Peptide Profile
Retatrutide
The world's first triple-action weight loss peptide that simultaneously activates three hormone receptors—GIP, GLP-1, and glucagon—delivering unprecedented weight loss results of up to 24% body weight in clinical trials.
Dose Range
1-12mg
Frequency
Once weekly
Route
Subcutaneous injection
Cycle Length
12+ weeks
Onset
Moderate (1-2 weeks)
Evidence
Moderate
Compound Profile
Scientific & Efficacy Data
C221H342N46O68
Molecular Formula
4731 g/mol
Molecular Weight
~6 days (allows once-weekly dosing)
Half-Life
High via subcutaneous injection
Bioavailability
2381089-83-2
CAS #
171390338
PubChem ID ↗
Developed By · 2020
Tamer Coskun and team
Eli Lilly and Company
Primary Benefits
Delivers the highest weight loss ever recorded in Phase 2 obesity trials—up to 24% body weight reduction at the 12mg dose
Dramatically improves blood sugar, HbA1c, and metabolic markers through triple receptor activation
Powerfully reduces hunger and cravings through multiple brain pathways, making dietary changes feel natural
Amino Acid Sequence
Tyr-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-Aib-Leu-Asp-Lys-Ile-Ala-Gln-Gln-Ala-Phe-Val-Gln-Trp-Leu-Ile-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-Lys(C20 diacid)-NH2Dosing
How much
do I take?
Starting Dose
1-2 mg
Start low to let your body adjust. This minimizes the nausea and GI side effects that are most common when starting. Even at this low dose, you'll likely notice reduced appetite.
Standard Dose
4-8 mg
The sweet spot for most users. Clinical trials showed substantial weight loss at these doses with manageable side effects. Increase gradually (every 4 weeks) to reach this range.
Advanced Dose
12 mg
Maximum studied dose delivering the most dramatic results—up to 24% weight loss. Only reach this after gradual titration and proving tolerance at lower doses. Side effects are more common but still manageable for most.
Timing
Best time to take
Pick any consistent day each week—what matters most is doing it the same day each week. Many people choose weekend mornings so any initial nausea happens when they can rest.
With food?
Inject regardless of food timing. However, eating slowly and avoiding large, fatty meals helps minimize nausea. Many users find eating smaller, more frequent meals works better on this medication.
If stacking
Do not combine with other GLP-1 agonists like semaglutide or tirzepatide—retatrutide already hits all three receptors. Metformin is safe and often beneficial to continue.
Adjusting Your Dose
Increase if
- +You've been on current dose for 4+ weeks with good tolerance
- +Weight loss has plateaued and you're below target
- +GI side effects have resolved or become minimal
- +Your healthcare provider recommends escalation
Decrease if
- -Nausea or vomiting is persistent and interfering with daily life
- -You're losing weight too rapidly (more than 3 lbs/week consistently)
- -GI side effects don't improve after 2-3 weeks on current dose
- -You experience hypoglycemia symptoms
Signs of right dose
- ✓Steady weight loss of 1-2 lbs per week
- ✓Reduced appetite without severe nausea
- ✓Improved energy levels
- ✓Blood sugar levels stabilizing (if diabetic)
Dosing Calculator
Calculate Your Exact Dose
Amount to Draw
10
units
Suitability
Is this
right for me?
Best For
Significant Obesity Management
If you need to lose a substantial amount of weight, retatrutide is showing unprecedented results. Phase 2 trials demonstrated average weight loss of 24% at the highest dose—that's nearly 60 pounds for someone weighing 250 lbs. No other medication has matched this.
Type 2 Diabetes with Obesity
Retatrutide tackles both problems at once. It dramatically improves blood sugar control (HbA1c reductions of up to 2%) while delivering major weight loss. The dual benefit makes it especially valuable for diabetics struggling with weight.
Metabolic Syndrome Warriors
If you're dealing with the cluster of issues that includes high blood sugar, excess belly fat, abnormal cholesterol, and high blood pressure, retatrutide's triple mechanism attacks multiple aspects of metabolic dysfunction simultaneously.
Fatty Liver Disease (MASLD)
Early research shows retatrutide may significantly reduce liver fat. For people with non-alcoholic fatty liver disease, this peptide offers hope through weight loss plus direct metabolic improvements that benefit liver health.
Consider Alternatives If
Who Should Avoid
Do not use if
- ×You have a personal or family history of medullary thyroid carcinoma—this is a serious contraindication for all GLP-1 class medications
- ×You have Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- ×You are pregnant or planning to become pregnant—stop at least 2 months before conception
- ×You have a history of severe pancreatitis or active gallbladder disease
- ×You've had a serious allergic reaction to GLP-1 agonists
- ×You have severe gastroparesis or other serious GI motility disorders
Use with caution if
- !You take insulin or sulfonylureas—dose adjustments needed to prevent low blood sugar
- !You have a history of depression or suicidal thoughts—monitor mental health closely
- !You have diabetic retinopathy—rapid blood sugar improvements can temporarily worsen it
- !You have kidney problems—monitoring may be needed
- !You take oral medications with narrow absorption windows—GI slowdown may affect absorption
- !You have history of eating disorders—appetite suppression effects need monitoring
Administration
How do I
use it?
Reconstitution
What you need
- •Pre-filled pen or vial of retatrutide (as supplied)
- •Insulin syringes (29-31 gauge) if using vials
- •Alcohol swabs for injection site cleaning
- •Sharps disposal container
Injection
Route
Subcutaneous injection (just under the skin)—the same easy technique used for insulin
Best sites
- •Abdomen (at least 2 inches away from belly button)
- •Front of thighs (middle area)
- •Back of upper arms (have someone help if needed)
Technique
- 1.Wash hands thoroughly with soap and water
- 2.Clean the injection site with an alcohol swab and let it dry completely
- 3.Pinch a fold of skin at the injection site
- 4.Insert the needle at a 45-90 degree angle (90 degrees if you have adequate subcutaneous tissue)
- 5.Inject the medication slowly over 5-10 seconds
- 6.Remove the needle and apply gentle pressure—don't rub
Storage
Signs of degradation
Sample Daily Schedule
Safety
Is it
safe?
Safety Profile
Retatrutide has shown a generally favorable safety profile in Phase 1 and Phase 2 clinical trials involving over 600 participants. Most side effects are gastrointestinal and tend to improve over time. The medication appears well-tolerated when doses are increased gradually. No major safety signals have emerged, but larger Phase 3 trials are still ongoing.
Current safety data comes from Phase 1 and Phase 2 trials conducted by Eli Lilly. Multiple Phase 3 trials are currently underway to establish long-term safety in larger populations. As a research compound not yet FDA approved, the full safety profile is still being established.
Common Side Effects
Experienced by some users
Nausea
The most frequently reported side effect, especially during dose escalation. Your gut has lots of GLP-1 receptors, and they need time to adjust.
Management: Start with lower doses and increase gradually. Eat smaller meals, avoid fatty foods, and stay hydrated. Usually improves significantly after the first few weeks.
Diarrhea
Common in the first weeks of treatment as your digestive system adapts to the medication's effects on gut motility.
Management: Stay well hydrated. Avoid greasy, spicy, or high-fiber foods initially. Usually resolves within 2-4 weeks as your body adjusts.
Constipation
Some users experience the opposite—slowed digestion can lead to constipation, especially at higher doses.
Management: Increase water intake significantly. Add fiber gradually. Gentle physical activity helps. Over-the-counter remedies are safe if needed.
Decreased appetite
This is actually the intended effect! But it can feel strange at first when you realize you're simply not hungry.
Management: This is generally positive but ensure you're still eating nutritious foods. Don't skip meals entirely—aim for smaller, protein-rich meals.
Less Common
- •Increased heart rate
- •Injection site reactions
These typically resolve with continued use or dose adjustment.
Stop and Seek Help If
- ×Severe or persistent abdominal pain (possible pancreatitis)—seek emergency care
- ×Signs of allergic reaction: rash, swelling, difficulty breathing
- ×Persistent severe nausea or vomiting that doesn't improve with dose reduction
- ×Symptoms of gallbladder problems (right upper abdominal pain)
- ×Symptoms of severe hypoglycemia that recur despite medication adjustments
- ×Any concerning mental health changes
Retatrutide is an investigational medication currently in clinical trials. It is not FDA approved. Any use should be under the supervision of a qualified healthcare provider. Never start, stop, or change your dose without medical guidance.
Interactions
With other peptides
- !Do NOT combine. Both target the GLP-1 receptor—using them together provides no additional benefit and increases side effects.
- !Do NOT combine. Retatrutide already hits both GIP and GLP-1 receptors that tirzepatide targets, plus glucagon.
- ✓Limited interaction data. Theoretically safe as they work through different mechanisms, but use caution.
- ✓No direct interaction known. Some users stack for body composition, but data is limited.
With medications
- !Insulin - High interaction risk. Retatrutide dramatically lowers blood sugar—insulin doses typically need significant reduction (20-50%) to prevent hypoglycemia.
- !Sulfonylureas (glipizide, glyburide) - Increased hypoglycemia risk. These drugs also stimulate insulin release. Dose reduction usually needed.
- ✓Metformin - Safe and often beneficial combination. Metformin works through different mechanisms and complements retatrutide well.
- ✓SGLT2 inhibitors (empagliflozin, dapagliflozin) - Generally safe combination used in clinical trials. Both promote weight loss through different mechanisms.
- ✓Oral contraceptives - Slowed GI transit may affect absorption. Consider using backup contraception or switch to non-oral methods.
- ✓Levothyroxine - Take thyroid medication at least 30-60 minutes before retatrutide or 4 hours after. GI slowing may affect absorption.
With supplements
- ✓Vitamin B12 - GLP-1 agonists may reduce B12 absorption over time. Consider supplementation, especially long-term.
- ✓Protein supplements - Safe and often helpful to maintain adequate protein intake while eating less overall.
- ✓Fiber supplements - Safe but start slowly. Can help with constipation but may worsen early GI symptoms if added too quickly.
- ✓Multivitamins - Safe and recommended. When eating less food, ensuring micronutrient adequacy is important.
Effectiveness
Does it
work?
Evidence Level
Moderate human trials
What to Expect
Weeks 1-4
What you might notice
- •Reduced appetite—you may feel full faster than usual
- •Some nausea, especially after larger meals
- •Possible early weight loss (3-5 lbs in the first month)
- •Changes in food preferences—some cravings may diminish
- •Mild GI symptoms as your body adjusts
What's normal
- •Mild to moderate nausea that improves between doses
- •Eating smaller portions without feeling deprived
- •Some trial and error finding foods that sit well
What's next
- →Stay consistent with your weekly injection schedule
- →Prepare for potential dose increase after 4 weeks
- →Focus on protein-rich, nutrient-dense foods
Weeks 5-12
What you might notice
- •More significant weight loss becoming visible
- •GI side effects generally improving
- •Improved blood sugar levels if diabetic
- •Sustained appetite control between doses
- •Increased energy as you lose weight
What's normal
- •Steady weight loss of 1-2 lbs per week
- •Needing smaller meals to feel satisfied
- •Side effects diminishing as your body adapts
What's next
- →Continue gradual dose increases as tolerated
- →Incorporate regular physical activity if not already
- →Track your progress—weight, measurements, how clothes fit
Weeks 13-24
What you might notice
- •Substantial weight loss—trials showed 17-18% average at 24 weeks on higher doses
- •Significant improvements in metabolic markers
- •Better fitting clothes, visible body changes
- •Improved mobility and physical comfort
- •Blood sugar and blood pressure often improving
What's normal
- •Continued weight loss though rate may slow slightly
- •Feeling adapted to the medication
- •New eating habits becoming routine
What's next
- →Discuss long-term plans with your healthcare provider
- →Continue healthy lifestyle habits to maintain results
- →Monitor for any new or worsening side effects
Weeks 24-48+
What you might notice
- •Maximum weight loss effects—up to 24% body weight in trials
- •Dramatic improvements in metabolic health markers
- •Possible reduction in other medications (diabetes, blood pressure)
- •Transformed body composition
- •Stabilization at new, lower weight
What's normal
- •Weight loss gradually plateauing as you approach new set point
- •Feeling like this is your 'new normal' for eating
- •Long-term side effects minimal for most users
What's next
- →Work with your provider on maintenance strategy
- →Maintain healthy lifestyle habits established during treatment
- →Consider long-term medication plans as Phase 3 data emerges
Signs It's Working
Weight Loss Indicators
- ✓Scale weight decreasing consistently over weeks
- ✓Clothes fitting more loosely
- ✓Visible changes in face, neck, and waist
- ✓Reduced waist circumference
- ✓Lower body mass index (BMI)
Appetite and Eating Changes
- ✓Feeling full faster during meals
- ✓Reduced food cravings, especially for high-calorie foods
- ✓Going longer between meals without hunger
- ✓Smaller portions feeling satisfying
- ✓Less mental preoccupation with food
Metabolic Improvements
- ✓Lower fasting blood sugar levels
- ✓Improved HbA1c (if diabetic)
- ✓Better cholesterol numbers on blood tests
- ✓Reduced blood pressure
- ✓Lower liver enzymes (fatty liver improvement)
Quality of Life
- ✓Increased energy and less fatigue
- ✓Improved mobility and easier physical activity
- ✓Better sleep quality
- ✓Increased confidence and mood improvement
- ✓Reduction in weight-related joint pain
Not Seeing Results?
Common reasons
- •Dose too low—retatrutide shows strong dose-dependent effects; significant weight loss typically requires 4mg+ doses
- •Not enough time—real transformation takes 24-48 weeks; don't expect dramatic results in the first month
- •Eating through the appetite suppression—some people need to consciously honor the reduced hunger rather than eating out of habit
- •Poor injection technique—ensure full dose is actually administered subcutaneously
- •Missing doses—weekly dosing requires consistency; missed doses reduce effectiveness
- •Underlying metabolic conditions not addressed—thyroid issues or other hormonal imbalances may need separate treatment
Key Research
"Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial"
Jastreboff AM, Kaplan LM, Frías JP et al., 2023
Finding: In 338 adults with obesity, retatrutide produced dose-dependent weight loss up to 24.2% at 48 weeks with the 12mg dose—the highest ever recorded for any anti-obesity medication in a Phase 2 trial. Even the lowest dose (1mg) outperformed placebo.
View Study"A review of an investigational drug retatrutide, a novel triple agonist agent for the treatment of obesity"
Kaur M, Misra S, 2024
Finding: This comprehensive review confirmed retatrutide's unique triple-receptor mechanism offers advantages over single or dual agonists. The glucagon receptor activation may contribute additional energy expenditure and fat burning not seen with GLP-1-only drugs.
View Study"Efficacy and safety of triple hormone receptor agonist retatrutide for the management of obesity: a systematic review and meta-analysis"
Tewari J, Qidwai KA, Tewari A et al., 2025
Finding: Pooled analysis of all available trials confirmed retatrutide shows a clear dose-response relationship for weight loss. The safety profile was comparable to placebo for serious adverse events, with GI symptoms being the main tolerability concern.
View Study"Effects of retatrutide on body composition in people with type 2 diabetes"
Coskun T, Wu Q, Schloot NC et al., 2025
Finding: Detailed body composition analysis showed retatrutide users lost primarily fat mass while preserving lean muscle mass better than typically seen with dieting alone—crucial for long-term metabolic health.
View Study"Triple Agonism Based Therapies for Obesity"
Goldney J, Hamza M, Surti F, 2025
Finding: This review placed retatrutide in context of the obesity medication landscape, noting its triple mechanism represents a new frontier in metabolic pharmacotherapy with potential to address multiple aspects of metabolic disease simultaneously.
View StudyFrequently Asked Questions