Retatrutide 20 mg

Retatrutide — 10 / 20 mg

Purity: ≥98% (HPLC) Form: lyophilized powder, 3 ml vial Storage: −20 °C (before opening), +2…+8 °C (after reconstitution, no more than 28 days) Verification: Janoshik Analytical (Czech Republic) — independent blind test of every batch Synonyms: Retatrutide, LY3437943, Retatrutide Developer: Eli Lilly and Company (USA) Status: Phase 3 (TRIUMPH program), not FDA approved

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Contents

1. What is Retatrutide?
2. Why Retatrutide attracts researchers' attention
3. Peptide structure
4. Three receptors — in simple terms
5. Clinical research results
6. Retatrutide and liver fat tissue
7. The TRIUMPH program — Phase 3
8. How Retatrutide differs from Tirzepatide
9. Sources

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1. What is Retatrutide?

Retatrutide is a next-generation research peptide developed by Eli Lilly. It is the first triple agonist in history: it acts simultaneously on three receptors — GLP-1, GIP, and glucagon. For comparison: semaglutide acts on one receptor, tirzepatide on two. Retatrutide acts on all three.

The peptide is administered subcutaneously once a week (half-life — about 6 days). It is in Phase 3 of clinical research — the final stage before possible approval by regulators.

For research use only. Not a medicinal product. Not intended for use in humans or animals.

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2. Why Retatrutide attracts researchers' attention

In short — because in clinical research it has shown results that exceeded all previous peptides of its class:

• −24.2% body weight over 48 weeks in a Phase 2 study published in the New England Journal of Medicine — one of the most authoritative medical journals in the world [1]. And at the time the study ended, the reduction had not stopped — a plateau had not been reached.

• −28.7% body weight over 68 weeks in the Phase 3 study TRIUMPH-4, according to an Eli Lilly press release [5]. That is on the order of 30 kg for a person weighing 105 kg.

• −82% liver fat in a Phase 2 substudy published in Nature Medicine [3]. Non-alcoholic fatty liver disease is one of the actively studied areas of metabolic research.

• The third receptor — the glucagon receptor. It is precisely this that distinguishes retatrutide from tirzepatide. Glucagon increases energy expenditure and stimulates fat oxidation — a mechanism that the previous generation of peptides does not have.

All of the data listed above were obtained within controlled clinical research with placebo groups. The peptide is not approved by regulators and is not a medicinal product.

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3. Peptide structure

Parameter	Value
Type	Synthetic peptide, triple agonist GIP/GLP-1/GCG
Development code	LY3437943
Developer	Eli Lilly and Company
Administration	Subcutaneous injection, once a week
Half-life	~6 days
Molecular profile	Peptide conjugated with a fatty-acid fragment (C20 fatty diacid)
Activity relative to endogenous ligands	GIP — 8.9× more potent, GLP-1 — 0.4×, GCG — 0.3× [4]

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4. Three receptors — in simple terms

To understand why retatrutide generates such interest, it is worth examining its three-receptor mechanism.

GLP-1 (glucagon-like peptide-1). Your gut produces it after every meal. It sends the brain a signal: "Enough, you are full." It also slows gastric emptying — food is digested for longer, and the feeling of satiety lasts longer. It is precisely on this receptor that semaglutide works.

GIP (glucose-dependent insulinotropic peptide). The second satiety hormone. It enhances the effect of GLP-1, improves insulin sensitivity, and participates in fat processing. Tirzepatide became the first peptide to engage both receptors — GLP-1 and GIP.

Glucagon. The third receptor — and the key difference of retatrutide. Glucagon is a hormone that ramps up energy expenditure: the body begins to "burn" reserves more actively. While GLP-1 and GIP reduce energy intake (you eat less), glucagon increases expenditure (you spend more). Researchers describe this as a "pharmacological triangle": reduced intake + improved metabolism + increased expenditure [6].

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5. Clinical research results

Phase 2 — obesity (NEJM, 2023)

Key study: 338 participants with BMI ≥30 (or ≥27 in the presence of comorbidities), 48 weeks, randomized, double-blind, placebo-controlled [1].

Results by dose:

Dose	Body weight reduction	Proportion losing ≥15%
4 mg	−8.7%	~25%
8 mg	−17.1%	~63%
12 mg	−24.2%	~83%
Placebo	−2.1%	~4%

A plateau was not reached — the curve continued to decline toward week 48.

Phase 2 — type 2 diabetes (Lancet, 2023)

282 participants, 36 weeks [2]. HbA1c reduction up to −2.2%, body weight reduction up to −16.9%. 82% of participants achieved HbA1c ≤6.5%.

Phase 3 — TRIUMPH-4 (2025)

The TRIUMPH program is a series of Phase 3 studies by Eli Lilly [5]. TRIUMPH-4 (68 weeks, obesity + knee osteoarthritis): body weight reduction up to −28.7%.

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6. Retatrutide and liver fat tissue

Of separate interest is the effect of retatrutide on liver fat tissue. In a Phase 2 substudy published in Nature Medicine, liver fat content was assessed in participants with metabolic dysfunction-associated steatotic liver disease (MASLD) [3].

Result: liver fat content reduction up to −82% at the 12 mg dose over 48 weeks. Researchers associate this with the glucagon component of retatrutide — activation of the glucagon receptor in the liver enhances fatty acid oxidation.

This direction represents significant scientific interest, since at the time of publication no drug for the treatment of MASH (formerly NASH) had been approved in either the USA or Europe.

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7. The TRIUMPH program — Phase 3

Retatrutide is in the final stage of clinical research. The TRIUMPH program includes several parallel studies:

Study	Population	Status
TRIUMPH-1	Obesity without diabetes	Phase 3
TRIUMPH-2	Obesity + type 2 diabetes	Phase 3
TRIUMPH-3	Maintenance of achieved weight reduction	Phase 3
TRIUMPH-4	Obesity + osteoarthritis	Completed, results published
TRANSCEND-T2D-1	Type 2 diabetes, monotherapy	Phase 3, completed [7]

If the Phase 3 results confirm the Phase 2 data, retatrutide may become the first triple agonist approved by regulators.

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8. How Retatrutide differs from Tirzepatide

Parameter	Semaglutide	Tirzepatide	Retatrutide
Receptors	GLP-1	GLP-1 + GIP	GLP-1 + GIP + Glucagon
Type	Mono-agonist	Dual agonist	Triple agonist
Max. weight reduction (Phase 2/3)	~15–17%	~22.5%	~24.2–28.7%
Effect on energy expenditure	No	No	Yes (via glucagon)
Effect on liver fat	Moderate	Significant	Up to −82%
FDA status	Approved	Approved	Phase 3

All three peptides are successive generations of one class. Each subsequent one adds a new mechanism. Retatrutide is the newest and is studied as the most comprehensive of those that exist.

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Sources

1. Jastreboff A.M. et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N. Engl. J. Med., 389: 514–526, 2023. PubMed

2. Rosenstock J. et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial. Lancet, 402(10401): 529–544, 2023. PubMed

3. Sanyal A.J. et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Nat. Med., 30: 2037–2048, 2024. PubMed

4. Coskun T. et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: from discovery to clinical proof of concept. Cell Metab., 34(9): 1234–1247, 2022. PubMed

5. Eli Lilly press release: TRIUMPH-4 Phase 3 Results. investor.lilly.com, 2025.

6. Nauck M.A. et al. Triple Agonism Based Therapies for Obesity. Curr. Obes. Rep., 2025. PMC

7. Frias J.P. et al. Efficacy and safety of retatrutide in people with type 2 diabetes (TRANSCEND-T2D-1): a phase 3 trial. Lancet, 2026. ScienceDirect

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This material was prepared by the LONGIVIYA editorial team based on published scientific research. The information is for educational purposes only and is not a medical recommendation.

For research use only. Not a medicinal product. Not intended for use in humans or animals. Independent verification of every batch: Janoshik Analytical (Czech Republic).