With Pramlintide
Safety flag
Additive gastric-emptying delay, GI intolerance, and glucose lowering are plausible; a broad clinical contraindication is not established.
Interaction evidence source All research profiles
GLP-1 / GIP / glucagon
Retatrutide
Prepared by the ezGLP team. Sources last checked . Profile reviewed .
Routes represented in the knowledgebase: Subcutaneous (SubQ).
Educational overview
Retatrutide is listed in the ezGLP knowledgebase under GLP-1 / GIP / glucagon. Evidence and regulatory status can vary by formulation, route, and jurisdiction.
Retatrutide (LY3437943) is an investigational once-weekly injectable peptide developed by Eli Lilly that activates three receptors at once: the glucagon-like peptide-1 (GLP-1) receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon receptor. It is usually described as a triple agonist and belongs to the same incretin-based family as semaglutide and tirzepatide. GLP-1 and GIP signalling reduce appetite and improve insulin secretion, while glucagon receptor activity is thought to add energy expenditure and liver-fat effects. The molecule is a fatty-acid-acylated peptide engineered for a long circulating half-life, which Lilly's discovery paper reported at roughly six days in humans, supporting weekly administration.
Evidence comes mainly from two Lilly-sponsored phase 2 randomised trials published in 2023. The obesity trial (Jastreboff et al., NEJM) enrolled 338 adults without diabetes for 48 weeks and reported mean weight reductions of up to about 24 percent at the highest dose compared with about 2 percent on placebo. The type 2 diabetes trial (Rosenstock et al., Lancet) enrolled 281 adults for 36 weeks and reported HbA1c reductions and weight loss exceeding those seen with dulaglutide. Gastrointestinal events such as nausea, diarrhoea, vomiting and constipation were the most common adverse effects and dose related. Phase 3 trials (the TRIUMPH programme) were still running at this review, so long-term safety, cardiovascular outcomes and rare adverse events remain unestablished.
Retatrutide is not approved by the FDA, the EMA or any other regulator for any indication, and no commercial formulation exists. The only legitimate human exposure is within registered clinical trials, where the sponsor supplies it as a subcutaneous injection. The FDA states on its page about unapproved GLP-1 products that retatrutide cannot be used in compounding under federal law and is not a component of any approved drug. The agency has issued warning letters to telehealth companies, active-ingredient distributors and outsourcing facilities that marketed or repackaged retatrutide, and to companies selling vials labelled 'for research purposes' or 'not for human consumption' that were in practice sold for human use with dosing instructions.
Because there is no approved product label, no authoritative storage or in-use guidance exists for retatrutide outside a trial protocol. Material sold online is typically a lyophilised powder of unverified identity, purity and sterility, and the FDA has flagged dosing errors and multi-dose-vial contamination risks with compounded incretin products generally. A dose log or inventory record kept for a research compound has no label to reconcile against, so entries that capture the supplier, lot or batch identifier, reconstitution date, resulting concentration and storage temperature are the only way to trace what was actually administered. Records without those fields cannot be reconciled later if a product-quality question arises.
- Category
- GLP-1 / GIP / glucagon
- Routes represented
- Subcutaneous (SubQ)
- Approximate library half-life
- 144 hours; formulation-dependent and not dosing guidance
- Storage context
- Follow the dispensed product label; storage and in-use limits vary by brand and formulation.
Published literature
Safety evidence
Common or reported: nausea, diarrhea, vomiting, constipation.
Investigational; long-term and rare adverse effects are not established.
Safety evidence sourceInteraction evidence
These are general, pairwise evidence notes. Green identifies the potential-synergy category, while Lv3/Lv2/Lv1 communicates evidence strength; it does not guarantee benefit or cancel a safety warning.
Common questions
Is retatrutide FDA approved?
No. Retatrutide is an investigational compound that has not been approved by the FDA, the EMA or any other regulator for any use. It is being studied in Eli Lilly's phase 3 TRIUMPH programme after phase 2 trials published in 2023. The FDA states that retatrutide cannot be used in compounding under federal law and has warned companies that sold it directly to consumers, including vials labelled as research chemicals.
How much weight did people lose on retatrutide in trials?
In the 48-week phase 2 obesity trial published in the New England Journal of Medicine in 2023, adults without diabetes lost on average up to about 24 percent of body weight at the highest dose, against about 2 percent on placebo, and weight loss had not plateaued when the study ended. In the type 2 diabetes phase 2 trial, weight reductions were smaller but still exceeded those with dulaglutide. These figures are group means from trials, not expected individual outcomes.
What is the difference between retatrutide and tirzepatide?
Tirzepatide activates two receptors, GLP-1 and GIP, and is an approved medicine in many countries. Retatrutide adds a third target, the glucagon receptor, which is thought to raise energy expenditure and reduce liver fat, and it remains investigational. Both are once-weekly acylated peptides from Eli Lilly with multi-day half-lives. No head-to-head trial has been published, so comparisons rest on separate studies with different populations and durations.
What are the side effects of retatrutide?
In phase 2 trials the most common adverse events were gastrointestinal: nausea, diarrhoea, vomiting and constipation, mostly mild to moderate and more frequent at higher doses and during dose escalation. Investigators also reported increases in heart rate and some cases of skin sensitivity changes (dysesthesia). Because only a few hundred people have been followed for less than a year in published studies, uncommon and long-term effects are not yet characterised.
Can retatrutide be legally compounded or bought online?
According to the FDA, retatrutide is not a component of any approved drug and cannot lawfully be used in compounding in the United States. Products sold online as 'research chemicals' are unapproved drugs when marketed for human use, and the agency has issued warning letters to sellers, distributors and telehealth companies. Outside registered clinical trials there is no regulated source, and identity, purity and sterility of such products are unverified.
Further reading
- Jastreboff et al., N Engl J Med 2023 (phase 2 obesity trial)
- Rosenstock et al., Lancet 2023 (phase 2 type 2 diabetes trial)
- Coskun et al., Cell Metab 2022 (discovery and clinical proof of concept)
- ClinicalTrials.gov NCT04881760 (phase 2 obesity study record)
- FDA, Concerns with unapproved GLP-1 drugs used for weight loss
- Hamza et al., Curr Cardiovasc Risk Rep 2025 (triple agonism review)
Summarised from published literature for reference only, with citations to the source. Evidence is graded as reported and is not a recommendation to combine, dose, or use any compound.
For personal tracking and education only. Not medical advice, diagnosis, or treatment, and not a medical device. Peptides may be prescription-only or unapproved where you live. Consult a licensed healthcare professional.