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GLP-1 / Metabolic

Retatrutide 12mg Guide & Dosage Chart

High-dose retatrutide protocol page (see main retatrutide chart).

Also known asLY3437943
Routesubcutaneous
Retatrutide 12mg — Dosage chart
Every row cited
GoalDoseFrequencyDurationEvidenceSource
Obesity treatment (weight reduction) 12 mg 1x/week 48 weeks Clinical PMID 37366315
Obesity treatment (weight reduction) - dose escalation starting dose 2 mg 1x/week per trial (escalating to 12 mg over 48 weeks) Clinical PMID 37366315
Type 2 diabetes glycemic control and weight loss - dose escalation cohort 3–12 mg 1x/week 12 weeks Clinical PMID 36354040
Type 2 diabetes glycemic control and weight loss - fixed dose 3 mg 1x/week 12 weeks Clinical PMID 36354040
Type 2 diabetes glycemic control and weight loss - dose escalation (3/6 mg) 3–6 mg 1x/week 12 weeks Clinical PMID 36354040
For research and educational use only. Not medical advice.

What is Retatrutide 12mg?

Retatrutide (also called LY3437943) is a synthetic peptide being studied as a treatment for obesity and type 2 diabetes. What makes it stand out is that it targets three hormone receptors at once — GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors — earning it the nickname a "triple agonist."[2] Most well-known weight-loss peptides in this class target one or two receptors; retatrutide hits all three.

This page focuses specifically on the 12 mg dose, the highest dose explored in phase 2 clinical trials.[1] It is a research compound — not approved for human use — and everything here is for educational and research-reference purposes only.

How Retatrutide 12mg Works

Think of retatrutide as a master key that fits three locks instead of one. Each "lock" is a hormone receptor that helps control appetite, blood sugar, and metabolism.

  • GLP-1 receptor: Tells the brain you're full and slows stomach emptying, so you eat less.
  • GIP receptor: Works alongside GLP-1 to further reduce calorie intake.
  • Glucagon receptor: Turns up the body's calorie-burning engine — increasing energy expenditure.

In lab studies, retatrutide showed balanced activity at the glucagon and GLP-1 receptors, with even stronger activity at the GIP receptor.[2] In obese mice, this combination led to weight loss both by cutting calorie intake (via GIP and GLP-1) and by burning more calories (via glucagon).[2] The once-weekly dosing schedule is supported by a half-life of approximately six days.[3]

What the Research Shows

The headline results come from a phase 2 randomized controlled trial published in the New England Journal of Medicine in 2023, involving 338 adults with obesity.[1] Participants receiving 12 mg of retatrutide (starting at 2 mg and escalating) lost an average of 17.5% of body weight by week 24 and 24.2% by week 48, compared to just 2.1% in the placebo group.[1] To put that in perspective: all participants in the 12 mg group achieved at least 5% weight loss by week 48, and 83% lost 15% or more of their body weight.[1] These are among the largest weight reductions ever reported for a pharmacological agent in a trial of this kind.

Earlier phase 1b research in people with type 2 diabetes (12 weeks) showed that the highest escalating dose (reaching up to 12 mg) produced significant reductions in blood sugar — HbA1c dropped by about 1.2 percentage points versus placebo — along with weight loss of nearly 9 kg in the top dose group.[3] The pharmacokinetics confirmed once-weekly dosing is appropriate.[3]

More recently, preclinical research found that retatrutide-induced weight loss was associated with reduced tumor growth in mouse models of pancreatic and lung cancer. Tumor volume was reduced up to 17-fold compared to controls, and some anti-tumor immune effects persisted even after the peptide was withdrawn.[4] Researchers note this is early-stage preclinical work and does not establish benefit in humans.[4]

Retatrutide is also highlighted in broader reviews of incretin-based therapies as a next-generation candidate in the obesity-treatment landscape, alongside approved agents like semaglutide and tirzepatide.[5][6]

What Retatrutide 12mg Is Being Studied For

  • Obesity / weight reduction — the primary focus of phase 2 trials[1]
  • Type 2 diabetes — glycemic control alongside weight loss[3]
  • Metabolic health — improving related markers like blood pressure and lipids[6]
  • Obesity-associated cancer risk — early preclinical exploration[4]

How Retatrutide 12mg Is Dosed in Research

Dosing protocols vary by research objective and subject population. In the key phase 2 obesity trial, researchers used a gradual dose-escalation strategy — starting at 2 mg per week and stepping up to 12 mg over the course of the 48-week study — to help manage gastrointestinal side effects.[1] Type 2 diabetes studies explored both fixed doses and escalating regimens over 12 weeks.[3] All specific dose amounts, schedules, and escalation timings used in published research are laid out in the dosage chart on this page. For weight-based calculations, use the calculator tool.

Mixing and Storing Retatrutide 12mg

Retatrutide 12 mg for research use typically comes as a lyophilized (freeze-dried) powder in a sealed vial. To reconstitute it, researchers use bacteriostatic water (sterile water containing a small amount of benzyl alcohol as a preservative). The water is drawn into a syringe and injected slowly down the inside wall of the vial — not directly onto the powder — then the vial is gently swirled (never shaken vigorously) until the powder fully dissolves to a clear solution. The reconstituted peptide should be stored in a refrigerator (2–8°C / 36–46°F), kept away from light, and used within the timeframe recommended by the supplier — typically within 28–30 days once mixed. Unused lyophilized powder should be stored frozen until needed. These are general research-handling guidelines; always follow the specific instructions provided with your research-grade material.

Sources

  1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. — The New England journal of medicine, 2023. PMID 37366315.
  2. 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.
  3. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. — Lancet (London, England), 2022. PMID 36354040.
  4. Incretin triple agonist retatrutide (LY3437943) alleviates obesity-associated cancer progression. — npj metabolic health and disease, 2025. PMID 40094000.
  5. Incretin-based therapies for the treatment of obesity-related diseases. — npj metabolic health and disease, 2024. PMID 40604322.
  6. Retatrutide in type 2 diabetes mellitus and obesity: an overview. — Expert review of clinical pharmacology, 2026. PMID 41785010.

Retatrutide 12mg FAQ

What is Retatrutide 12mg?
Retatrutide 12mg (LY3437943) is a synthetic peptide and the highest dose studied in phase 2 trials. It is a "triple agonist" that activates GLP-1, GIP, and glucagon receptors simultaneously to reduce body weight and improve blood sugar control.[1][2] It is a research compound — not approved for human therapeutic use.
How does Retatrutide 12mg work?
It activates three hormone receptors at once. GLP-1 and GIP receptor activity reduces appetite and calorie intake, while glucagon receptor activity increases energy expenditure (calorie burning).[2] This triple mechanism is thought to explain why the weight-loss results seen in research appear larger than those from single- or dual-agonist peptides.
What is Retatrutide 12mg used for in research?
Research has focused primarily on obesity treatment and type 2 diabetes management.[1][3] Preclinical work is also exploring potential effects on obesity-associated cancer progression, where retatrutide-treated mice showed dramatically reduced tumor growth compared to controls.[4] All uses are research-only at this stage.
How is Retatrutide 12mg dosed?
In the main phase 2 obesity trial, 12 mg was administered once weekly via subcutaneous injection after a gradual escalation starting at 2 mg — a strategy that helped reduce gastrointestinal side effects.[1] Type 2 diabetes research used shorter 12-week protocols with various fixed and escalating schedules.[3] See the dosage chart on this page for all specific protocols.
How do you reconstitute Retatrutide 12mg?
Research-grade retatrutide powder is typically reconstituted with bacteriostatic water. Add the water slowly down the inner wall of the vial and swirl gently until dissolved. Store the reconstituted solution refrigerated at 2–8°C, away from light, and use within the window specified by your supplier (commonly 28–30 days). Never shake the vial vigorously.
Is Retatrutide 12mg safe?
In phase 2 research, the most common adverse events were gastrointestinal (nausea, vomiting) — dose-related and mostly mild to moderate. A lower starting dose of 2 mg helped reduce these effects.[1] Dose-dependent heart rate increases were observed, peaking at week 24 and declining afterward.[1] Retatrutide is a research compound; safety data in humans beyond clinical trials is not established.