Looking for Retatrutide experiences

[t_spacemonkey]

tldr; absolutely the best weight loss peptide IMHO to date

I want to summarize my early exp. with retatrutide. I could not handle any semaglutide in the past, even 0.1mg gave me hellish nausea and lethargy. but R. is different.
- 2 weeks ago I started a protocol, 2mg/week, divided in 2 injections.
- absolutely no nausea or lethargy, if anything a good energy boost
- significant appetite reduction, but you can still eat, to give you an example, my typical lunch would be normally 400g ground beef, i can do 150g and can pretty full.
- a bit harder to hit protein levels
- diet shifted more towards carbs then fat (hard time eating a lot of meat)
- body burns very fast through carbs. had to shift diet towards rice/potatoes/meat+some fruit

downsides:
- sugar cravings can be real, and I did exp. some hypoglycemia (55 blood glucose) after gym workouts. managing diet is a bit more tricky, if you workout a lot (me), but it does not cause you energy to dive whatsoever.


--------------------------------

From admin.:

Retatrutide - A Game Changer in Obesity Pharmacotherapy

Understanding the Obesity Challenge​

Obesity has become one of the most pressing health challenges of our time. It's not just about weight—excess body fat increases the risk of type 2 diabetes, heart disease, stroke, certain cancers, and numerous other health problems. For decades, the primary treatments have been lifestyle changes (diet and exercise), bariatric surgery, and medications that often produced modest results with significant side effects.

The landscape began shifting dramatically with newer medications like semaglutide (Wegovy) and tirzepatide (Mounjaro/Zepbound), which showed unprecedented weight loss results. Now, retatrutide is emerging as potentially the most powerful obesity medication yet developed.

What Makes Retatrutide Different?​

Retatrutide is a triple agonist—meaning it activates three different hormone receptors simultaneously:

GLP-1 (Glucagon-Like Peptide-1): This hormone slows stomach emptying, reduces appetite, and helps regulate blood sugar

GIP (Glucose-Dependent Insulinotropic Polypeptide): This hormone enhances insulin release and may affect fat metabolism

Glucagon: This hormone increases energy expenditure and promotes fat burning

Think of it like conducting an orchestra with three sections instead of one or two. While semaglutide works on GLP-1 alone and tirzepatide works on both GLP-1 and GIP, retatrutide adds glucagon to the mix, creating a more comprehensive metabolic response.

The Clinical Trial Results​

The results from Phase 2 clinical trials have been nothing short of remarkable:

Weight Loss Outcomes​

In the landmark 48-week study published in The New England Journal of Medicine, participants taking the highest dose of retatrutide (12 mg weekly) lost an average of 24.2% of their body weight. To put this in perspective:

A person weighing 250 pounds could lose about 60 pounds

This approaches the weight loss typically seen with bariatric surgery (25-30%)

Nearly half of participants (47%) lost at least 25% of their body weight

Some participants lost over 30% of their body weight

For comparison:

Lifestyle changes alone typically produce 3-5% weight loss

Older obesity medications averaged 5-10% weight loss

Semaglutide (Wegovy) produces about 15% weight loss

Tirzepatide (Zepbound) produces about 20-22% weight loss

Metabolic Benefits Beyond Weight Loss​

Retatrutide didn't just reduce weight—it improved virtually every metabolic parameter measured:

Blood Sugar Control: Participants with prediabetes or diabetes saw dramatic improvements in their hemoglobin A1c levels (a measure of average blood sugar over time). Many people with type 2 diabetes achieved normal blood sugar levels without diabetes medications.

Cardiovascular Risk Factors: The medication significantly reduced:

Blood pressure (both systolic and diastolic)

Triglycerides (blood fats linked to heart disease)

LDL cholesterol ("bad" cholesterol)

Liver fat (important for preventing fatty liver disease)

Body Composition: Unlike simple calorie restriction, which can cause significant muscle loss, retatrutide appeared to preferentially reduce fat mass while better preserving lean muscle tissue. This is crucial because maintaining muscle helps sustain metabolic rate and physical function.

How Does It Actually Work?​

The mechanism of action is multifaceted and elegant:

Appetite Suppression​

The GLP-1 and GIP components work on brain centers that control hunger and satiety. People taking retatrutide report:

Feeling full much sooner when eating

Reduced food cravings, especially for high-calorie foods

Decreased preoccupation with food

Natural portion control without feeling deprived

Slowed Gastric Emptying​

The medication slows how quickly food leaves the stomach, creating prolonged feelings of fullness. This means you feel satisfied longer after meals, naturally reducing calorie intake throughout the day.

Enhanced Energy Expenditure​

The glucagon component is particularly interesting. Glucagon increases your metabolic rate—essentially helping your body burn more calories at rest. It also promotes the breakdown of stored fat for energy and may enhance fat oxidation during physical activity.

Improved Insulin Sensitivity​

The combination of weight loss and direct hormonal effects improves how your body responds to insulin. This means your cells can better utilize glucose for energy rather than storing it as fat, creating a positive metabolic cycle.

The Patient Experience​

Administration​

Retatrutide is given as a once-weekly subcutaneous injection (under the skin), similar to insulin but much less frequent. The injection uses a small, thin needle and most people find it relatively painless. The medication is started at a low dose and gradually increased over several months to minimize side effects.

Side Effects​

Like other GLP-1-based medications, the most common side effects are gastrointestinal:

Common (but usually temporary):

Nausea (the most frequent complaint)

Diarrhea

Constipation

Vomiting

Abdominal discomfort

These effects are typically worst when starting the medication or increasing the dose, and they usually improve over time as the body adjusts. Starting with a low dose and increasing slowly helps minimize these issues.

Less Common but Important:

Reduced appetite (which is actually the desired effect, but can be too strong for some)

Fatigue during the adjustment period

Potential gallbladder issues with rapid weight loss

Rare cases of pancreatitis (inflammation of the pancreas)

Who Shouldn't Take It​

Based on clinical trial data and the medication's mechanism, retatrutide is not appropriate for:

People with a personal or family history of medullary thyroid cancer

Those with Multiple Endocrine Neoplasia syndrome type 2

Pregnant or breastfeeding women

People with a history of severe pancreatitis

Those with severe gastroparesis (stomach paralysis)

Comparing Retatrutide to Other Options​

Versus Lifestyle Changes Alone​

While diet and exercise remain fundamental to health, many people struggle to achieve significant, sustained weight loss through lifestyle changes alone. The average person loses about 3-5% of their body weight with intensive lifestyle programs—important, but often insufficient for people with obesity-related health problems. Retatrutide's 24% average weight loss represents a quantum leap in effectiveness.

Versus Other Medications​

Semaglutide (Wegovy): A single GLP-1 agonist producing about 15% weight loss. Retatrutide's triple mechanism appears to produce 60% more weight loss.

Tirzepatide (Zepbound): A dual GLP-1/GIP agonist producing about 20-22% weight loss. Retatrutide's addition of glucagon activation adds another 2-4% weight loss on average, with some individuals responding even more dramatically.

Older medications (orlistat, phentermine, etc.): These produce 5-10% weight loss with various limitations. Retatrutide is in a completely different league.

Versus Bariatric Surgery​

Bariatric surgery remains the gold standard for severe obesity, producing 25-35% weight loss that can be maintained long-term. Retatrutide's 24% average weight loss approaches surgical results without the risks, recovery time, and permanence of surgery. However, surgery has decades of long-term data, while retatrutide is still in clinical trials.

The key question is whether retatrutide's effects can be maintained long-term and what happens if someone stops the medication. Current evidence suggests that, like other GLP-1-based drugs, stopping retatrutide leads to weight regain, meaning it's likely a lifelong treatment.

The Science Behind the Success​

Why Three Hormones Are Better Than One​

Each component of retatrutide contributes uniquely:

GLP-1 primarily reduces appetite and food intake—it's the "eat less" signal. It also improves blood sugar control and may have cardiovascular benefits.

GIP enhances the effects of GLP-1, particularly on insulin secretion and glucose metabolism. Interestingly, while GIP can promote fat storage in normal conditions, when combined with GLP-1 in the context of weight loss, it appears to enhance fat breakdown and improve body composition.

Glucagon is the "burn more" signal. It increases metabolic rate, promotes fat breakdown, and enhances energy expenditure. This is particularly important because as people lose weight, their metabolism typically slows down—a phenomenon called "metabolic adaptation" that makes further weight loss difficult. Glucagon's metabolic boost helps counteract this.

The Synergistic Effect​

The real magic happens when these three pathways work together. It's not just additive (1+1+1=3), but synergistic—the combined effect appears greater than the sum of the individual parts. This is why retatrutide's weight loss exceeds what we might predict by simply adding the effects of its individual components.

Real-World Implications​

For Patients​

Retatrutide offers hope for people who have struggled with obesity for years, trying countless diets, exercise programs, and medications with limited success. The magnitude of weight loss—approaching surgical results—could transform lives, potentially reversing type 2 diabetes, reducing cardiovascular risk, improving mobility and joint health, and enhancing quality of life.

For Healthcare Systems​

Obesity costs healthcare systems hundreds of billions of dollars annually through direct medical costs and lost productivity. A medication that can produce 24% weight loss could significantly reduce obesity-related complications like diabetes, heart disease, and orthopedic problems, potentially saving healthcare dollars long-term.

However, these medications are expensive—often $1,000-1,500 per month without insurance coverage. The cost-effectiveness equation depends on:

Long-term health improvements and complication prevention

Insurance coverage and pricing negotiations

Whether patients need to stay on the medication indefinitely

For the Obesity Treatment Landscape​

Retatrutide represents a philosophical shift in how we think about obesity treatment. It reinforces that obesity is a chronic disease requiring ongoing medical management, not a personal failure requiring more willpower. Just as we treat diabetes, hypertension, and high cholesterol with long-term medications, obesity increasingly requires pharmacological management.

What We Still Need to Learn​

While the results are exciting, retatrutide is still in Phase 3 clinical trials. Important questions remain:

Long-Term Safety​

The current data extends to 48 weeks, but we need years of follow-up to understand:

Long-term safety profile

Cardiovascular outcomes (ongoing CVOT trials will answer this)

Effects on bone health with sustained weight loss

Cancer risk (if any) with prolonged exposure

Impact on mental health and quality of life

Durability of Weight Loss​

Can people maintain the weight loss for years?

What happens if they stop the medication?

Will the body develop tolerance over time?

What's the optimal long-term dosing strategy?

Real-World Effectiveness​

Clinical trials involve highly selected, motivated participants with regular support. Real-world results may differ due to:

Lower adherence to weekly injections

Less intensive lifestyle support

More diverse patient populations

Insurance coverage and access issues

Special Populations​

More data is needed for:

Adolescents and young adults

Older adults (>65 years)

Different ethnic groups

People with specific comorbidities

Combination with other treatments

The Road to FDA Approval​

Retatrutide is currently being developed by Eli Lilly under the brand name investigational status. The company is conducting multiple Phase 3 trials:

TRIUMPH Program: A series of large clinical trials examining retatrutide for:

Obesity management

Type 2 diabetes

Obstructive sleep apnea

Heart failure with preserved ejection fraction

Metabolic dysfunction-associated steatohepatitis (fatty liver disease)

If the Phase 3 trials confirm the Phase 2 results, FDA approval could come as early as 2025-2026. However, approval doesn't guarantee access—insurance coverage, manufacturing capacity, and pricing will all affect real-world availability.

Practical Considerations​

Cost and Access​

Based on similar medications, retatrutide will likely cost $1,000-1,500 monthly without insurance. Coverage will depend on:

Insurance plan formularies

Prior authorization requirements

BMI thresholds and comorbidity requirements

Step therapy requirements (trying other treatments first)

Lifestyle Still Matters​

Retatrutide is not a magic bullet that eliminates the need for healthy behaviors. The best results come from combining medication with:

Nutrition: While appetite suppression makes eating less easier, food quality still matters. Adequate protein intake is crucial to preserve muscle mass during weight loss. A balanced diet ensures proper nutrition despite reduced calorie intake.

Physical Activity: Exercise helps preserve muscle mass, improves cardiovascular fitness, enhances mood, and may improve long-term weight maintenance. Resistance training is particularly important during weight loss.

Behavioral Support: Addressing emotional eating, developing sustainable habits, and having support systems improves long-term success.

Medical Monitoring: Regular follow-up to monitor weight, metabolic markers, and potential side effects is essential.

The Bigger Picture​

Retatrutide is part of a revolution in obesity pharmacotherapy. We've moved from medications that produced modest weight loss with significant side effects to highly effective therapies that rival surgical interventions. This progress reflects deeper understanding of:

Obesity Biology: Recognition that obesity involves complex hormonal, neurological, and metabolic dysregulation—not simply willpower failure.

Gut Hormone Systems: Understanding how hormones like GLP-1, GIP, and glucagon regulate appetite, metabolism, and energy balance.

Drug Design: Ability to create molecules that precisely target multiple receptors simultaneously with optimal pharmacokinetics.

Beyond Weight Loss​

The metabolic improvements with retatrutide extend far beyond the number on the scale. The medication appears to improve:

Insulin sensitivity and diabetes control

Cardiovascular risk factors

Liver health

Inflammatory markers

Physical function and quality of life

This holistic improvement in metabolic health is what truly makes retatrutide potentially game-changing.

Looking Forward​

The obesity treatment landscape will continue evolving. Future directions include:

Combination Therapies: Pairing retatrutide with other medications targeting different pathways—perhaps muscle-building agents to optimize body composition, or medications addressing specific obesity-related complications.

Personalized Medicine: Identifying which patients respond best to which medications based on genetic profiles, metabolic characteristics, or other biomarkers.

Improved Formulations: Monthly or even longer-acting versions, oral formulations, or combination products.

Broader Indications: Using these medications for obesity-related conditions beyond weight loss, such as fatty liver disease, sleep apnea, or joint disease.

Conclusion​

Retatrutide represents a quantum leap forward in obesity pharmacotherapy. Its ability to produce 24% average weight loss—approaching surgical results through a once-weekly injection—is unprecedented for medication therapy. The triple agonist mechanism addresses multiple aspects of metabolic dysfunction simultaneously, producing not just weight loss but comprehensive metabolic improvement.

However, we must maintain perspective. Retatrutide is still investigational, requiring more data on long-term safety, durability, and real-world effectiveness. It will likely be expensive and require lifelong treatment. It's not without side effects, and it won't work equally well for everyone.

Most importantly, while retatrutide is extraordinarily powerful, it works best as part of comprehensive care that includes nutrition, physical activity, behavioral support, and medical monitoring. Obesity is a chronic disease, and retatrutide is a powerful new tool—but tools work best in the hands of skilled practitioners and motivated patients working together toward better health.

For people who have struggled with obesity and its complications for years, retatrutide offers genuine hope. As we await final FDA approval and long-term data, it stands as testament to how far obesity medicine has progressed and hints at even more effective treatments on the horizon.

References​

Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972

Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018;18:3-14. doi:10.1016/j.molmet.2018.09.009

Patel VJ, Joharapurkar AA, Jain MR, Patel PR. Retatrutide: A promising triple agonist for obesity and type 2 diabetes. Drugs Today (Barc). 2023;59(10):515-524. doi:10.1358/dot.2023.59.10.3627764

Thomas MK, Nikooienejad A, Bray R, et al. Dual GIP and GLP-1 receptor agonist tirzepatide improves beta-cell function and insulin sensitivity in type 2 diabetes. J Clin Endocrinol Metab. 2021;106(2):388-396. doi:10.1210/clinem/dgaa863

Wilding JPH, Batterham RL, Calanna S, et al. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038

Müller TD, Finan B, Bloom SR, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019;30:72-130. doi:10.1016/j.molmet.2019.09.010

Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes - state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102

Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placebo on weight loss maintenance in adults with overweight or obesity: The STEP 4 randomized clinical trial. JAMA. 2021;325(14):1414-1425. doi:10.1001/jama.2021.3224

Garvey WT, Mechanick JI, Brett EM, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(Suppl 3):1-203. doi:10.4158/EP161365.GL

Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385(6):503-515. doi:10.1056/NEJMoa2107519

Day JW, Ottaway N, Patterson JT, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009;5(10):749-757. doi:10.1038/nchembio.209

Ambery P, Parker VE, Stumvoll M, et al. MEDI0382, a GLP-1 and glucagon receptor dual agonist, in obese or overweight patients with type 2 diabetes: a randomised, controlled, double-blind, ascending dose and phase 2a study. Lancet. 2018;391(10140):2607-2618. doi:10.1016/S0140-6736(18)30726-8

Eli Lilly and Company. A Study of Retatrutide (LY3437943) in Participants With Obesity or Overweight (TRIUMPH-1). ClinicalTrials.gov identifier: NCT05929326. Updated November 2023.

Blonde L, Umpierrez GE, Reddy SS, et al. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan—2022 Update. Endocr Pract. 2022;28(10):923-1049. doi:10.1016/j.eprac.2022.08.002

 

[USMC]

tldr; absolutely the best weight loss peptide IMHO to date

I want to summarize my early exp. with retatrutide. I could not handle any semaglutide in the past, even 0.1mg gave me hellish nausea and lethargy. but R. is different.
- 2 weeks ago I started a protocol, 2mg/week, divided in 2 injections.
- absolutely no nausea or lethargy, if anything a good energy boost
- significant appetite reduction, but you can still eat, to give you an example, my typical lunch would be normally 400g ground beef, i can do 150g and can pretty full.
- a bit harder to hit protein levels
- diet shifted more towards carbs then fat (hard time eating a lot of meat)
- body burns very fast through carbs. had to shift diet towards rice/potatoes/meat+some fruit

downsides:
- sugar cravings can be real, and I did exp. some hypoglycemia (55 blood glucose) after gym workouts. managing diet is a bit more tricky, if you workout a lot (me), but it does not cause you energy to dive whatsoever.

Is this something you get via script, or a peptide source? I had great results the 1st time I tried Saxenda.. I tried it again several months later and nothing! Strange.. I've tried the peptide source of Semaglutide and again nothing.. I would love to try something like Retatrutide to see if it works.. Either way, glad it is working for you

 

[t_spacemonkey]

Is this something you get via script, or a peptide source? I had great results the 1st time I tried Saxenda.. I tried it again several months later and nothing! Strange.. I've tried the peptide source of Semaglutide and again nothing.. I would love to try something like Retatrutide to see if it works.. Either way, glad it is working for you

peptide sources. i can give you list via DM or find your own. i found a source 40usd/10mg. have not tried yet waiting on delivery. the one now i paid 120usd/10MG

 

[USMC]

peptide sources. i can give you list via DM or find your own. i found a source 40usd/10mg. have not tried yet waiting on delivery. the one now i paid 120usd/10MG

Sure, could you DM me when you get a second? Would appreciate that, thanks!

 

[USMC]

Thanks, I'll check them out.. is this stuff FDA approved yet? Not that that will stop me just curious..

 

[t_spacemonkey]

Thanks, I'll check them out.. is this stuff FDA approved yet? Not that that will stop me just curious..

good one. side note I found it curious that they are able to synthesize it when its not even released and not past early trials.

 

[belttom]

good one. side note I found it curious that they are able to synthesize it when its not even released and not past early trials.

Can you dm me the source?

 

[t_spacemonkey]

its been a while. so wife, 6 months in, 2x3mg/week, lost 50lb (while watching diet + training).
personally I eventually stopped, because of persistent insomnia. I am retrying at something like 2x300mcg to see if my body eventually adjusts, but this compound might not be for me. i found a solid source for something like 25usd/10mg, which is the cheapest US i've seen.

 

[Shickster1]

peptide sources. i can give you list via DM or find your own. i found a source 40usd/10mg. have not tried yet waiting on delivery. the one now i paid 120usd/10MG

Me too please!

 

[Fxxx]

its been a while. so wife, 6 months in, 2x3mg/week, lost 50lb (while watching diet + training).
personally I eventually stopped, because of persistent insomnia. I am retrying at something like 2x300mcg to see if my body eventually adjusts, but this compound might not be for me. i found a solid source for something like 25usd/10mg, which is the cheapest US i've seen.

Would you possibly mind sharing that source ?

 

[Fxxx]

its been a while. so wife, 6 months in, 2x3mg/week, lost 50lb (while watching diet + training).
personally I eventually stopped, because of persistent insomnia. I am retrying at something like 2x300mcg to see if my body eventually adjusts, but this compound might not be for me. i found a solid source for something like 25usd/10mg, which is the cheapest US i've seen.

Would you mind sharing that source?

 

[t_spacemonkey]

got another order in. latest pricing from my UGL source is 450usd for 10*30mg vials. this is about a year+ supply for most people. back on it. i hated tirzepatide. don't want to disclose sources here, but you will be able to dig yourself to it by going on SST(steroidsourcetalk)

 

[om777]

got another order in. latest pricing from my UGL source is 450usd for 10*30mg vials. this is about a year+ supply for most people. back on it. i hated tirzepatide. don't want to disclose sources here, but you will be able to dig yourself to it by going on SST(steroidsourcetalk)

@t_spacemonkey Out of curiosity why did you hate tirzepatide?

 

[t_spacemonkey]

@t_spacemonkey Out of curiosity why did you hate tirzepatide?

it did not suppress appetite till about 7mg or so, but at that level my healthy cravings (meat/dairy etc) turned into sugar cravings. so i could not touch any of the good food, thinking about a steak made me nauseas, but sugar unlimited. I am permanently done with all glp's

 

[Nelson Vergel]

More information: Retatrutide - A Game Changer in Obesity Pharmacotherapy - Page 2 - Excel Male Health Forum

 

[Nelson Vergel]

Protocol details from a member: Retatrutide noob questions (order already done) - Excel Male Health Forum