available.
