Retatrutide

Overview

What it is, in plain language

Retatrutide (LY3437943) is Eli Lilly's investigational triple-receptor agonist, currently in Phase 3 trials (the TRIUMPH program) for obesity and type 2 diabetes. It activates three metabolic receptors simultaneously — GLP-1, GIP, and glucagon — and is the most potent compound in the incretin class to date.

It sits at the cutting edge of metabolic research and is positioned in the AEON line as the apex metabolic study compound. Retatrutide has not been approved by the TGA or any other regulatory body. AEON supplies it for in-vitro research only — not for human therapeutic use.

Three receptors, simultaneously — GLP-1, GIP, and glucagon. What distinguishes Retatrutide from semaglutide (GLP-1 only) and tirzepatide (GLP-1 + GIP) is the third arm.

Mechanism

How it works

Retatrutide engages GLP-1 receptors (appetite and insulin), GIP receptors (insulin and adipose handling), and glucagon receptors (energy expenditure and hepatic-fat mobilisation). The simultaneous engagement is what distinguishes it from semaglutide (GLP-1 only) and tirzepatide (GLP-1 + GIP).

Research findings

What the literature shows

Phase 2 trial readouts reported approximately 24% body-weight reduction at 48 weeks at the 12 mg weekly dose — the highest sustained reduction reported in the incretin class.

Improvements in glycaemic control and liver-fat markers have exceeded earlier-generation benchmarks in head-to-head readouts.

Phase 3 trials are ongoing as of 2026; regulatory approval has not been granted in any jurisdiction. All AEON Retatrutide is for in-vitro research only.

Cycle & Handling

Protocol reference

Common research-grade reference figures. Not medical advice — every protocol must be reviewed against the latest published literature and your study design.

Cycle guidance

Retatrutide is not cycled like the regenerative peptides. It functions as a continuous metabolic compound. The structure is: titration phase (12–20 weeks), active phase (6–18 months at the tolerated maximum), then a maintenance step-down (2.0–4.0 mg/week). Hard discontinuation is consistently associated with rebound and weight regain across the GLP-1 class. Pauses, if required, are tapered, not stopped. GI side-effects (nausea, fatigue, appetite suppression) are dose-dependent and slow titration is consistently described in the literature as essential.

Reconstitution

10 mg vial: 2 mL BAC → 5 mg/mL. Draw 0.4 mL = 2 mg; 0.8 mL = 4 mg. 20 mg vial: 2 mL BAC → 10 mg/mL. Draw 0.2 mL = 2 mg; 0.4 mL = 4 mg; 0.8 mL = 8 mg. 40 mg vial: 3 mL BAC → 13.3 mg/mL. Draw 0.15 mL = 2 mg; 0.30 mL = 4 mg; 0.60 mL = 8 mg; 0.90 mL = 12 mg.

Storage

Lyophilised vial: room temperature short-term, refrigerator long-term. Reconstituted: refrigerate; use within 28 days when reconstituted with bacteriostatic water.

FAQ