Fat Loss on EZ Mode: The Ultimate Guide to Retratrutide

Chemical Names

LY-3437943

PubChem ID:171378578

Chemical Structure 

Research Applications 

• Fat Loss

• Obesity Management

• Metabolic Health

• Longevity

• Athletic Performance

• Cardiovascular Health

What is Retratrutide? 

Retratrutide is a synthetic peptide developed by Eli Lilly, designed to be the ultimate metabolic regulator.

Inspired by Semaglutide/Ozempic/Liraglutide/Dulaglutide (GLP-1 Agonists), and Tirzepatide (GLP-1/GIP agonist), this 39-amino acid peptide is a triple threat, targeting GIP, GLP-1 and glucagon (GCG) receptors.

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are incretin hormones that promote insulin secretion and regulate immune responses. The activation of the GCG receptors by Retratrutide boosts metabolic rate and increases energy expenditure.

Retratrutide demonstrates greater fat loss while sparing muscle mass compared to other GLP-1 agonists due to its unique triple agonism, leading to several distinct mechanisms:

Increases Fatty Oxidation and Energy Expenditure: Retratrutide's activation of the glucagon receptor increases energy expenditure and enhances fat oxidation, which results in more fat loss without reducing muscle mass, unlike semaglutide, liraglutide, dulaglutide, and tirzepatide, which mainly reduce fat through appetite suppression and lower energy intake

Anabolic & Muscle Sparing Properties: Enhances insulin secretion and insulin sensitivity through GIP receptor activation, which then improves IGF-1 activity downstream.

Another new addition to this class of peptides can be seen in the fatty acid component in its structure, which improves its stability and extends its duration of action in the body. This allows for a convenient once-weekly dosing schedule.

Eli Lilly is currently conducting the TRIUMPH phase-3 clinical program to assess retatrutide's safety and efficacy in treating obesity. These trials include participants both with and without type 2 diabetes (T2D). Preliminary findings have shown promising results in terms of both blood sugar management and weight reduction.

Sources: [1], [2], [3], [4], [5], [6]

Retratrutide is not FDA-approved, but is available to qualified researchers as reference material. 

Benefits in Research 

Weight Loss

As of 2024, the TRIUMPH program's phase 3 trials are investigating retatrutide's weight loss efficacy. Earlier studies have indicated body weight reductions of up to 24% from baseline.

The first human trial of Retratrutide, a proof-of-concept study, was conducted in Singapore in 2019. The phase I trial involved 47 participants receiving weekly doses ranging from 0.1 to 6 mg. The study suggested positive effects on appetite, food intake, and metabolic markers, with a favourable safety profile.

A subsequent 48-week phase II trial involved 338 non-diabetic adults with overweight or obesity. This larger study demonstrated dose-dependent weight reduction and improvements in cardiometabolic risk factors:

- 1 mg dose group: 8.7% weight reduction

- 4 mg group: 17.1% reduction

- 8 mg group: 22.8% reduction

- 12 mg group: 24.2% reduction

All participants receiving either 8 mg or 12 mg weekly experienced at least a 5% reduction in initial body weight. The study also noted significant improvements in waist circumference, blood pressure, glycated hemoglobin, fasting glucose, insulin levels, and most lipid levels (excluding HDL cholesterol).

Results from the 48 week phase II trial: 

Graph A-Weight loss over time: shows that higher doses of Retratrutide led to greater weight loss. The 12 mg dose resulted in the most significant weight loss (24.2%) by week 48. The lowest dose (1 mg) outperformed the placebo. Weight loss continued throughout the 48-week period for all Retratrutide doses. 

Graph B-shows the percentage of participants achieving various weight loss targets: 100% of participants on 8 mg and 12 mg doses achieved at least 5% weight loss. Higher doses consistently led to a greater percentage of participants achieving more substantial weight loss targets. For the 30% weight loss target, 26% of participants on the 12 mg dose achieved this, compared to 0% in the placebo group. 

1. Type II Diabetes Research

Earlier studies have shown promising results for Retratrutide’s potential for managing blood sugar and obesity in type II diabetes (T2D).

12-Week Phase 1b Trial:

• 72 adults aged 20-70 with T2D (baseline A1c levels between 7.0-10.5%) received retratrutide, dulaglutide (FDA-approved GLP-1 agonist), or placebo

• Highest dose (12 mg weekly) results by the end of the trial:

 • A1c decrease of up to 1.6%

 • Weight loss of up to 19.7 pounds (8.96 kg)

• Retatrutide outperformed both dulaglutide and placebo

36-Week Phase 2 Trial:

- 281 T2D patients received up to 12 mg of Retratrutide weekly

- 12 mg group results:

 • HbA1c reduction: 2.02% (22.07 mmol/mol) at 24 weeks, 2.16%(23.59 mmol/mol) at 36 weeks compared to 0.01% change in the placebo group

 • By the end of the trial, weight loss was dose-dependent, losing 16.94% of body weight at 36 weeks compared to 3% in the placebo

 • Improved lipid profiles: decreased triglycerides and non-HDL cholesterol

These trials demonstrate retatrutide's potential use for improvements in glycemic control, weight management, and cardiovascular risk factors in T2D patients, with dose-dependent effects observed.

UM’s Experience

I’ve just started my second run with retratrutide as my first one ended early due to injury. I’ve been seeing incredible results from just 1mg per week. The best way I can describe it is:

• Better appetite suppression than semaglutide, similar to Tirzepatide

• Food is a lot more enjoyable

• Cravings of all kinds, not just food, but even checking the crypto charts and doomscrolling cease to exist. (likely because GLP-1 receptors are located in areas like the ventral tegmental area and nucleus accumbens, which are key components of the brain's reward system)

• Better mental clarity, focus, and mood despite 1,000+ caloric deficit ( GIP receptors are also found in the brain and appear to influence energy metabolism, dopaminergic function, and mood regulation)

• Lifts are going up, muscles seem a bit more full than they’d normally be, and energy levels are great

• ZERO nausea, headaches, or lethargy that I’ve experienced on Semaglutide and liraglutide in the past

While the effects of Retratruide are dependent on the dose, diet, environment, lifestyle factors, and of course, genetics, I’m hearing very similar reports from others who have tried it.

Dosing

There are no official dosing guidelines for Retratrutide, but protocols typically begin with a low dose of 1mg per week, followed by a gradual increase if needed. Example:

Week 1-4: Starting dose of 1mg weekly 

Week 5-8: Increase to 2 mg weekly 

Week 9-12: Increase to 4 mg weekly 

Week 13-16: Increase to 8 mg weekly 

Week 17+: Reach the total dose of 12 mg weekly

Note: These dosage guidelines are based off of studies. Many individuals who aren’t diabetic or obese find that 1-2mg per week works for the entirety of the 8-16 fat loss cycle. Retatrutide is intended for weekly subcutaneous injection and hasn’t been researched in weekly dosages higher than 12mg. 

Side Notes

Retatrutide’s extended half-life allows for flexible administration - it can be injected at any time of day, regardless of meals before or after injection.

Clinical trials have favored the abdomen as the injection site, specifically recommending at least 2 inches (5 cm) from the navel (belly button). This placement reduces the likelihood of bruising, redness, infection, or irritation.

Research demonstrated that Retatrutide can be safely used over extended periods, with 48-week studies showing a safety profile similar to placebo and other incretin mimetics. 

This long-term approach suggests that Retatrutide is designed for continuous use without the need for cycling on and off. Consistent, ongoing treatment is key to achieving optimal weight management results and improving metabolic health.

Sources: [1], [2]

Ideal Stacks for Synergistic Fat Loss:

• Tesamorelin: Increases HGH secretion for enhanced fat loss and recovery

• AOD-9604: Increases fatty acid oxidation, enabling more fat to be burned during physical activity

• 5-Amino 1Mq: Inhibits NNMT, which is associated with increased mitochondrial function and greater energy expenditure. Appears to inhibit adipogenesis through the same pathway.

Side effects/ Risks 

A phase II study involving 338 non-diabetic participants revealed common side effects experienced by 62 participants who received the maximum weekly dose (of 12 mg):

• Nausea (45%)

• Vomiting: (19%)

• Constipation (16%)

• Diarrhoea: (15%)

• Cardiac arrhythmia (11%)

• Fatigue and early satiety: (10% each)

• Increased lipase levels (8%)

• Hepatic disorder (3% (2 participants))

• Pancreatitis: (2% (1 participant))

Serious adverse events occurred at similar rates in both Retatrutide and placebo groups (4% each). 

In the Retatrutide group, 1% experienced temporary elevations in alanine aminotransferase (ALT) levels exceeding three times the upper limit of normal.

While increases in amylase and lipase levels were observed, these were generally asymptomatic, with one exception of acute pancreatitis in the highest dose group.

Gastrointestinal side effects were the primary reason for treatment discontinuation. Dropout rates due to adverse effects in the treatment group ranged from 6% to 16%, depending on the Retatrutide dose.

Early results from phase I and II trials indicate that Retatrutide is generally well-tolerated. Its side effect profile appears similar to FDA-approved incretin mimetics like dulaglutide.

Best Source for Retratrutide

The majority of the peptide and research chemical companies out there are shady. Unfortunately, importing pre-manufactured products from Chinese vendors with little to no quality control, undesirable fillers and byproducts, lack of transparency/testing, and poor customer service is the industry standard. That’s why Limitless Biotech is my go-to source for peptides and research compounds:

• Unmatched Quality & Transparency: Limitless Life utilizes third-party lab tests, including HPLC-MS analysis, to guarantee that each batch of Retratrutide is of the highest purity (>99%) and potency.

• Fast Shipping: Limitless offers express shipping with a delivery promise of 24-48 hours, along with other shipping options for flexibility.

• Great Customer Service: Fast responses from helpful and knowledgeable individuals who truly care about their customers

• American Made: Limitless’s products are manufactured in a US-based GMP facility where meticulous sanitary processes and advanced purification processes are deployed to yield over 99% pure products every time.

• Best Bang for Your Buck: Coupon code BOWTIED gets you 15% off

Disclaimer: The content of this guide is for informational and educational purposes only and is not intended as medical advice. The information provided is based on personal experiences and research and should not be interpreted as an endorsement or recommendation for any specific treatment plan, product, or course of action. BowTied Biohacker is not a licensed medical professional, and his insights are not a substitute for professional medical advice, diagnosis, or treatment. Before making any changes to your medication regimen, starting new supplements, or experimenting with any drugs, it is important to consult with a qualified healthcare provider. Compounds in this post may be available for purchase for research purposes only. We do not condone the human use of research chemicals.This article may contains affiliate and coupon codes. We receive a commission on the links with referral codes and purchases made with coupon codes. Proceeds support the creation of new content.

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