What is Retatrutide?
Retatrutide (development code LY3437943) is a single lipidated peptide of 39 amino acids with a molar mass of about 4731 g/mol, designed by Eli Lilly. Like tirzepatide it starts from a GIP-like backbone, uses non-natural residues to resist rapid enzymatic breakdown, and carries a C20 fatty diacid that binds plasma albumin for a long half-life.
What makes it different is the third target. Besides the two incretin receptors that drive appetite and insulin signals, retatrutide also stimulates the glucagon receptor, which in the liver is linked to fat burning and energy expenditure. The combination is why it is often called a triple agonist or triple G, and why liver fat is one of its most striking research readouts.
Retatrutide is not an approved medicine. As of September 2026 it has completed several phase 3 trials in obesity, type 2 diabetes and knee osteoarthritis, with more of the TRIUMPH and TRANSCEND programmes still reporting.
Benefits of Retatrutide reported in research
Evidence level shown on each card.Record weight loss in phase 3
In TRIUMPH-1, 2,339 adults with obesity or overweight lost 19.0 %, 25.9 % and 28.3 % of body weight across three dose groups at 80 weeks, versus 2.2 % on placebo (efficacy estimand). At the highest dose, 45.3 % of participants lost 30 % or more.
Up to 24.2 % weight loss in under a year
In the 48-week phase 2 trial (NEJM, 2023), weight fell by up to 24.2 % versus 2.1 % on placebo, and every participant in the highest dose group lost at least 5 % of body weight.
Clears liver fat
In a phase 2a substudy in people with fatty liver disease (Nature Medicine, 2024), liver fat fell by up to 82.4 % in 24 weeks, and 86 % of participants in the highest dose group reached normal liver fat below 5 %, versus 0 % on placebo.
Lower blood sugar in type 2 diabetes
In the phase 3 TRANSCEND-T2D-1 trial (Lancet, 2026), retatrutide alone reduced HbA1c by up to 1.94 percentage points and body weight by up to 15.3 % over 40 weeks, compared with 0.81 points and 2.6 % on placebo.
Less knee osteoarthritis pain
In the phase 3 TRIUMPH-4 trial in 445 adults with obesity and knee osteoarthritis, announced in December 2025, retatrutide produced up to 28.7 % weight loss at 68 weeks together with a marked reduction in WOMAC knee pain scores compared with placebo.
What the research shows
The phase 2 obesity study (Jastreboff et al., New England Journal of Medicine, 2023) enrolled 338 adults and tested six dose arms against placebo for 48 weeks. Weight loss was dose-dependent: at 48 weeks, 83 % of the highest dose group had lost 15 % or more of body weight, compared with 2 % on placebo. Gastrointestinal events were the most common side effects and were reduced with a lower starting dose.
A companion phase 2 trial in type 2 diabetes (Rosenstock et al., Lancet, 2023) compared retatrutide with placebo and dulaglutide in 281 adults over 36 weeks, reporting meaningful reductions in both HbA1c and body weight. The liver substudy (Sanyal et al., Nature Medicine, 2024) found that liver fat reductions tracked improvements in insulin sensitivity and lipid metabolism, in line with the extra glucagon-receptor activity.
Phase 3 results began in December 2025 with TRIUMPH-4 in knee osteoarthritis, followed in May 2026 by TRIUMPH-1, the pivotal obesity study. In its 104-week extension, participants with a BMI of 35 or more in the highest dose group reached an average loss of 30.3 %. The TRANSCEND-T2D-1 monotherapy trial in 537 adults with type 2 diabetes was published in The Lancet in 2026.
In the lab, retatrutide is used to study how glucagon-receptor activity adds to incretin signalling, particularly in liver lipid handling and energy expenditure models, and to benchmark it against dual agonists such as tirzepatide.
Retatrutide - frequently asked questions
What is retatrutide?
+
Retatrutide is an investigational peptide from Eli Lilly that activates the GIP, GLP-1 and glucagon receptors with one molecule. It is 39 amino acids long and carries a fatty-acid chain that binds albumin for long-lasting action. It is in phase 3 clinical trials and has not been approved as a medicine.
How much weight loss did retatrutide show in trials?
+
In the phase 3 TRIUMPH-1 trial, adults with obesity lost an average of 28.3 % of body weight at the highest dose after 80 weeks, versus 2.2 % on placebo. In the earlier 48-week phase 2 trial, the highest dose produced 24.2 % average weight loss.
Retatrutide vs tirzepatide: what is the difference?
+
Tirzepatide activates two receptors, GIP and GLP-1, while retatrutide adds a third, the glucagon receptor, which is linked to liver fat reduction and higher energy expenditure. Tirzepatide is an approved medicine; retatrutide is still investigational. The two have not yet been compared in a published head-to-head trial.
Is retatrutide FDA or EMA approved?
+
No. As of September 2026, retatrutide is not approved by the FDA, the EMA or any other major regulator. Several phase 3 TRIUMPH and TRANSCEND trials have reported positive results, which are expected to support future regulatory submissions.
How should retatrutide be stored in the lab?
+
Lyophilized retatrutide should be stored sealed at -20 °C for long-term stability and at 2-8 °C for short periods, protected from light and moisture. Solutions are less stable than the powder and should be kept cold and not refrozen repeatedly.
