What is Retatrutide?
Retatrutide is a novel, investigational medication developed by Eli Lilly for the treatment of obesity. It is not yet FDA-approved for public use, and any information regarding dosage is derived from clinical trials. Its unique mechanism of action makes it a groundbreaking therapy in the class of incretin mimetics, as it is a triple-agonist, activating three different hormone receptors: GIP, GLP-1, and glucagon.
- GIP (glucose-dependent insulinotropic polypeptide): This incretin hormone enhances insulin secretion in response to glucose.
- GLP-1 (glucagon-like peptide-1): GLP-1 stimulates insulin release, suppresses glucagon secretion, and promotes a feeling of fullness (satiety) by slowing gastric emptying, which helps regulate appetite and blood sugar.
- Glucagon: Unlike other therapies that suppress glucagon, retatrutide activates its receptor, which increases energy expenditure and promotes fat breakdown.
By targeting all three pathways simultaneously, retatrutide appears to offer a more profound effect on weight loss compared to single or dual-agonist therapies.
How much retatrutide per week? A look at clinical trial dosages
Because retatrutide is still in clinical trials, there is no single, officially approved dosage or schedule. The dosage and titration protocols are established and overseen by clinical trial investigators. The goal is always to start with a low dose and gradually increase it, or titrate, to minimize gastrointestinal side effects like nausea and vomiting, which are common with this class of medication.
Based on Phase 2 trials, a typical titration schedule for how much retatrutide per week has been described. This is not a formal recommendation but an example based on research protocols:
Example Retatrutide Titration Approach in Clinical Trials
- Initial Phase: A starting dose is administered once weekly for a period.
- Escalation Phase: The dose is gradually increased at set intervals, such as every four weeks.
- Maintenance Phase: The dose continues to be escalated, potentially to higher weekly levels, depending on individual response and tolerability as determined by the trial protocol.
Higher dosages tested in Phase 2 trials were associated with the most significant weight loss. Some studies have explored various maximum weekly doses. Individual factors like a patient’s initial weight, metabolism, and overall health are all considered by researchers when determining the best dosing pathway within the trial protocols.
Retatrutide vs. Other Incretin-Based Medications
To understand retatrutide's unique place in the market, it is helpful to compare it with other FDA-approved drugs in the same class, such as semaglutide and tirzepatide.
| Medication | Receptor Targets | Clinical Trial Efficacy (Approx. Weight Loss at ~1 Year) | Typical Maintenance Dose (Approved) | FDA Status |
|---|---|---|---|---|
| Retatrutide | GLP-1, GIP, Glucagon | Up to 24.2% (at 48 weeks) | Not yet established (investigational) | Investigational (Phase 3 trials) |
| Tirzepatide | GLP-1, GIP | Up to 20.9% (at 72 weeks) | 10–15 mg weekly | Approved for T2D (Mounjaro) and weight loss (Zepbound) |
| Semaglutide | GLP-1 | Up to 16.0% (at 68 weeks) | 2.4 mg weekly | Approved for T2D (Ozempic) and weight loss (Wegovy) |
Important Safety and Usage Considerations
Investigational Status and Compounded Versions: It is critical to emphasize that retatrutide is not yet available for legal prescription outside of a clinical trial setting. The FDA has warned against purchasing compounded versions of investigational drugs like retatrutide, as they are not tested for safety or efficacy, and their purity and potency are not guaranteed. Attempting to use or calculate doses outside a supervised clinical trial is extremely unsafe.
Common Side Effects: The most common side effects reported in clinical trials are gastrointestinal, including:
- Nausea
- Diarrhea
- Vomiting
- Constipation
These side effects tend to be dose-dependent and typically improve as the body adjusts to the medication, which is why gradual titration within the clinical trial protocols is so important.
Cardiovascular Effects: Some trial participants experienced a temporary increase in resting heart rate, which peaked around week 24 and then declined. Any significant or sustained increase in heart rate should be reported to a healthcare provider immediately.
Medical Supervision: Due to the complex nature of this medication and the need for personalized dosing adjustments, proper medical supervision is essential if it eventually becomes available.
Conclusion
Retatrutide is a highly promising, triple-agonist medication for weight loss that is still undergoing rigorous testing in Phase 3 clinical trials. For individuals participating in these studies, determining how much retatrutide per week involves a carefully controlled, gradual titration schedule to maximize the drug's effectiveness while minimizing side effects. Starting with a low dose and escalating over several weeks allows the body to adjust to the medication's powerful metabolic effects. While early trial results have shown remarkable weight loss potential, it is crucial to remember that retatrutide is not yet approved or available for commercial use. The only safe and legal access is through approved clinical trials, and using unregulated, compounded products is highly discouraged due to significant safety risks. The precise, FDA-approved dosage will only be established after the completion of these trials, potentially paving the way for a new era in obesity treatment.
