Retatrutide
Also known as: LY3437943 · Reta
Contents
MW
4603.42 Da
Amino Acids
39 AA
Half-Life
6 days
Route
SubQ
CAS
2381089-83-2
Mechanism of Action
Retatrutide is the first triple incretin receptor agonist, simultaneously activating GLP-1R, GIPR (glucose-dependent insulinotropic polypeptide receptor), and GcgR (glucagon receptor).
GLP-1R: Appetite suppression, glucose-dependent insulin secretion, gastric emptying delay — same as semaglutide.
GIPR: Potentiates insulin secretion, promotes adipose tissue remodeling and lipid handling — same addition as tirzepatide.
GcgR (UNIQUE): Glucagon receptor activation in the liver → increased hepatic lipid oxidation, enhanced thermogenesis, increased resting energy expenditure, enhanced ketogenesis. This third mechanism is what distinguishes retatrutide from tirzepatide and explains the HIGHEST WEIGHT LOSS ever recorded in an obesity drug trial.
The glucagon component creates a catabolic drive (energy expenditure) that complements the anabolic insulin effects and appetite suppression of GLP-1/GIP — a metabolic triple play.
Dosing Protocol
Low Dose
███ – ███ mcg/day
Standard Dose
███ mcg/day
High Dose
███ – ███ mcg/day
Dosing protocols are for paid members
Get exact dosing ranges, injection frequency, timing rationale, and reconstitution math.
Get Clinical Access — $79/moFrequency
Once weekly SubQ.
Half-Life
6 days
Reconstitution Guide
Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.
Unlock reconstitution guide →Clinical Warnings
Investigational — not approved anywhere.
GI side effects (nausea, diarrhea, vomiting).
Glucagon may raise glucose in some patients.
Thyroid C-cell tumor concern (GLP-1 class effect).
Pancreatitis risk.
Heart rate increase observed.
Contraindications
Absolute
Personal or family history of medullary thyroid cancer
MEN2 syndrome
Pregnancy
Pancreatitis
Relative Cautions
Type 1 diabetes
Gastroparesis
Gallbladder disease
Severe kidney disease
Side Effect Profile
Mild
- ●Nausea
- ●Mild diarrhea
- ●Injection site reaction
Moderate
- ●Vomiting
- ●Constipation
- ●Abdominal pain
- ●Increased heart rate
Severe (Rare)
- ●Pancreatitis
- ●Thyroid tumors (theoretical)
- ●Severe hypoglycemia with insulin
Synergistic Peptides
Common Stacks
Semaglutide
Tirzepatide
Research Status
PHASE II PUBLISHED, PHASE III ONGOING. PMID 37351655 (Jastreboff 2023 NEJM): Phase II — up to 24.2% body weight loss at 48 weeks. Highest weight loss recorded for anti-obesity medication. Phase III TRIUMPH trials ongoing.
Frequently Asked Questions
How does Retatrutide work?
Retatrutide is the first triple incretin receptor agonist, simultaneously activating GLP-1R, GIPR (glucose-dependent insulinotropic polypeptide receptor), and GcgR (glucagon receptor). GLP-1R: Appetite suppression, glucose-dependent insulin secretion, gastric emptying delay — same as semaglutide. GIPR: Potentiates insulin secretion, promotes adipose tissue remodeling and lipid handling — same addition as tirzepatide. GcgR (UNIQUE): Glucagon receptor activation in the liver → increased hepatic
What is the standard dose of Retatrutide?
Retatrutide dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Once weekly SubQ.
What is the half-life of Retatrutide?
The half-life of Retatrutide is 6 days. This determines optimal dosing frequency and timing.
Who should not use Retatrutide?
Retatrutide is absolutely contraindicated in: Personal or family history of medullary thyroid cancer; MEN2 syndrome; Pregnancy; Pancreatitis. Use with caution in: Type 1 diabetes; Gastroparesis; Gallbladder disease.
What are the side effects of Retatrutide?
Common mild side effects include: Nausea, Mild diarrhea, Injection site reaction. Moderate effects: Vomiting, Constipation, Abdominal pain, Increased heart rate.
What peptides stack well with Retatrutide?
Retatrutide is commonly stacked with: Semaglutide, Tirzepatide, AOD-9604.
How do you reconstitute Retatrutide?
Retatrutide is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.
How long should you cycle Retatrutide?
Retatrutide cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.
References & Citations
10 PubMed studies · 3 clinical trials
Medical Management of Obesity: A Comprehensive Review of Food and Drug Administration (FDA)-Approved and Investigational Therapies.
Raza Syed S, Zakir Zarshal, Hashmat Ahmad, Awan Saira K et al.. Cureus. 2025
The global rise in obesity has accelerated both clinical and pharmaceutical innovation in antiobesity pharmacotherapy. This narrative review synthesizes current evidence on Food and Drug Administratio
Diabetes Mellitus and Chronic Kidney Disease: The Future Is Being Surpassed.
Martínez-Castelao Alberto, Górriz José Luis, Fernández-Fernández Beatriz, Soler María José et al.. Journal of clinical medicine. 2025
Diabetes mellitus (DM) continues to be a global world health problem. Despite medical advances, both DM and chronic kidney disease (CKD) remain global health issues with high mortality and limited opt
Harnessing GLP-1 Receptor Agonists for Obesity Treatment: Prospects and Obstacles on the Horizon.
Abdelrahman Riad Mohammed, Musa Taha Hussein, Arbab Ismail Adam, Suliman Mohsen Hussein et al.. Journal of obesity. 2025
Obesity has emerged as a pressing global health challenge, and therapies based on glucagon-like Peptide 1 receptor agonists (GLP-1RAs) have transformed its management. Currently, liraglutide, semaglut
Gastrointestinal Adverse Effects of Anti-Obesity Medications in Non-Diabetic Adults: A Systematic Review.
Takrori Ehab, Peshin Supriya, Singal Sakshi. Medicina (Kaunas, Lithuania). 2025
Background: With rising obesity rates, pharmacological interventions are increasingly used in non-diabetic adults. While being effective in managing weight, these agents frequently cause gastrointesti
Engineered nutrient-stimulated hormonal multi-agonists for precision targeting of obesity and metabolic disorders.
Cho Yun Kyung, Jung Chang Hee. Clinical and molecular hepatology. 2025
Obesity and its related metabolic comorbidities, including type 2 diabetes, metabolic dysfunction-associated steatotic liver disease, and cardiovascular disease, are increasingly recognized as heterog
Perceived benefits of treatment for obesity with retatrutide: A qualitative study of patients in a phase 2 clinical trial.
Goetz Iris A, Kanu Chisom, Hoover Anastasia, Jimenez-Moreno Cecilia et al.. Obesity pillars. 2025
Retatrutide, an agonist of glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors, is in development for the treatment of obesity. We interviewed participants ex
Development and Content Evaluation of the Eating Behavior and Appetite Questionnaire (EBAQ) for Individuals with Obesity.
Kanu Chisom, Clucas Claudine, Skalicky Anne, Samuelson Ashley et al.. Advances in therapy. 2026
Obesity management medications can reduce body weight and have an impact on patients' appetite and eating behaviors. Existing patient-reported outcome (PRO) measures do not fully capture appetite and
Rationale, Design, and Baseline Characteristics of the TRANSCEND-CKD trial of Retatrutide in Patients with Chronic Kidney Disease.
Heerspink Hiddo J L, van Raalte Daniël H, Bjornstad Petter, Bunck Mathijs C et al.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2025
Retatrutide is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1, and glucagon receptors that reduced weight and HbA1c in individuals with obesity and type 2 diab
Registered Clinical Trials
A Safety Study of LY3437943 Given as a Single Injection in Healthy Participants
A Study of LY3437943 in Healthy Participants and Participants With Impaired Renal Function
A Study of LY3437943 in Chinese Participants With Obesity Or Overweight
Symptom Indications
Full Clinical Access
Complete Retatrutide Protocol
Access reconstitution math, cycle guides, drug interaction checker, stack builder with contraindication analysis, symptom checker, and downloadable PDF handouts.
Secure payment powered by Stripe.
This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.