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GLP-1RetatrutideInvestigational

Retatrutide: the GLP-3 triple agonist

Retatrutide activates GLP-1, GIP, and glucagon receptors simultaneously. Here is what the published phase 2 trial actually showed, how dosing compares to semaglutide and tirzepatide, and the regulatory state in 2026.

Peptide Calculator Log Editorial5 min read
Important

Retatrutide is not FDA-approved for any indication as of April 2026. The information below summarizes published clinical-trial data — it is not a clinical recommendation, and it is not a guide for self-administration. If you are considering using a research compound, talk to a licensed healthcare provider first.

Retatrutide is the most-searched investigational peptide of the past twelve months — search interest is up roughly 4× year-over-year. Most of that traffic is from people trying to figure out one specific thing: how it differs from semaglutide and tirzepatide, and whether the math is meaningfully different.

Short answer to the second part: yes, it's different — both the mechanism and the typical investigational dose range. Here's what the published research actually says.

What retatrutide is

Retatrutide is a synthetic peptide that activates three receptors at once:

  • GLP-1 (the same target as semaglutide / Ozempic®, Wegovy®)
  • GIP (the second target tirzepatide hits — Mounjaro®, Zepbound®)
  • Glucagon (the third target, unique to retatrutide among major weight-management investigational peptides)

The shorthand "GLP-3" floating around online refers to this triple mechanism. It is not an officially designated drug class — it's a search-friendly nickname that has caught on. The technically accurate description is GLP-1 / GIP / glucagon receptor triple agonist.

The hypothesis behind triple agonism: hitting glucagon adds a thermogenic component on top of the appetite-suppression and gastric-emptying effects of GLP-1 and GIP. Whether that translates into a meaningfully different clinical profile is what the trials are designed to test.

How it compares to semaglutide and tirzepatide

CompoundReceptorsStatus (US, Apr 2026)Brand names
SemaglutideGLP-1FDA-approvedOzempic®, Wegovy®, Rybelsus®
TirzepatideGLP-1 + GIPFDA-approvedMounjaro®, Zepbound®
RetatrutideGLP-1 + GIP + glucagonPhase 3 (investigational)None — research only

The receptor count is the easy part to keep straight. The harder part is the dose math: each compound has its own typical mg range, vial size, and titration schedule.

Typical investigational dose range

The phase 2 trial published in the New England Journal of Medicine (Jastreboff et al., 2023) tested four dose arms in adults with obesity: 1 mg, 4 mg, 8 mg, and 12 mg, dosed weekly via subcutaneous injection, with a fixed initial titration ramp.

PhaseWeeksDose
Ramp 1starting dose in most reported protocols1–42 mg / week
Ramp 25–84 mg / week
Ramp 39–128 mg / week
Maintenancehighest dose tested in the published trial13+12 mg / week

This is the "Retatrutide — Escalating" template the iOS app loads by default. Lower-dose protocols (capping at 4 or 8 mg) appear in some follow-on studies. Verify with your provider which schedule is appropriate; the right ramp depends on individual tolerability and the specific trial design being followed.

If you want to see the units math against your specific vial size, the free reconstitution calculator preselects retatrutide:

Inputs

Peptide preset
Syringe

Retatrutide common vial sizes: 10 mg, 20 mg. Typical dose range: 112 mg. Research publications. Not medical advice.

Draw on U-100
10.0units

for a 1 mg dose

Concentration
10.0 mg/ml
Volume
0.100 ml
Per ml
100 u

Not medical advice. Always verify against your vial label and your provider's instructions. Re-check before drawing.

Side effects observed in the published trial

The phase 2 trial reported a side-effect pattern broadly similar to other incretin-class agents — gastrointestinal symptoms dominated:

  • Nausea (most common, dose-dependent, usually worst in the first weeks after a dose increase)
  • Diarrhea
  • Vomiting
  • Constipation
  • Decreased appetite (the intended effect, but worth tracking against protein intake)

A small percentage of participants in the highest-dose arms discontinued due to side effects. As with semaglutide and tirzepatide, the label-style guidance from the trial protocol involves slow titration to manage GI adaptation.

Important

The trial results above are from a population of adults under medical supervision in a controlled study. They are not a prediction of individual results, and they do not characterize long-term safety.

Where it stands clinically in 2026

Retatrutide is in phase 3 trials for obesity, type-2 diabetes, and related metabolic indications. Eli Lilly publishes program updates; ClinicalTrials.gov has the active trial list. There is no FDA approval and no expected near-term timeline — phase 3 typically runs 2–4 years before submission, and the final result depends on the trial outcomes.

This means retatrutide is not legally available as an approved medication in the US. Any use is research-only, must come through a licensed provider, and falls outside what this site (or any consumer information source) can offer dosing advice on.

Tracking it if you're in a trial or research setting

If you are using retatrutide under provider supervision and need a clean way to track the protocol, the iOS app handles:

  • The 4-phase weekly ramp (auto-advancing through week 1, week 5, week 9, week 13)
  • Reconstitution math against whatever vial size you're working with
  • Injection-site rotation across abdomen / thigh / upper arm
  • Side-effect timeline tracking against the dose-escalation curve
  • A doctor-ready PDF export for your trial coordinator or provider

Get the app — free to install, free for basic tracking.

Bottom line

Retatrutide is the most actively-researched investigational weight- management peptide right now. The math differs from semaglutide (mg-per-week is roughly 5× higher; you draw more units per dose) and from tirzepatide (also higher mg, but with a different titration shape). Until phase 3 finishes, it remains a research compound — interesting to follow, not something to self-administer.

For the actual values to plug into a calculator, see the retatrutide reference page.

References

Track this protocol on autopilot

The iOS app advances ramps week by week, fires reminders, and exports a doctor-ready PDF.

Download on theApp Store