Retatrutide: What It Is and What the Trials Show

Retatrutide is a new weight-loss and metabolic compound made by Eli Lilly. It still goes by its lab code, LY3437943, because it has not been approved or given a brand name yet.

You have probably heard of semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). Retatrutide comes from the same family, but it works on one more hormone than either of them. In trials it has produced the biggest weight loss of any non-surgical treatment so far.

Weight is only part of the story. The 2026 trial papers show improvements across blood sugar, liver fat, blood pressure, cholesterol, kidneys, joints and sleep. This guide covers all of it in plain language, with the source for every number.

What does retatrutide actually do for you?

Here is what a course is usually like, in everyday terms.

• The first week. Appetite drops within 1 to 3 days. Mild nausea is common at the start.
• Weeks 2 to 4. Stomach side effects are at their worst as the dose steps up. Weight loss is still modest at this stage.
• Weeks 4 to 12. Once the dose is steady, the stomach side effects ease and your appetite stays low.
• Long term. In the trials, weight kept coming off without stalling, out to 80 weeks and beyond on the top dose.

What not to expect: a permanent fix. With drugs in this family, most people regain a good part of the weight after they stop. Eating enough protein and doing some strength training matters too, because some of the weight lost is muscle.

Two things are more noticeable than with tirzepatide. Your resting heart rate goes up a little. And some people get odd skin sensations, like tingling or extra sensitivity, mostly on the top dose and usually mild. The side effects section below has the numbers.

What is retatrutide?

Retatrutide is a peptide, a short chain of amino acids, given as a small injection once a week. It copies three hormones your body already releases around meals:

• GLP-1 tells your brain you are full and slows down how fast your stomach empties.
• GIP helps your body handle sugar and seems to make GLP-1 easier to tolerate.
• Glucagon acts on the liver and on how your body uses stored fat.

Here is how it compares with the two you may already know:

That is why it is called a "triple agonist". An agonist is something that switches a receptor on, and retatrutide switches on three. It is one molecule doing all three jobs, not a blend. For a full side-by-side, see Retatrutide vs Tirzepatide vs Semaglutide.

How does retatrutide work?

Retatrutide works on both sides of the weight equation. Your weight comes down to energy in (what you eat) and energy out (what your body uses).

Energy in. The GLP-1 and GIP parts turn down hunger and the constant thinking about food that many people call "food noise". You feel full sooner and stay full longer. This is the same engine that drives semaglutide and tirzepatide.

Energy out and the liver. The glucagon part is what makes retatrutide different. In lab and animal studies, glucagon helps the body break down stored fat and clear fat out of the liver, and it can raise the energy the body burns. The liver results in humans are striking (more on that below). The extra calorie burn has been shown in animal studies, but human data on it has not been published yet.

Lilly balanced the three hormones on purpose. According to Coskun et al. 2022, retatrutide leans strongly on GIP and keeps the glucagon effect mild, so it gets the fat-burning and liver benefits without pushing blood sugar up.

How much weight do people lose on retatrutide?

In the biggest trials, people lost between a fifth and nearly a third of their body weight. That is the strongest result yet for a medicine rather than surgery.

• TRIUMPH-1 (Phase 3, people with obesity, NEJM, Sep 2026): 25% average weight loss at 80 weeks on 12 mg, against 3.9% on placebo. Among people who kept taking it as planned, the figure was 28.3%. By two years it reached 29.9%.
• TRIUMPH-2 (Phase 3, people with obesity and type 2 diabetes, Lancet, Sep 2026): 18.8% at 80 weeks against 5.1% on placebo. People with diabetes usually lose less weight on every drug in this class, so this is a strong result for that group.
• TRIUMPH-4 (Phase 3, obesity plus knee arthritis, Lilly, Dec 2025): 28.7% at 68 weeks. This is Lilly's announced result; the full paper is still to come.
• Phase 2 (Jastreboff et al. 2023): 24.2% at 48 weeks on 12 mg, and weight was still falling when the trial ended.

Two things are worth knowing. Results depend on the dose: 4 mg produced less than 9 or 12 mg. And trial numbers come from closely supervised dosing, so results in everyday life can be a bit lower.

What does retatrutide do beyond weight loss?

This is where retatrutide gets really interesting. Losing a lot of weight improves health on its own, but the trials measured much more than the scale. Across blood sugar, liver fat, blood pressure, cholesterol, inflammation, kidneys, joints and sleep, people on retatrutide improved far more than people on placebo.

Some changes show up early. Most of the liver fat was gone by 24 weeks, and blood sugar targets were reached within 40 weeks. Others keep building over the long term, and weight, waistline, blood pressure and joint pain were still improving at 80 weeks and beyond.

Here is the summary first, then the detail.

Blood sugar and prediabetes

This is one of the strongest results in the whole program.

• Prediabetes reversed. In TRIUMPH-1, about a third of people started with prediabetes. On retatrutide, 89 to 93% of them had normal blood sugar by 80 weeks, compared with 54% on placebo (NEJM 2026).
• Early type 2 diabetes. In TRANSCEND-T2D-1, people with recently diagnosed diabetes and no other diabetes medicine saw their HbA1c (a measure of average blood sugar over about three months) fall by up to 1.94 points in 40 weeks. Up to 89% reached the usual HbA1c target of under 7%, against 52% on placebo. Up to 40% got all the way into the normal, non-diabetic range (Lancet 2026). There were no cases of severe low blood sugar.
• Insulin. Fasting insulin dropped by about half in TRIUMPH-1 (down 52 to 55%, against 11% on placebo). Lower fasting insulin is a sign the body is responding to insulin better.
• Longer-standing diabetes. In TRIUMPH-2, about 72% of people with type 2 diabetes reached an HbA1c of 6.5% or lower, against 29% on placebo (Lancet 2026).

Liver fat

Fatty liver (now called MASLD) is very common in people carrying extra weight, and it rarely causes symptoms until it is advanced. This is where the glucagon part of retatrutide stands out.

In a Phase 2 study of 98 people with fatty liver (Sanyal et al. 2024, Nature Medicine), liver fat measured by MRI fell by 82% in 24 weeks on 12 mg, and by 86% at 48 weeks. Placebo showed no change. By 48 weeks, 93% of people on the top dose had a normal amount of liver fat.

Bigger trials are now testing whether this protects the liver over the long run. Lilly's liver outcomes trial (SYNERGY-Outcomes) is running until about 2030.

Heart health markers

Retatrutide improved almost every blood marker linked to heart disease.

• Blood pressure: systolic pressure (the top number) fell by 10.4 mmHg on 12 mg in TRIUMPH-1, against 1.9 on placebo. In the Phase 2 trials, 30 to 41% of people on the higher doses came off at least one blood pressure medicine (Heerspink et al. 2025).
• Triglycerides (a type of blood fat): down 38%, against 3% on placebo.
• Cholesterol: non-HDL cholesterol (all the "bad" kinds together) fell by about 21%, and LDL by about 20% (ADA 2026 slides).
• The particles that clog arteries: a 2026 analysis found ApoB down 24%, remnant cholesterol down 39% and small dense LDL particles down 32% (Diabetes Obes Metab, Aug 2026). These are some of the most closely watched markers of artery risk.
• Inflammation: hsCRP, a blood marker of body-wide inflammation, fell by 63%, against 25% on placebo.

What these markers mean for actual heart attacks and strokes is being tested in TRIUMPH-Outcomes, a trial of about 10,000 people that is due to finish in 2029 (NCT06383390).

Kidneys

In TRIUMPH-2, people with type 2 diabetes on retatrutide saw their eGFR (a measure of how well the kidneys filter) go up by about 5 points, while it stayed flat on placebo. Protein leaking into the urine, an early sign of kidney strain, also trended down. The Phase 2 trials showed it falling by about a third (Heerspink et al. 2025). Researchers are still working out how much of the filtration rise is lasting, and a dedicated kidney trial (TRANSCEND-CKD) has finished but not yet reported.

Joints: knee arthritis pain

Carrying less weight takes load off the knees, and the trials measured it directly.

• In TRIUMPH-1, people with knee osteoarthritis rated their pain about 6 out of 10 at the start. On retatrutide it fell by 3.6 points in 80 weeks, against 1.9 on placebo.
• In TRIUMPH-4, pain scores fell by 4.4 points against 2.4 on placebo, physical function improved, and 12% became completely pain-free, against 4% on placebo (Lilly, Dec 2025).

Sleep apnoea

Obstructive sleep apnoea is when breathing keeps stopping during sleep, which leaves people exhausted and strains the heart. In TRIUMPH-1, people with moderate to severe sleep apnoea started at about 59 breathing pauses an hour. On retatrutide that fell by about 32 an hour, a reduction of up to 57%, against about 10 on placebo.

Waistline, body fat and everyday life

• Waist: down 21.6 cm on average in TRIUMPH-1, against 4.6 cm on placebo. Waist size tracks the deep belly fat around the organs, which matters most for health.
• Body fat: in a body-scan study, about two-thirds of the weight lost was fat (Coskun et al. 2025). That is similar to other drugs in the class (see the note on muscle under side effects).
• Quality of life: people's scores for physical function and day-to-day wellbeing improved about twice as much as on placebo. The improvements included how easily they could move, work and get through the day.

What is still to come

Retatrutide is still in trials, so some answers are not in yet. The heart outcomes trial reports in 2029 and the liver outcomes trial around 2030. Head-to-head trials against tirzepatide and semaglutide are also underway. So far, each new Phase 3 trial has confirmed the weight and health-marker results above.

How is retatrutide dosed?

Retatrutide is injected once a week, just under the skin, and the dose is raised slowly over several months.

In the trials, people started at 2 mg and stepped up every four weeks: 2, then 4, 6, 9 and finally 12 mg. Some stayed at 4 or 9 mg instead of going all the way. These are the doses used to get the maximum trial results, not a starting point for everyone.

Going slowly matters. In Phase 2, starting at 2 mg instead of 4 mg cut early nausea from 60% to 17% at the 8 mg step. The speed of the increase is the biggest single factor in how well people tolerate it.

In the community, people usually go even gentler. A common pattern is to start at about 0.25 to 0.5 mg a week, hold each step for two to four weeks, and settle somewhere between 1.5 and 4 mg a week. Many split the weekly dose into two smaller injections (for example half on Monday, half on Thursday) to smooth out side effects. These are community habits, not tested protocols.

On microdosing: some people use small weekly doses for appetite and liver-fat goals rather than big weight loss. Just know that a small dose gives a smaller effect. In Phase 2, the 1 mg group lost 8.7% at 48 weeks, against 24.2% on 12 mg.

Retatrutide comes as a dry powder that you mix with bacteriostatic (BAC) water before use. If you are new to this, our guide on how to reconstitute and dose walks you through it step by step.

Mixing this yourself? Our mixing guide has the exact bacteriostatic-water volume and dose-per-unit for every product.

What are the side effects of retatrutide?

Most side effects are stomach-related, depend on the dose, and are worst while the dose is going up. They usually settle once the dose is steady.

• Nausea is the most common. In TRIUMPH-1 it affected 42% of people on 12 mg at some point, against 15% on placebo. Vomiting (25% against 5%), diarrhoea and constipation follow the same pattern. Raising the dose slowly is the main way to keep these down.
• Skin sensations. Some people feel tingling, burning or extra sensitivity on the skin (doctors call it dysaesthesia). In TRIUMPH-1 it affected 12.5% on 12 mg, against 1% on placebo, and it was higher in TRIUMPH-4 (21%). It was mostly mild, and most cases cleared up while people kept taking it.
• Heart rate. Resting heart rate went up a little on the higher doses, peaked around week 20, then eased back. Serious heart rhythm problems were not more common than on placebo in TRIUMPH-1.
• Dizziness and low blood pressure. Because retatrutide lowers blood pressure, some people felt dizzy, especially those already taking blood pressure medicine. If that is you, it is worth keeping an eye on your readings.
• Stopping because of side effects: about 11% of people on 12 mg in TRIUMPH-1, against about 4% on placebo.
• Rare but serious: pancreatitis and gallbladder problems are possible with every drug in this class. The class also carries a thyroid warning based on rodent studies; no human cases have been reported.

Protect your muscle. When you lose a lot of weight quickly, some of it is muscle. In the body-scan study about two-thirds of the loss was fat and one-third lean tissue, which is in line with the other drugs. Eating enough protein and doing some resistance training are the usual ways to hold on to muscle while the weight comes off.

Who is retatrutide for?

Research and community interest in retatrutide mostly comes from people who:

• Want a large amount of weight off, especially if tirzepatide or semaglutide has stopped working for them (people call this the "Tirz plateau").
• Care about more than the scale: fatty liver, blood sugar, blood pressure, triglycerides, joint pain or sleep.
• Like the simplicity of once a week, with little to manage day to day.
• Use a low dose mainly to quiet food noise and support liver health rather than chase maximum weight loss.

It is a less natural fit if you want a medicine with a long approval history (tirzepatide has more years behind it), or if you are not able to keep up protein intake and some strength training.

What is the food-noise and cravings research?

"Food noise" is the constant background chatter about what and when to eat next. Quieting it is one of the best-known effects of this whole family of drugs. Many people describe feeling calmer around food and having more headspace for other things.

Researchers are also looking at whether these drugs reduce other cravings, such as alcohol and nicotine, because they act on the brain's reward system. That work is early and has not been confirmed for retatrutide specifically. A few people report the flip side, feeling a bit less driven or a lower libido at higher doses.

What should you know before starting?

It is not approved yet. Retatrutide is still in clinical trials. Lilly plans to apply for FDA approval in early 2027. Until then it is supplied as a research compound.

Long-term results are still coming. The trials so far run up to about two years. The large heart and liver outcome trials report in 2029 and around 2030.

Weight can come back after stopping. This has been seen across the whole class. After stopping semaglutide, people regained about two-thirds of the weight they had lost within a year (Wilding et al. 2022), and tirzepatide showed a similar pattern (Aronne et al. 2023). Building eating and training habits while the weight comes off is what helps keep it off.

How does retatrutide compare across the range?

On the trial numbers, retatrutide leads on total weight loss and on the wider health markers, especially liver fat. Tirzepatide's strengths are that it is already FDA-approved, has more years of safety data and slightly stronger appetite control milligram for milligram. Both are reasonable places to start, and you do not need to "work up" to retatrutide from something milder first.

The full case for tirzepatide is in the Tirzepatide deep-dive. Primogen does not stock semaglutide, because the two newer options lead it on the data.

Referenced products

Retatrutide

from Rp 2.590.000