Metabolic Triple hormone receptor agonist (GLP-1/GIP/glucagon)Not FDA-approved · investigational

Retatrutide

Reta · Tri-G · GGG

Evidence: Studied in humans. Example dose: finalize with a provider. Not a fact-check stamp.

0.5 mg – 8-12 mg SubQ Weekly

Incretin-based peptideAnti-obesity investigational drugLong-acting injectable peptide

Retatrutide (LY3437943) is a first-in-class triple agonist peptide targeting GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors simultaneously. Developed by Eli Lilly, it produced the most dramatic weight loss results of any obesity peptide in Phase 2 trials, with participants losing up to 24.2% of body weight at 48 weeks at the highest dose. The triple agonist mechanism addresses appetite suppression (GLP-1), insulin sensitivity and fat metabolism (GIP), and energy expenditure and hepatic fat reduction (glucagon). Retatrutide represents the next generation beyond dual agonists like tirzepatide.

Quick Start

Route

SubQ injection

Start low

0.5 mg SubQ

Frequency

Weekly or twice weekly (compounded versions)

Timing

No strict fasting requirement. Take with or without food.

Starting dose. 0.5 mg — Weekly, stepping up by 0.5 mg no sooner than every 1 to 2 weeks

Any time of day, with or without food. Once weekly.

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Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.

Tiered Protocols · lowest first

Conservative start (titrate by feel)

0.5 mg · SubQ · Weekly

conservative starter

Start here. Step up by 0.5 mg only after 1 to 2 weeks, and only if you felt nothing at all. HOLD at the first dose that quiets appetite; that is your dose, however low it lands. Nausea is a stop sign, not a milestone. On a 30 mg vial with 3 mL BAC water (10 mg/mL) every 0.5 mg step is 5 units.

0.5 mg

Weekly

Standard

Standard escalation

2-4 mg · SubQ · Weekly

human clinical trial · Jastreboff et al. 2023 (N Engl J Med)

The range most commonly run once past the starting phase. Escalate slowly and only while tolerated. Reaching this range is not a goal in itself: if a lower dose is working, staying there is the better outcome.

2-4 mg

Weekly

Advanced

Trial-referenced upper range

8-12 mg · SubQ · Weekly

human clinical trial · Jastreboff et al. 2023 (N Engl J Med)

These are the upper PHASE 2 TRIAL ARMS (1, 4, 8, 9 and 12 mg weekly), shown for reference rather than as a target. The 12 mg arm produced the largest weight loss and also the most GI distress and the largest rise in resting heart rate. Trial participants escalated under supervision over months.

8-12 mg

Weekly

Reconstitution CalculatorU-100

Vial strength

BAC water

Vials in this mix

Syringe size

Target dose

050100u

Draw to

— units

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I will split this dose across more than one syringe

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How it works

Retatrutide activates three receptor systems simultaneously. GLP-1 receptor activation suppresses appetite via hypothalamic signaling, slows gastric emptying, and enhances glucose-dependent insulin secretion. GIP receptor activation improves insulin sensitivity, enhances lipid metabolism in adipose tissue, and may reduce inflammation. Glucagon receptor activation increases hepatic energy expenditure, promotes lipolysis, reduces hepatic fat accumulation, and increases thermogenesis. The glucagon component is what distinguishes retatrutide from tirzepatide (GLP-1/GIP only) and semaglutide (GLP-1 only), and is believed to account for the superior weight loss results through increased energy expenditure.

What to expect

Early

Days 1–7

Weeks 1-4: Appetite suppression noticeable. Nausea common during titration. Initial weight loss primarily from reduced caloric intake. Slow titration minimizes side effects.

Mid

Weeks 2–4

Weeks 4-12: Consistent weight loss. GI side effects typically improve. Body composition changes visible. Blood glucose improvements if metabolically impaired.

Later

Weeks 4–12

Weeks 12-48: Significant cumulative weight loss. Phase 2 showed 17-24% body weight loss depending on dose. Hepatic fat reduction. Metabolic markers improve substantially.

Evidence

HumanPresent

AnimalPresent

In-vitroPresent

Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.

Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.

Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors.

Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial. The New England journal of medicine · 2023 · PMID 37366315

Evidence scope. Phase 2 obesity trial; supports triple-receptor identity, not the card's 0.5 mg escalation or twice-weekly compounded use.

Claims we could not support

No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.

Dose/route: 0.5 mg weekly, stepping up by 0.5 mg no sooner than every 1 to 2 weeks via SubQ injection, Weekly or twice weekly (compounded versions). No checked live PubMed abstract supported this complete molecule/formulation/route/dose/frequency combination.

Primary safety claim: Nausea (most common, dose-dependent). No checked live abstract directly established this as the primary concern for the card's exact formulation and regimen.

The honest take

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Most potent weight loss peptide

Supported

Confirmed by Phase 2 data. 24.2% body weight loss exceeds semaglutide (15-16%) and tirzepatide (20-22%). Triple agonist mechanism provides additive weight loss.

Hepatic fat reduction

Glucagon receptor activation specifically targets hepatic fat. Phase 2 data showed significant liver fat reduction. Promising for NASH/NAFLD.

Energy expenditure increase

Glucagon component increases basal metabolic rate. This distinguishes retatrutide from GLP-1-only agents that primarily reduce intake.

Interactions & stacking

Two different questions: what is documented about running these together, and what is documented about drawing them into the same syringe. A good pharmacological partner can still have to be pinned separately.

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Pin alone. Retatrutide must not share a syringe with anything else, whatever the pharmacology says. PIN ALONE. GLP-1 class. FDA labeling for all GLP-1 agonists specifies separate injections.

Documented together

BPC-157BPC-157 supports GI mucosal healing, may reduce GLP-1 related nausea and gastroparesis. Pin separately.

AOD-9604Retatrutide suppresses appetite, AOD targets fat metabolism directly. Complementary weight management. Pin separately.

Keep separate

SemaglutideDo not stack GLP-1 agonists. Overlapping receptor activation increases nausea, GI distress, and hypoglycemia risk.

TirzepatideDo not stack GLP-1 agonists.

MetforminBoth lower blood glucose. Monitor for hypoglycemia. Dose adjustment may be needed.

InsulinGLP-1 potentiates insulin effects. Hypoglycemia risk. Requires dose adjustment.

Check any specific pair in the Stack & Interaction Checker, which answers both questions separately. Absence of a documented conflict is not evidence of safety.

Side effects & safety

Commonly reported

Nausea (most common, dose-dependent)
Diarrhea
Decreased appetite
Vomiting during titration
Constipation

Less common & notes

Gastroparesis (delayed gastric emptying) with chronic use.
Pancreatitis risk (class effect).
Gallbladder issues with rapid weight loss.
Heart rate increase.
Monitor thyroid (GLP-1 class has thyroid C-cell tumor signal in rodents).
Contraindicated with personal/family history of medullary thyroid carcinoma or MEN2.
Oral contraceptives may be less reliable during dose initiation and escalation: delayed gastric emptying (GLP-1 / amylin) can reduce oral drug absorption - Tirzepatide carries an FDA label warning to use a backup or non-oral method for 4 weeks after starting and after each dose increase.

Pharmacokinetics

Illustrative plasma concentration · 25 d

Half-life

144h

Peak · Tmax

24h

Elimination

720h

Bioavailability

~100%

SubQ

Duration of action

7 days

Supports weekly dosing; appetite suppression sustained between doses

Clearance

Enzymatic degradation and renal elimination (albumin-bound, slow turnover)

Storage. Refrigerate at 2-8C. Protect from light. Stable for 28 days after reconstitution. GLP-1 class peptides are generally stable. Do not freeze after reconstitution.

Regulatory status

Investigational drug (Eli Lilly). Phase 3 trials ongoing. Not yet FDA-approved. Available through compounding pharmacies. WADA status: Not specifically listed but metabolic modulators may fall under S4.

Put it to work

Calculate, log & track

Open Retatrutide straight into OnePin with your vial and dose pre-filled, then let it handle the syringe math and remind you before the vial runs out.

Open Retatrutide in the app →

Go deeper

The guide & community

The complete Retatrutide walkthrough, real protocol discussion and coaching live inside the BlessUp community on Skool.

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