GLP-1 & Metabolic Peptides
Retatrutide (LY3437943)
Commonly used for
Weight LossMetabolic HealthHeart Health
What is it?
Retatrutide is a novel triple agonist targeting the GLP-1, GIP, and glucagon receptors, producing substantial weight loss through appetite suppression and increased energy expenditure.
Mechanism of action: GLP-1 receptor agonist (appetite suppression, improved glycemic control); GIP receptor agonist (enhances insulin secretion and may improve adipose metabolism); Glucagon receptor agonist (increases energy expenditure and fat oxidation); This triple mechanism aims to combine reduced caloric intake with increased energy expenditure.
What do people use it for?
Proposed indications: Obesity; Type 2 Diabetes; MASH (Metabolic Dysfunction–Associated Steatohepatitis); Cardiovascular Risk Reduction; Obstructive Sleep Apnea (secondary to weight loss)
How is it used? / Dosing
Reported dosing range*: 1, 4, 8, or 12 mg once weekly, subcutaneous
The Phase 2 obesity trial evaluated once-weekly subcutaneous doses of 1 mg, 4 mg, 8 mg, and 12 mg, with some arms starting at a 2 mg dose and escalating over the first several weeks (Jastreboff AM et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine).
*General range reported in available research or other sources -- not an individualized recommendation. Actual use should be supervised by a qualified provider.
Typical clinical dosing schedule: Gradual weekly dose escalation has been used in clinical trials. No approved dosing regimen exists.
Administration: Subcutaneous injection — Weekly (clinical trials)
How does it compare?
Compare with:
How well does it work? / Evidence
~ Moderate evidence
Evidence rating: ⭐⭐⭐⭐☆ — Large Phase 2 trial demonstrated up to ≈24.2% weight loss at the 12-mg dose at 48 weeks.
Landmark trials: Phase 2 Obesity Trial (2023) — Up to ≈24.2% weight loss at the 12-mg dose at 48 weeks — largest weight loss reported for any obesity medication to date in a Phase 2 trial.
Safety & side effects
Common side effects: Nausea, Vomiting, Diarrhea, Constipation, Reduced appetite
Serious risks: Potential class-related concerns: Pancreatitis; Gallbladder disease; GI intolerance; Dehydration; Long-term cardiovascular safety remains under investigation.
Drug interactions: Potential delayed gastric emptying may alter absorption of oral medications.
Monitoring: Weight, HbA1c, Blood pressure, Renal function, GI tolerance
Legal & regulatory status
Legal status: Investigational. Not FDA-approved and not available by prescription — currently accessible only through enrollment in a clinical trial.
Regulatory status: Phase 3 Clinical Trials • Not FDA Approved
Who should avoid it?
Contraindications: No approved labeling exists. Clinical trials generally excluded:; Personal/family history of medullary thyroid carcinoma; MEN2 syndrome; Pregnancy; Severe GI disease
Pregnancy & breastfeeding: Avoid.
Research & references
Jastreboff AM, et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity. New England Journal of Medicine, 389, 514–526. https://doi.org/10.1056/NEJMoa2301972