Retatrutide

Retatrutide (LY3437943) is an investigational 39-residue lipidated peptide from Eli Lilly. It is a single molecule that activates three receptors simultaneously — GIP, GLP-1, and glucagon — unlike tirzepatide's dual GIP/GLP-1 profile.

Cellaire classifies Retatrutide as clinical (phase 2) evidence for an unapproved investigational drug. Published trials report a ~6-day half-life supporting once-weekly dosing, 22.8% and 24.2% body-weight reduction at 48 weeks with 8 mg and 12 mg doses, and relative liver-fat reductions of 81.4–82.4% at week 24 (Sanyal et al. analysis, PMC11271400). There is no legal compounding pathway — retatrutide remains investigational.

Retatrutide is a 39-residue peptide with Aib substitutions at positions 2 and 20, α-methyl-leucine at position 13, a C20 fatty-diacid tethered via AEEA-γGlu on Lys17, and a C-terminal serinamide.

The C20 acyl side chain drives albumin binding, giving the ~6-day plasma half-life. Once-weekly subcutaneous dosing is used in phase-2 trials.

It agonizes GIP, GLP-1, and glucagon receptors. Phase-2 obesity and MASH trials report the largest weight and liver-fat reductions published for any once-weekly incretin to date, though the pivotal phase-3 program is ongoing.

Retatrutide is not FDA-approved for any indication. As an investigational drug still under exclusivity, there is no legal compounding pathway; unregulated retatrutide sold outside a clinical trial is not the same molecule that Lilly manufactures for its trials.