Retatrutide

Trial Not FDA-approved

DeveloperEli Lilly

Key paperJastreboff et al., NEJM 2023 (Phase 2 obesity)

Route in trialsOnce-weekly SC

Half-life contextOn the order of ~6 days

What it is

Retatrutide is an investigational peptide agonist at three receptors: GLP-1, GIP, and glucagon. It is further along than typical “research peptides,” but it is not an approved medicine. Research-chemical vials sold under this name are not trial drug.

Benefits in plain language

What researchers and reference users usually mean when they talk about this compound. These are study themes and common claims — not a promise that it will do this in you.

A triple gut-hormone mimic (GLP-1 + GIP + glucagon) studied for large weight-loss numbers in trials.
In plain terms: it turns down appetite, slows the stomach, and tweaks how the body burns and stores fuel.
Trial patients also saw metabolic lab shifts (glucose, lipids) along with the scale.
Not an approved consumer peptide vial. Trial drugs and research powders are not the same product.

If a branded, FDA-approved product exists, that label is the only dose that is actually authorized. Research-chemical vials are a different object.

Mechanism of action

GLP-1 and GIP activity reduce appetite and improve incretin-mediated insulin secretion; glucagon-receptor activity adds energy-expenditure and hepatic-fat effects in the trial narrative. Combined, Phase 2 showed large mean weight reductions at 48 weeks, with a clear dose relationship.

Possible side effects

Dominant: gastrointestinal (nausea, vomiting, diarrhea, constipation), worse during uptitration and at higher weekly doses. Trials also noted dose-related heart-rate increase that peaked then receded, and dysesthesia in some arms. Starting at 4 mg instead of 2 mg worsened GI events. Gallbladder and lean-mass questions that apply to the incretin class still apply.

Protocol ranges (Phase 2 obesity trial logic)

Source tier	Amount	Cadence	Notes
Trial	Start 2 mg weekly	Hold ~4 weeks	Lower start improved GI tolerability vs 4 mg start
Trial	4 mg → 8 mg → 12 mg	Escalate about every 4 weeks	Arms targeted 4, 8, or 12 mg maintenance
Trial	1 mg weekly	Fixed	Lower-efficacy exploratory arm

48-week mean weight change in NEJM Phase 2 reached the high teens to ~24% at the top dose versus ~2% placebo. That is trial drug under monitoring — not a gray-market protocol.