Retatrutide

Triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously. The glucagon receptor activation adds a thermogenic and lipolytic dimension absent from dual agonists — glucagon drives hepatic glycogenolysis, increases energy expenditure, and mobilizes adipose stores. The three-receptor approach creates a metabolic cascade that addresses insulin sensitivity, appetite, and energy expenditure through independent but synergistic pathways.

Half-life

~5 days (~120 hours, estimated from phase 2 PK data)

Bioavailability

~80% (SC, estimated)

Route

subcutaneous

Evidence tier

T3 — Community / emerging

Optimization pillars

fat-loss · cellular-health

References

2 peer-reviewed

Dose ranges

Three tiers ordered by aggressiveness. Tier chips on every OPTIMIZE intervention let you filter the catalog by your evidence tolerance.

conservative

0.5–2 mg/week SC

Phase 2 low-dose cohort

moderate

4–8 mg/week SC

Phase 2 mid-dose cohort

aggressive

8–12 mg/week SC

Phase 2 high-dose cohort (maximum studied)

Monitoring

fasting-glucose
hba1c
fasting-insulin
homa-ir
lipid-panel
thyroid-panel
alt
ast
hs-crp
creatinine
egfr

Contraindications

medullary-thyroid-carcinoma
men2-syndrome
pancreatitis-history
severe-gastroparesis
hepatic-impairment-severe

References

PMID:37351564Retatrutide, a GIP, GLP-1 and Glucagon Receptor Agonist, for People with Type 2 Diabetes — Lancet, 2023
PMID:37351563Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial — N Engl J Med, 2023

Notes

Retatrutide is the next logical step in incretin pharmacology and the data from phase 2 makes the trajectory clear. 24.2% mean body weight reduction at the highest dose over 48 weeks. That exceeds tirzepatide. The glucagon receptor adds something the dual agonists cannot replicate — direct thermogenic drive. Your body burns more energy at rest. The concern, reasonably, is hepatic glucose output. Glucagon tells your liver to dump glycogen. In a diabetic patient, that is counterproductive. But the GLP-1 and GIP components counterbalance hepatic glucose spikes through insulin secretion. Three forces in tension producing a result none could achieve alone. Phase 3 trials will determine whether the safety profile holds at scale.

This is not medical advice

Discuss with a licensed clinician before starting, stopping, or changing any compound. This page documents what the research literature describes — it is not a prescription.

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