Retatrutide (LY3437943) is an investigational peptide and triple receptor agonist — meaning it activates three hormone receptors at once: GLP-1, GIP, and glucagon receptors.[5] It is being studied in clinical trials for obesity and metabolic conditions.[1] It is not approved for human use and is classified as a research compound only.[4]

How does Retatrutide work?

Retatrutide simultaneously activates three receptors. The GLP-1 and GIP receptors reduce appetite and slow gastric emptying. The glucagon receptor boosts energy expenditure — essentially turning up the body's calorie-burning rate. In animal studies, this glucagon-driven energy increase added extra weight loss on top of the appetite suppression from the other two receptors.[5] This triple action is what sets it apart from earlier single- or dual-agonist compounds.[4]

What is Retatrutide used for in research?

Researchers are primarily studying retatrutide for obesity and type 2 diabetes. Early trials also observed signals of benefit for fatty liver disease (hepatic steatosis) and diabetic kidney disease.[4] It is part of a broader wave of next-generation incretin-based medicines being explored for cardiometabolic conditions.[2] Phase 3 TRIUMPH trials are ongoing to evaluate long-term safety and efficacy.[4]

How is Retatrutide dosed in research studies?

In the key Phase 2 trial, retatrutide was given as a once-weekly subcutaneous injection with a gradual dose titration — starting at 2 mg/week to minimize side effects, then stepping up over weeks toward maintenance and higher doses.[1] See the dosage chart and calculator on this page for the specific schedule used in trials. These numbers come from research protocols, not prescribing guidelines.

How do you reconstitute Retatrutide for research use?

Research-grade retatrutide powder is typically dissolved in bacteriostatic water for injection. Inject the water gently down the vial wall and swirl — never shake — to dissolve. Store the reconstituted solution refrigerated at 2–8 °C and use within approximately 28 days. Always inspect for clarity before use and discard any cloudy or particulate solution. Follow your specific research protocol for concentration calculations.

Is Retatrutide safe? What side effects were seen in trials?

In the Phase 2 trial, the most common side effects were gastrointestinal — nausea, vomiting, and similar issues — and they were dose-dependent (more common at higher doses).[1] These were mostly mild to moderate. Starting at a lower 2 mg dose rather than 4 mg helped reduce them.[1] Dose-dependent increases in heart rate were also observed, peaking at 24 weeks and declining afterward.[1] Long-term safety data from Phase 3 trials is still pending.[4]

Retatrutide Dosage Chart, Protocol & Calculator

An investigational triple-agonist studied for weight and metabolic outcomes.

Goal	Dose	Frequency	Duration	Evidence	Source
Titration start	2 mg	1×/week	weeks 1–4	Clinical	PMID 37366315
Mid maintenance	4–8 mg	1×/week	weeks 5–12	Clinical	PMID 37366315
High dose (studied)	12 mg	1×/week	per trial	Clinical	PMID 37366315

What is Retatrutide?

Retatrutide — also called LY3437943 — is an investigational peptide developed by Eli Lilly. It belongs to a cutting-edge class sometimes called triple agonists because it activates three different hormone receptors at the same time: the GLP-1 receptor, the GIP receptor, and the glucagon receptor.^[5] No approved drug currently hits all three targets together, which is why retatrutide is generating so much excitement in metabolic research.^[4] It is not approved for human use — it is strictly a research compound being studied in clinical trials.

How Retatrutide Works

Think of your body's appetite and metabolism like a thermostat with three dials. Most older drugs only turn one dial. Retatrutide turns all three at once:

GLP-1 receptor: Slows the stomach down and signals the brain to feel full, reducing how much you eat.^[5]
GIP receptor: Another gut hormone that helps manage insulin release and energy storage — activating it seems to enhance weight-loss signals even further.^[5]
Glucagon receptor: Glucagon is famous for raising blood sugar, but activating its receptor also turns up the body's calorie-burning furnace (energy expenditure). Retatrutide's glucagon activity adds a fat-burning boost on top of the appetite suppression from the other two receptors.^[5]

In simple terms: retatrutide makes you eat less and burn more at the same time — a combination that researchers believe explains its unusually strong effects in early trials.^[4]

What the Research Shows

The most important human data so far comes from a Phase 2 clinical trial published in the New England Journal of Medicine in 2023.^[1] Researchers enrolled 338 adults with obesity and randomly assigned them to different weekly doses of retatrutide or placebo for 48 weeks.

The results were striking. At 48 weeks, participants in the highest-dose group (12 mg/week) lost an average of 24.2% of their body weight — compared with just 2.1% in the placebo group.^[1] Even at the 8 mg dose, average weight loss hit 22.8%.^[1] To put that in perspective: 100% of participants in the 8 mg and 12 mg groups lost at least 5% of their body weight, and 83% of the 12 mg group lost 15% or more.^[1]

A 2025 systematic review of emerging obesity pharmacotherapies confirmed that completed Phase 2 trials on incretin-based drugs like retatrutide showed mean weight losses ranging from 7.4% to 24.2%, with retatrutide sitting at the very top of that range.^[3] Researchers also observed improvements in blood sugar control and markers of liver fat.^[4]

The earlier discovery paper, published in Cell Metabolism in 2022, showed that in obese mice, retatrutide decreased body weight and improved blood sugar — and that the glucagon component specifically added extra weight loss by boosting energy expenditure on top of reduced calorie intake.^[5] A Phase 1 human study in that same paper showed a pharmacokinetic profile that supported once-weekly dosing, and weight loss was still detectable 43 days after just a single dose.^[5]

Retatrutide is also being discussed as part of the broader wave of next-generation GLP-1-based medicines that are being explored for conditions well beyond obesity, including metabolic liver disease and kidney disease.^[2]

What Retatrutide Is Being Studied For

Obesity — the primary focus of Phase 2 and ongoing Phase 3 (TRIUMPH) trials^[4]
Type 2 diabetes — improvements in HbA1c (a long-term blood sugar marker) were seen in early trials^[4]
Liver steatosis (fatty liver disease) — early signals of benefit observed^[4]
Diabetic kidney disease — under active investigation^[4]
General cardiometabolic health — part of the wider incretin research landscape^[2]

How Retatrutide Is Dosed in Research

In clinical trials, retatrutide is administered as a once-weekly subcutaneous (under-the-skin) injection.^[1] Researchers used a gradual titration approach — starting low and stepping up over weeks — specifically to reduce gastrointestinal side effects, which were found to be partially mitigated by beginning at a lower starting dose of 2 mg rather than jumping straight to a higher dose.^[1] The full breakdown of the titration schedule used in studies — including the starting dose, mid-range maintenance doses, and the highest dose studied — is laid out in the dosage chart on this page. You can also use the calculator on this page to explore weight-based reference figures. Remember: these figures come from research protocols and are not prescribing instructions.

Mixing and Storing Retatrutide

In research settings, retatrutide peptide is typically supplied as a lyophilized powder (freeze-dried) that must be reconstituted — that is, dissolved in a liquid — before use. The standard diluent is bacteriostatic water for injection (sterile water with a small amount of benzyl alcohol as a preservative, which helps the solution last longer in the vial). Here are the general research-use basics:

Reconstitution: Inject the bacteriostatic water slowly down the side of the vial — never shoot it directly onto the powder. Gently swirl; do not shake vigorously, as peptides can degrade.
Concentration: Researchers typically target a concentration that keeps individual injection volumes practical (often 1–2 mg/mL), but the exact calculation depends on the amount of powder in the vial.
Storage before mixing: Keep lyophilized peptide refrigerated (2–8 °C / 36–46 °F) and away from light.
Storage after mixing: Reconstituted solution should be kept refrigerated and is generally used within 28 days. Avoid repeated freeze-thaw cycles.
Inspection: Always inspect the solution before use — it should be clear and free of particles. Discard if cloudy or discolored.

These are general research-handling guidelines. Always follow the specific protocol provided with your research-grade material.

Sources

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. — The New England journal of medicine, 2023. PMID 37366315.
Efficacy and Safety of GLP-1 Medicines for Type 2 Diabetes and Obesity. — Diabetes care, 2024. PMID 38843460.
Emerging pharmacotherapies for obesity: A systematic review. — Pharmacological reviews, 2025. PMID 39952695.
Retatrutide-A Game Changer in Obesity Pharmacotherapy. — Biomolecules, 2025. PMID 40563436.
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 metabolism, 2022. PMID 35985340.
Efficacy and Safety of Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss Among Adults Without Diabetes : A Systematic Review of Randomized Controlled Trials. — Annals of internal medicine, 2025. PMID 39761578.

Retatrutide Guide & Dosage Chart