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Retatrutide
(LY3437943)
What if there was one weekly injection that crushed your appetite, burned fat faster than Ozempic, and reversed liver damage - all in under a year? There is. It’s called Retatrutide. This isn't anything like your typical weight loss drugs. This is a molecule that mogs semaglutide, tirzepatide, and even your expectations.
What is Retatrutide
Retatrutide is a triple glucagon hormone receptor agonist (GLP-1, GIP, and GCGR receptors). (1)
Mechanism of Action | Receptor | Effect | Role |
| GLP-1 | Increases insulin, reduces appetite | Suppresses hunger, improves glucose control |
| GIP | Enhances insulin release | Amplifies GLP-1 and metabolic flexibility |
| GCGR | increases the amount of energy used | Promotes fat oxidation, thermogenesis, reduces liver fat |
Unlike semaglutide (GLP-1 only) or tirzepatide (GLP-1 + GIP), Retatrutide adds glucagon activation for active fat burn rather than passive appetite suppression.
More Info
Retatrutide is currently on phase 3 trials and is not FDA approved yet. You probably have heard about reta by now because it's so good. It’s the strongest fat-loss drug ever studied so far compared to Semaglutide and Tirzepatide (Mounjaro).
| Drug | Avg Weight Loss | Duration |
 Retatrutide | ~24.2% | 48 Weeks |
 Tirzepatide | ~20.9% | 72 Weeks |
 Semaglutide | ~14.9% | 68 Weeks |
Trial (1), (2), (3)
Most fat-loss drugs just make you eat less. But Retatrutide doesn’t just help you eat less - it can raise your baseline calorie burn, even when you’re doing nothing. That’s because activating the glucagon receptor increases energy expenditure.
the extreme appetite suppression can make you easy to undereat, which mean it can cause nutrient deficiencies or muscle loss if you’re not careful. That’s why you should watch your protein intake and strength training if your'e on reta. Reta isn't only for weight loss, it improves your health too.
Most fat-loss drugs just make you eat less. But Retatrutide doesn’t just help you eat less - it can raise your baseline calorie burn, even when you’re doing nothing. That’s because activating the glucagon receptor increases energy expenditure.
the extreme appetite suppression can make you easy to undereat, which mean it can cause nutrient deficiencies or muscle loss if you’re not careful. That’s why you should watch your protein intake and strength training if your'e on reta. Reta isn't only for weight loss, it improves your health too.
Retatrutide Benefits
Clinical Benefits
Lipid & Cholesterol Improvements:
Optimal Dosage & Titration Protocol
There is no one size fits all optimal dose.
Instead, use a titration protocol that balances fat loss with tolerability.
(Sourced from NEJM 2023 Trial: NCT04881760) (1)
Tips
- Fat loss
- Appetite Suppression & Cravings Elimination
- Increased Energy Expenditure
- Blood Sugar & Insulin Optimization
- Liver Fat Reduction & MASLD Therapy
- Cardiometabolic Health Boost
- Cholesterol & Lipid Profile Improvements
Clinical Benefits
Area | Effect |
Weight Loss | Up to 24.2% body weight loss in 48 weeks (12mg group, NEJM 2023) |
Liver Fat | 81–86% liver fat reduction in MASLD patients |
Insulin Sensitivity | ↑ significantly, even in non-diabetics |
Appetite Control | Strong but slightly less "fullness" vs semaglutide |
Tolerability | Better than GLP-1s alone, lower dropout in trials |
Lipid & Cholesterol Improvements:
Marker | Change |
| Triglycerides | ↓ 41.6% |
| LDL Cholesterol | ↓ 12–15% |
| HDL | ↔ Neutral or slight ↓ |
| Liver Fat | ↓ 81-86% |
| ApoC-III | ↓ ~48% |
Optimal Dosage & Titration Protocol There is no one size fits all optimal dose.
Instead, use a titration protocol that balances fat loss with tolerability.
The titration protocol is just a step-by-step way to increase the dose of a compound gradually. Think of it like turning up the volume on a speaker. You don’t blast it to max immediately. You increase it slowly until it’s just right.
Dosing Strategy: Start low: 2mg/week.
Increase every 4–6 weeks based on progress and tolerability. Stop when results plateau or sides worsen
Dosing Strategy: Start low: 2mg/week.
Increase every 4–6 weeks based on progress and tolerability. Stop when results plateau or sides worsen
Week | Dose (mg/week) |
0-4 | 2.0 mg |
4-8 | 4.0 mg |
8-16 | 8.0 mg |
16-36+ | 12.0 mg |
Tips
1. Start in Low Dosage and Titrate Slowly
Start with 2 mg per week, and only increase it every 4–6 weeks if your body’s handling it well. Don’t rush to 12 mg just because someone on Reddit did.
Why this matters:
Retatrutide is strong - it hits 3 hormone systems in 1 (GLP-1, GIP, and glucagon). If you take too much too fast, your body might freak out. Nausea, diarrhea, and digestive issues.
2. Prioritize High Protein Intake
Eat 1.6–2.4 g/kg bodyweight/day of protein. Retatrutide causes extreme fat loss - up to 24.2% in trials!! - which can also lead to muscle loss if you're under-eating protein. Higher protein intake enhances satiety and thermogenesis, which synergizes with GLP-1 action and enhances GIP signaling.
3. Don't Forget to Eat - Especially Real Food
Retatrutide works so well at suppressing appetite, some people barely eat. It may sound great at first, but if you go weeks under-eating, your body will become deficient in the nutrients it needs to function. Prioritize whole foods like meat, eggs.
4. Track Your Biomarkers
Run blood panels every month or two. Watch your cholesterol, liver enzymes, blood sugar, and kidney function. Retatrutide improves most of these things — but everyone reacts differently. It's important you're not only getting leaner, but healthier as well. Bloodwork keeps you honest. It helps you find problems early, adjust your dosage, and, if necessary, modify your diet.
Focus on
Start with 2 mg per week, and only increase it every 4–6 weeks if your body’s handling it well. Don’t rush to 12 mg just because someone on Reddit did.
Why this matters:
Retatrutide is strong - it hits 3 hormone systems in 1 (GLP-1, GIP, and glucagon). If you take too much too fast, your body might freak out. Nausea, diarrhea, and digestive issues.
2. Prioritize High Protein Intake
Eat 1.6–2.4 g/kg bodyweight/day of protein. Retatrutide causes extreme fat loss - up to 24.2% in trials!! - which can also lead to muscle loss if you're under-eating protein. Higher protein intake enhances satiety and thermogenesis, which synergizes with GLP-1 action and enhances GIP signaling.
3. Don't Forget to Eat - Especially Real Food
Retatrutide works so well at suppressing appetite, some people barely eat. It may sound great at first, but if you go weeks under-eating, your body will become deficient in the nutrients it needs to function. Prioritize whole foods like meat, eggs.
4. Track Your Biomarkers
Run blood panels every month or two. Watch your cholesterol, liver enzymes, blood sugar, and kidney function. Retatrutide improves most of these things — but everyone reacts differently. It's important you're not only getting leaner, but healthier as well. Bloodwork keeps you honest. It helps you find problems early, adjust your dosage, and, if necessary, modify your diet.
Focus on
- Liver function (ALT, AST)
- Lipids (LDL, HDL, triglycerides)
- HbA1c / fasting glucose
- Creatinine / eGFR (kidney)
Side Effects
- Nausea (50–60%)
- Diarrhea (30–40%)
- Constipation
- Vomiting
The side effects are dose-related.
How to mitigate:- Eat smaller meals more frequently.
- Avoid greasy, spicy, or high-fat meals (this can delay gastric emptying).
- Make sure you're not under eating (read the tips part)
- Ginger, peppermint tea, or digestive enzymes may help.
Studies
investor.lilly.com
pmc.ncbi.nlm.nih.gov
pmc.ncbi.nlm.nih.gov
www.sciencedirect.com
www.sciencedirect.com
en.wikipedia.org
pmc.ncbi.nlm.nih.gov
www.axios.com
www.nature.com
Lilly's phase 2 retatrutide results published in The New England Journal of Medicine show the investigational molecule achieved up to 17.5% mean weight reduction at 24 weeks in adults with obesity and overweight | Eli Lilly and Company
The Investor Relations website contains information about Eli Lilly and Company's business for stockholders, potential investors, and financial analysts.
Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials - PMC
Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without ...
pmc.ncbi.nlm.nih.gov
Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease - PMC
Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease (MASLD), the absence of licensed medications is striking. A deeper understanding of the heterogeneous nature of MASLD has recently ...
pmc.ncbi.nlm.nih.gov
The power of three: Retatrutide's role in modern obesity and diabetes therapy
The increasing prevalence of obesity and type 2 diabetes mellitus has resulted in a significant challenge to public health throughout the globe. It re…
The Effect of Retatrutide on Kidney Parameters in Participants With Type 2 Diabetes Mellitus and/or Obesity
Obesity and type 2 diabetes mellitus (T2D) increase the risk of kidney disease. This study assessed changes in kidney parameters with retatrutide, an …
Retatrutide - Wikipedia
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial - PMC
Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and ...
pmc.ncbi.nlm.nih.gov
Eli Lilly weight-loss drug shows extraordinary promise
Trial patients lost an average of 58 pounds after 48 weeks.
Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial - Nature Medicine
Phase 2 clinical trial results show that retatrutide, a triple agonist of the GIP, GLP-1 and glucagon receptors, results in up to 82% reduction in liver fat.
www.nature.com
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