Investigational·Triple agonist (GLP-1 + GIP + Glucagon receptors)

Retatrutide

aka LY3437943

Education only. Many compounds discussed are research chemicals not approved for human use in the US. This is not medical advice — consult a licensed physician.

What it is

A novel triple receptor agonist activating GLP-1, GIP, and glucagon receptors simultaneously. The added glucagon receptor activity drives hepatic fat oxidation in addition to the appetite-suppression seen with GLP-1 mono-agonists.

How it works

GLP-1 receptor activation suppresses appetite and slows gastric emptying. GIP receptor activation enhances insulin secretion. Glucagon receptor activation increases energy expenditure and lipolysis in the liver.

What the research says

Phase 2 trial (NEJM 2023) showed up to 24.2% body weight loss at 48 weeks at 12mg weekly — the largest weight reduction reported for any GLP-class compound. Phase 3 trials ongoing.

Sources: NEJM 2023 Phase 2 · ClinicalTrials.gov NCT05882045

Common dosing ranges

Range: Phase 2 trials tested 1, 4, 8, 12 mg weekly. Microdose protocols start at 0.25–0.5 mg.
Frequency: Once weekly (half-life ~6 days)
Duration: Trial protocols ran 48 weeks

Sources: NEJM 2023

Administration

SubQ

Half-life

~6 days

Side effects

Common

Nausea
Diarrhea
Vomiting
Constipation
Decreased appetite

Serious / theoretical

Possible thyroid C-cell tumors (per GLP-1 class warning)
Pancreatitis (rare)

Sources: NEJM 2023 safety data

Notes

Not FDA-approved. Eli Lilly is the developer. Often acquired from compounding pharmacies or research-grade suppliers in the US.