whatpeptidestostack
← Compound library
Retatrutide
A single peptide that activates the GIP, GLP-1 and glucagon receptors. It has the strongest human evidence in this atlas and, as of this update, no approved use.
The basics
| Human protocol on record | 21 figures |
|---|---|
| Animal or laboratory figures | 0 |
| Published records retrieved | 29 |
| Registered trials | 20 |
| Certificate of analysis | Published by the partner |
| Regulatory status | Research-grade material, no approved human use |
1. The protocol on record
Hard disclaimer. Figures below are transcribed from a published study or an approved label exactly as the source states them. They record what researchers administered in a trial population, not instructions for any person, and none of it is adjusted to you. Most compounds here have no approved human use. Do not act on any of it without a licensed prescriber who knows your history.
Amounts and schedules, human record
| Phase or model | Amount | Frequency | Timing | Route | Duration | Source |
|---|---|---|---|---|---|---|
| Phase 2 obesity trial, 1 mg arm | 1 mg | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 obesity trial, 4 mg arm, initial dose 2 mg | 4 mg (initial dose, 2 mg) | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 obesity trial, 4 mg arm, initial dose 4 mg | 4 mg (initial dose, 4 mg) | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 obesity trial, 8 mg arm, initial dose 2 mg | 8 mg (initial dose, 2 mg) | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 obesity trial, 8 mg arm, initial dose 4 mg | 8 mg (initial dose, 4 mg) | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 obesity trial, 12 mg arm, initial dose 2 mg | 12 mg (initial dose, 2 mg) | once weekly | not stated | subcutaneous | 48 weeks | source |
| Phase 2 type 2 diabetes trial, lowest maintenance arm | 0.5 mg maintenance | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 2 type 2 diabetes trial, 4 mg escalation arm | 4 mg maintenance (starting dose 2 mg) | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 2 type 2 diabetes trial, 4 mg fixed arm | 4 mg maintenance (no escalation) | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 2 type 2 diabetes trial, 8 mg arm, starting dose 2 mg | 8 mg maintenance (starting dose 2 mg) | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 2 type 2 diabetes trial, 8 mg arm, starting dose 4 mg | 8 mg maintenance (starting dose 4 mg) | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 2 type 2 diabetes trial, 12 mg arm, starting dose 2 mg | 12 mg maintenance (starting dose 2 mg) | once weekly | not stated | injection | 24-week primary endpoint, secondary endpoints at 36 weeks | source |
| Phase 1b type 2 diabetes trial, lowest ascending-dose cohort | 0.5 mg | once weekly | not stated | subcutaneous | 12 weeks | source |
| Phase 1b type 2 diabetes trial, second cohort | 1.5 mg | once weekly | not stated | subcutaneous | 12 weeks | source |
| Phase 1b type 2 diabetes trial, 3 mg cohort | 3 mg | once weekly | not stated | subcutaneous | 12 weeks | source |
| Phase 1b type 2 diabetes trial, stepwise escalation cohort | 3/6 mg | once weekly | not stated | subcutaneous | 12 weeks | source |
| Phase 1b type 2 diabetes trial, highest stepwise escalation cohort | 3/6/9/12 mg | once weekly | not stated | subcutaneous | 12 weeks | source |
| Systematic review restating the phase 2 obesity trial | 12 mg | once weekly | not stated | not stated | 48 weeks | source |
| Network meta-analysis of obesity trials | 12 mg or 8 mg | not stated | not stated | not stated | included trials ran at least 16 weeks | source |
| Review article, dose range restated | 1 mg to 12 mg | not stated | not stated | not stated | 24-week primary endpoint | source |
| Meta-analysis restating the top trial dose | 12 mg | not stated | not stated | not stated | not stated | source |
Half-life and why the schedule looks like that
The phase 1b multiple-ascending dose trial in people with type 2 diabetes states: "The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days" (PMID:36354040). The discovery-to-clinical-proof-of-concept paper states that the pharmacokinetic profile of LY3437943 "supported once-weekly dosing, and a reduction in body weight persisted up to day 43 after a single dose" (PMID:35985340). A commentary on the phase 1b trial likewise states that "pharmacokinetics support once-weekly dosing" (PMID:37086147). Consistent with that half-life, every interventional human trial in the record dosed retatrutide once weekly: the phase 2 obesity trial dosed once weekly f
Handling and storage
- Lyophilised storage: Not stated in the cited record. - Storage after reconstitution: Not stated in the cited record. - Temperature: Not stated in the cited record. - Light: Not stated in the cited record. - Stability duration: Not stated in the cited record. No cited source and no approved label in the record states reconstitution, storage temperature, or stability for retatrutide. No approved label exists in the record, so there is no label storage text to quote.
These figures summarise what published research and approved labels describe. They are educational, not a recommendation or a personal protocol. Any dose, schedule, or decision to use a compound belongs with a licensed prescriber.
Open the interactive builder for reconstitution maths and a calendar →
2. Safety and harm reduction
Reported adverse effects
| Effect | How often reported | Population | Source |
|---|---|---|---|
| Gastrointestinal adverse events | "most common" among adverse events; dose-related; mostly mild to moderate; partially mitigated with a lower starting dose (2 mg vs. 4 mg) | Phase 2 trial, 338 adults with obesity | PMID:37366315 |
| Dose-dependent increase in heart rate, peaking at 24 weeks and declining thereafter | frequency not stated | Phase 2 trial, 338 adults with obesity | PMID:37366315 |
| Nausea, diarrhea, vomiting | "most frequent" adverse events | Phase 2 trial, adults with obesity (commentary restating it) | PMID:37947489 |
| Heart rate increase | up to 6.7 beats/min | Phase 2 trial, adults with obesity (commentary restating it) | PMID:37947489 |
| Treatment-emergent adverse events, gastrointestinal disorders most frequent | 33 of 52 (63%) on LY3437943, 8 of 15 (54%) on placebo | Phase 1b trial, adults with type 2 diabetes | PMID:36354040 |
| Gastrointestinal adverse events, most commonly nausea, vomiting, diarrhea, constipation | 47% to 84% on a GLP-1 agent vs. 13% to 63% on placebo (class-wide range across agents, including retatrutide) | Systematic review of 26 RCTs, adults with overweight or obesity without diabetes | PMID:39761578 |
| Adverse events requiring treatment discontinuation | 0% to 26% on a GLP-1 agent vs. 0% to 9% on placebo (class-wide range) | Systematic review of 26 RCTs, adults with overweight or obesity without diabetes | PMID:39761578 |
| Serious adverse events | 0% to 10% on a GLP-1 agent vs. 0% to 12% on placebo; described by the source as "rare" (class-wide range) | Systematic review of 26 RCTs, adults with overweight or obesity without diabetes | PMID:39761578 |
| Mild-to-moderate gastrointestinal adverse events, mainly nausea, vomiting, constipation, and diarrhea | "increased frequency" at the highest retatrutide doses; attributed by the source to rapid dose escalation and higher starting dose | Overview of trials in type 2 diabetes and obesity | PMID:41785010 |
| Adverse events (overall) | higher incidence in patients without type 2 diabetes than in those with type 2 diabetes; no intervention increased serious adverse events or hypoglycemic events | Network meta-analysis of 27 RCTs in obesity or overweight | PMID:39305981 |
| Adverse events (comparative risk) | "Retatrutide had the highest AE risk" among the agents compared | Bayesian network meta-analysis of 19 RCTs, adults with BMI 25 or higher | PMID:40685589 |
| Loss of lean mass | about 10% or about 6 kg, stated for incretin-based agents including retatrutide | Narrative review of incretin therapy trials, adults with overweight and obesity | PMID:38687506 |
Cautions stated in the literature
- Heart rate increased by up to 6.7 beats/min on retatrutide, which the source states "may be detrimental and offset some of the benefits of weight loss" (PMID:37947489).
- Gastrointestinal side events were dose-related and were partially mitigated with a lower starting dose (2 mg vs. 4 mg) (PMID:37366315).
- Mild-to-moderate gastrointestinal adverse events were more frequent at the highest doses, likely due to rapid dose escalation and higher starting dose (PMID:41785010).
- Incretin-based agents including retatrutide caused rapid and significant loss of lean mass (about 10% or about 6 kg), which the source links to sarcopenia and frailty risk (PMID:38687506).
- Retatrutide carried the highest adverse-event risk among the compared agents in one network meta-analysis (PMID:40685589).
- A review of GLP-1 medicines, the class retatrutide belongs to, discusses as safety domains: gastrointestinal motility, retained gastric contents and anesthesia, pancreatic and biliary tract disorders, muscle strength, bone density and fractures, and the risk of cancer (PMID:38843460).
- Long-term safety is not established: "The safety of retatrutide needs to be determined in larger and longer trials" (PMID:37086147). Phase 3 trials were still recruiting or active in the record, with no results posted (PMID:41090431; NCT07232719; NCT06260722; NCT06662383; NCT07035093).
Stop and get help
- A severe or worsening reaction of any kind: stop and contact a licensed clinician.
- Signs of an allergic reaction, such as rash, swelling of the face or throat, or difficulty breathing: stop and seek emergency care.
- Signs of injection-site infection, such as spreading redness, warmth, swelling, pus, or fever: stop and contact a licensed clinician.
- Any effect that is unexpected and persistent, including persistent gastrointestinal symptoms that do not resolve: stop and contact a licensed clinician.
- A noticeable or sustained change in heart rate: stop and contact a licensed clinician.
Retatrutide at Peptara Labs
Open the Retatrutide pageRead the third-party certificate of analysis before anything else. Research-grade material, research use only.