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RetatrutideClinical (Phase 2) evidence

Triple-agonist

An investigational GLP-1/GIP/glucagon triple agonist (Lilly) producing the largest weight loss recorded for an anti-obesity drug.

📋 Regulatory status

Investigational — not approved by any regulator. Anything sold as 'retatrutide' outside a clinical trial is unapproved. The phase 3 TRIUMPH programme is ongoing.

Also known as: LY3437943, triple-G agonist

⚙️ How it works

Activates three receptors: GLP-1 and GIP reduce appetite, slow gastric emptying and improve insulin handling, while the added glucagon arm increases resting energy expenditure and hepatic fat mobilisation — lowering intake and raising burn.

🔬 What the research found

The phase 2 obesity trial (NEJM 2023, 338 adults) reported mean weight reduction up to ~24% at 48 weeks at the highest dose versus ~2% on placebo — among the largest losses reported for any pharmacotherapy. A separate phase 2a trial showed reductions in liver fat. Because efficacy data are phase 2 only, long-term safety, cardiovascular outcomes and durability remain unproven pending phase 3. Glucagon-receptor agonism can raise heart rate and affect glucose, which is being watched closely.

We report both positive and negative trial results. For exact study protocols, read the sources — we cite them rather than repackage them.

🎯 What it's studied to help

Bars reflect the strength & volume of research evidence for each use — not a guarantee of results.

Phase 2 showed up to 24% body-weight loss at 48 weeks at the highest dose.
Glucagon-driven energy expenditure plus large liver-fat reductions; long-term data pending.
Incretin arms slow gastric emptying and increase satiety.

⚠️ Side effects reported in studies

Mostly mild-to-moderate, transient gastrointestinal events concentrated during dose escalation, consistent with the incretin class. Dose-dependent heart-rate increases and some cutaneous sensory effects were noted. Long-term human safety is not yet characterised.

🔗 Often researched alongside

Compared with semaglutide and tirzepatide as the next step in incretin agonists. The added glucagon-receptor arm is thought to raise energy expenditure and mobilise liver fat, which is why it is discussed for both obesity and fatty-liver research.

Mechanistic context only — we don't publish combinations, amounts or protocols.

⚖️ How it compares

Versus tirzepatide (dual agonist), retatrutide adds glucagon-receptor agonism and showed numerically greater weight loss in phase 2 — but it is earlier in development and its cardiovascular and long-term profile is not established.

❓ Frequently asked

Is retatrutide approved?

No. It is investigational and only studied in trials. Anything sold outside a trial is unapproved.

Is the ~24% weight loss confirmed?

No. That is a phase 2 figure over 48 weeks. Phase 3 (TRIUMPH) is needed to confirm efficacy, durability and safety.

Why add a glucagon receptor if glucagon raises blood sugar?

At these engineered ratios glucagon agonism is thought to boost energy expenditure and liver-fat clearance while the GLP-1/GIP arms control glucose — but the net balance in humans is still being studied.

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⚠️ Educational research information only — not medical advice. Many peptides are sold strictly for laboratory research and are not approved treatments. The evidence scores reflect research interest and strength, not efficacy or safety for any individual. Always consult a qualified professional.

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