Image 1 of 1
What It Is
Retatrutide is the most powerful weight loss peptide currently in clinical trials. It works by activating three different receptor systems at once: GLP-1, GIP, and glucagon. This triple action is why it produces better results than semaglutide or tirzepatide in head to head comparisons.
To put this in perspective, semaglutide hits one receptor and produces around 15% weight loss. Tirzepatide hits two receptors and produces around 21% weight loss. Retatrutide hits three receptors and in Phase 2 trials, participants lost an average of 24% of their body weight at the highest dose.
The compound was developed by Eli Lilly and is currently in Phase 3 trials. It is not yet FDA approved, but it is available through research peptide suppliers. Like the other incretin drugs, it is administered as a once weekly subcutaneous injection.
How It Works
To understand why retatrutide works so well, you need to understand what each receptor does.
GLP-1 Receptor
This is the same receptor that semaglutide targets. When activated, it reduces your appetite, slows down how fast food leaves your stomach, and improves how your body handles insulin. You feel full faster and stay full longer.
GIP Receptor
This receptor enhances insulin release and appears to improve how your body processes fat. Retatrutide is actually about 9 times more potent at this receptor than your body's natural GIP hormone. Tirzepatide also hits this receptor, which is part of why it outperforms semaglutide.
Glucagon Receptor
This is what sets retatrutide apart. Glucagon tells your body to release stored energy. When this receptor is activated, your body increases energy expenditure and ramps up fat burning in the liver. You are not just eating less, you are actually burning more calories.
The combination of all three means you eat less, digest slower, handle blood sugar better, and burn more energy. That is why the weight loss numbers are so much higher than single or dual receptor drugs.
Benefits
Highest Weight Loss in Any Drug Trial
At the 12 mg dose, participants in the Phase 2 trial lost an average of 24.2% of their body weight over 48 weeks. To put that in real numbers, if you weigh 250 pounds, that is about 60 pounds lost in under a year.
Nearly Everyone Responds
At the 8 mg and 12 mg doses, 100% of trial participants achieved at least 5% weight loss. At 12 mg, 93% lost at least 10% and 83% lost at least 15%. These response rates are higher than any other obesity drug.
Metabolic Health Improvements
In trials with type 2 diabetics, retatrutide reduced HbA1c by up to 2.0% while also producing significant weight loss. Blood pressure, triglycerides, and cholesterol markers also improved.
Increased Calorie Burn
Because of the glucagon receptor activation, retatrutide does not rely solely on appetite suppression. Your body actually burns more calories at rest. This may help with long term weight maintenance.
Once Weekly Dosing
The half life is approximately 6 days, so you only need to inject once per week.
What the Science Shows
Retatrutide has solid clinical trial data from Phase 1, 2, and ongoing Phase 3 studies.
Phase 2 Obesity Trial (2023)
This is the landmark study published in the New England Journal of Medicine. 338 adults with obesity received retatrutide at various doses or placebo for 48 weeks.
Results by dose:
• 1 mg weekly: 8.7% average weight loss
• 4 mg weekly: 17.1% average weight loss
• 8 mg weekly: 22.8% average weight loss
• 12 mg weekly: 24.2% average weight loss
• Placebo: 2.1% average weight loss
At the 12 mg dose, about 63% of participants lost at least 20% of their body weight, and roughly 25% lost 30% or more. Weight was still declining at week 48, which suggests longer treatment would produce even greater results.
Phase 2 Type 2 Diabetes Trial (2023)
Published in The Lancet. Participants with type 2 diabetes achieved approximately 17% weight loss at 36 weeks alongside major improvements in blood sugar control.
Starting Dose Matters
The trial tested starting at 2 mg versus 4 mg. Starting lower and escalating more slowly resulted in significantly fewer side effects with similar weight loss outcomes at 48 weeks. This is why the recommended protocol starts at 2 mg.
Sources:
• Jastreboff et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity." New England Journal of Medicine (2023)
• Rosenstock et al. "Retatrutide in type 2 diabetes." The Lancet (2023)
Dosing Protocol
Retatrutide requires a slow titration to minimize side effects. The protocol below is based on the Phase 2 trial design that showed the best tolerability.
Subcutaneous injection once weekly.
• Weeks 1 to 4: 2 mg
• Weeks 5 to 8: 4 mg
• Weeks 9 to 12: 8 mg
• Week 13 and onward: 12 mg (maximum dose)
Important Notes:
Starting at 2 mg instead of 4 mg makes a real difference in how you feel. The trial data showed significantly less nausea and GI distress with the slower start.
Many people get excellent results at 8 mg without ever needing 12 mg. If you are losing weight steadily and tolerating the dose well, there is no rule that says you must go to maximum.
If side effects are rough at any step, stay at that dose for another 4 weeks before increasing. There is no benefit to pushing through severe nausea.
Take your injection on the same day each week. Consistency matters.
Draw Volumes by Vial Size
All calculations assume reconstitution volumes that provide practical measurements on a standard insulin syringe.
10 mg Vial (2 mL reconstitution = 5 mg/mL)
Dose Volume Units on Syringe
──────────────────────────────────────────
2 mg 0.40 mL 40 units
4 mg 0.80 mL 80 units
6 mg 1.20 mL Requires two draws
8 mg 1.60 mL Requires two draws
Vial duration at 4 mg/week: 2.5 weeks
This concentration works best during the titration phase when you are using lower doses.
10 mg Vial (1 mL reconstitution = 10 mg/mL)
Dose Volume Units on Syringe
──────────────────────────────────────────
2 mg 0.20 mL 20 units
4 mg 0.40 mL 40 units
6 mg 0.60 mL 60 units
8 mg 0.80 mL 80 units
10 mg 1.00 mL 100 units (full syringe)
Vial duration at 8 mg/week: 1.25 weeks
20 mg Vial (2 mL reconstitution = 10 mg/mL)
Dose Volume Units on Syringe
──────────────────────────────────────────
2 mg 0.20 mL 20 units
4 mg 0.40 mL 40 units
8 mg 0.80 mL 80 units
10 mg 1.00 mL 100 units
12 mg 1.20 mL Requires two draws
Vial duration at 12 mg/week: about 1.7 weeks
Vial duration at 8 mg/week: 2.5 weeks
For the 12 mg dose, draw 100 units (10 mg), inject, then draw another 20 units (2 mg) and inject again.
Reconstitution Instructions
1. Draw the appropriate amount of bacteriostatic water into a sterile syringe (1 to 2 mL depending on vial size and desired concentration)
2. Inject slowly down the inside wall of the vial to avoid foaming
3. Gently swirl or roll the vial until fully dissolved. Do not shake.
4. Solution should be clear and colorless. Do not use if cloudy or contains particles.
5. Label with reconstitution date and concentration
6. Refrigerate at 36 to 46 degrees Fahrenheit (2 to 8 degrees Celsius)
7. Use within 28 days
Side Effects and Cautions
The side effects are similar to other incretin drugs, but the triple receptor activation means they can be more pronounced, especially if you titrate too fast.
Common Effects:
• Nausea (most common, affects 25 to 45% depending on dose)
• Diarrhea
• Vomiting
• Constipation
• Decreased appetite
• Feeling overly full
These are dose dependent. Starting at 2 mg and escalating slowly makes a significant difference. Most side effects improve after the first few weeks at each dose level.
Less Common:
• Increased heart rate (this peaked at week 24 in trials and then declined)
• Injection site reactions
• Fatigue
• Hair thinning (this is related to rapid weight loss, not the drug itself)
When to Contact a Medical Professional:
• Persistent vomiting that will not resolve
• Severe abdominal pain (could indicate pancreatitis or gallbladder issues)
• Signs of allergic reaction (rash, swelling, difficulty breathing)
• Resting heart rate consistently above 100 bpm
Who Should Avoid or Use With Care
Do not use if you have:
• Personal or family history of medullary thyroid carcinoma (MTC)
• Multiple endocrine neoplasia syndrome type 2 (MEN 2)
• Known hypersensitivity to retatrutide or similar compounds
• Current pregnancy or breastfeeding
Use with caution if you have:
• History of pancreatitis
• Gallbladder disease
• Type 1 diabetes
• Diabetic retinopathy (rapid improvements in blood sugar can temporarily worsen this)
• Heart rhythm issues
• Gastroparesis or other GI motility problems
Drug Interactions:
If you take insulin or sulfonylureas, those doses may need significant reduction to prevent low blood sugar. Retatrutide slows gastric emptying, which can affect how quickly oral medications are absorbed. Women using oral contraceptives should use backup methods during titration.
Success Tips
Start Slow
The most common mistake is titrating too fast. The 2 mg starting dose exists for a reason. Your body needs time to adapt to these signals.
Manage the Nausea
Eat smaller meals. Stop eating at the first sign of fullness. Avoid greasy, fried, or spicy foods during the titration phase. Stay upright after eating. Ginger tea helps.
Protect Your Muscle
With 24% weight loss possible, muscle preservation becomes critical. You need to prioritize protein at every meal. Aim for 1.0 to 1.2 grams per kilogram of body weight. Reduced appetite makes it easy to undereat protein, and if you do, you will lose muscle along with fat.
Stay Hydrated
These drugs can reduce your thirst signals. Set reminders to drink water. Dehydration makes nausea worse, causes constipation, and stresses your kidneys.
Keep Training
Walk daily. Lift weights 2 to 3 times per week. The glucagon component increases energy expenditure, so pairing this with exercise amplifies the effect. Do not rely on the drug alone.
Track Your Progress
Weigh yourself weekly at the same time. Take measurements monthly. Progress photos help. Weight was still declining at week 48 in the trials, so patience pays off.
Need Help With Nutrition or Training?
Peptides work best when paired with solid nutrition and training protocols. If you want structured guidance on preserving muscle mass during weight loss, dialing in your protein intake, or building a training program that supports your goals, check out website: turawellness.com
Injection Technique
1. Wash hands thoroughly with soap and water
2. Clean the vial stopper with an alcohol swab and allow to air dry
3. Draw the appropriate dose into a sterile insulin syringe
4. Clean the injection site with an alcohol swab
5. Pinch a skinfold and insert the needle at 45 to 90 degrees into subcutaneous tissue
6. Do not aspirate for subcutaneous injections
7. Inject slowly and steadily
8. Withdraw needle and apply light pressure with gauze if needed
9. Dispose of syringe immediately in a sharps container. Never recap needles.
10. Rotate injection sites weekly (abdomen, thighs, upper arms) at least 1 inch apart
Storage and Handling
Before Reconstitution:
• Store lyophilized (powder) vials in the freezer at minus 4 degrees Fahrenheit (minus 20 degrees Celsius)
• Can also be stored in the refrigerator at 36 to 46 degrees Fahrenheit
• Protect from light
• Do not use past expiration date
After Reconstitution:
• Refrigerate at 36 to 46 degrees Fahrenheit
• Use within 28 days
• Do not freeze after reconstitution
• Keep the stopper clean
• If solution becomes cloudy or contains particles, discard and use a new vial
Comparison to Other Weight Loss Compounds
Drug Receptors Max Dose Avg Weight Loss Status
────────────────────────────────────────────────────────────────────────────────────────────
Retatrutide GLP-1 + GIP + Gluc 12 mg weekly ~24% Phase 3
Tirzepatide GLP-1 + GIP 15 mg weekly ~21% Approved
CagriSema GLP-1 + Amylin 2.4/2.4 mg ~20% Phase 3
Semaglutide GLP-1 2.4 mg weekly ~15% Approved
Cagrilintide Amylin 2.4 mg weekly ~11% Phase 3
Liraglutide GLP-1 3.0 mg daily ~8% Approved
Retatrutide currently shows the highest weight loss of any obesity drug in clinical trials. The glucagon receptor adds something the others do not have: increased energy expenditure.
Legal Status
United States: Not FDA approved. Currently in Phase 3 clinical trials. Eli Lilly is the developer and regulatory submission is expected around 2026 if trials are successful.
Research Peptide Market: Retatrutide is available from research chemical suppliers in lyophilized powder form.
Future Outlook: If Phase 3 trials confirm the Phase 2 results, retatrutide could become the most effective obesity medication on the market. Potential availability is projected for late 2026 or 2027.
Frequently Asked Questions
How is retatrutide different from tirzepatide?
Tirzepatide activates GLP-1 and GIP receptors. Retatrutide adds a third: the glucagon receptor. This increases how many calories your body burns, which is why the weight loss numbers are higher.
Is 24% weight loss realistic?
That was the average at the 12 mg dose in the Phase 2 trial. Some people lost more, some lost less. Weight was still declining at week 48, so longer treatment would likely produce even greater results.
What if I miss a dose?
Take it as soon as you remember if it has been less than a few days. Otherwise skip and resume your regular schedule.
Will the weight come back if I stop?
Studies with other incretin drugs show weight regain after stopping. Long term or indefinite use may be necessary to maintain results. Building good habits during treatment helps reduce regain.
Is nausea unavoidable?
Most people experience some nausea, but starting at 2 mg instead of 4 mg significantly reduces severity. It typically improves after the first few weeks at each dose level.
Can I stack it with other peptides?
Retatrutide already activates three receptor pathways. Stacking with semaglutide or tirzepatidewould be redundant and increase side effects without adding benefit. If you want to add something, consider compounds that work through completely different mechanisms.
Does it raise heart rate?
Yes, dose dependent increases in heart rate were observed in trials. The effect peaked at 24 weeks and then declined. If you have heart rhythm issues, monitor closely.
Product Source
Research Grade Retatrutide available at turawellness.com
Disclaimer
This guide provides educational information about retatrutide based on published scientific literature and clinical trial data. This is for educational purposes only and does not constitute medical advice, diagnosis, or treatment. Retatrutide is an investigational compound that has not been approved by the FDA. Always consult qualified healthcare professionals before using any peptide or medication.
References
1. Jastreboff AM, et al. "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial." New England Journal of Medicine (2023)
2. Rosenstock J, et al. "Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes." The Lancet (2023)
3. Kaur M, Misra S. "A review of an investigational drug retatrutide." European Journal of Clinical Pharmacology (2024)
4. Li W, et al. "Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide." Cell Discovery (2024)
5. ClinicalTrials.gov. Retatrutide Phase 3 trials