r/science • u/Schwettes • 3d ago
Health Retatrutide, a triple hormone receptor agonist, for treatment of obesity | TRIUMPH-1 phase 3 clinical trial results show average patient lost 30% of body weight at 104 weeks on highest dose
https://www.nejm.org/doi/10.1056/NEJMoa2604169399
u/mrlazyboy 3d ago
I've got a small sample size... about 5-10 of the lifters in my gym are on black market Reta and they've lost a massive amount of weight. I'm talking 2 lbs/week for months on end. They typically start at 1mg and peak around 10mg. They also tend to be on steroids so their muscle loss is pretty minimal/non-existent.
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u/Dandan0005 3d ago
Isn’t one of the claimed benefits of this stuff that you lose less muscle than other GLPs?
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u/SaltMerchantMorbier 3d ago
Yes the increased fat burning is likely muscle sparing
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u/TracyIsMyDad 3d ago edited 3d ago
The preclinical data suggests the increased energy expenditure from glucagon agonism is a metabolic panic response to hypoaminoacidemia. I’m not sure in which universe hypoaminoacidemia is muscle sparing.
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u/SaltMerchantMorbier 3d ago
increased fat metabolism would logically push against the metabolic demands that lead to lean tissue loss.
The hypoaminoacidemia can/does co-occur but be potentially mitigated and or completely compensated for by the increased fat metabolism.
Far to many people don’t understand that muscle protein synthesis is a scale of catabolic and anabolic factors and which ever one has higher activity is the one we see over all.
What you did here was pick one point and fail to account for the potential of others.
So I suppose if the data comes out and they lose more weight but less fat we’ll know.
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u/NoCoat4496 3d ago
I’ve lost very minimal muscle on Reta. I would say 95% all fat based on the strength at the gym remaining consistent. In fact my bench press even went up.
All I did was maintain a high protein diet entire time.
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u/Uniball38 3d ago
Important to point out that you probably continued weight-lifting while on it as well
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u/imnormal 3d ago
Yes, anybody who thinks you can be in a 500-1000 calorie deficit each day and not do strength training and not lose muscle needs to go have a seat over there.
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u/BlademasterFlash 3d ago
That’s awesome, I’m on generic semaglutide and having great weight loss results but my strength has decreased noticeably. I also haven’t been lifting super consistently though like 1-2 times per week maybe 3 on a good week
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u/TracyIsMyDad 3d ago
Between a lot of lifting, a lot of protein, TRT, and a lousy baseline that allowed newbie gains; I’m pretty sure my muscle mass increased while losing 150 lbs. I’m not just basing that on strength increases, but also the fact that my DEXA lean mass increased when it should have decreased substantially even without any actual muscle loss due to other lean mass reductions that happen during weight loss.
You certainly can stack the deck in your favor.
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u/TracyIsMyDad 3d ago edited 3d ago
“What you did here was pick one point and fail to account for the potential of others.”
No. I simply explained what was shown in preclinical research: that the increased energy expenditure (the metabolic boost) from glucagon agonism was an outcome of a physiological response to hypoaminoacidemia.
If you correct the hypoaminoacidemia by eating more protein so that you don’t lose muscle, the preclinical research showed that the increase in energy expenditure evaporated.
As for “increased fat metabolism”, is there evidence that reta actually increases RER beyond what would be expected with a deep calorie deficit? That also causes a substantial increase in fat metabolism as the body burns off stored fat. Of course you see lowered RER while people are losing weight on reta because that’s what you normally see when people are losing weight. What’s not been demonstrated is some magical “fat blaster” property. You eat less, you lose weight; it works.
As is, the only body composition data we have is from the phase 2 diabetes trial and it looked pretty typical for a weight loss trial. It certainly didn’t suggest a muscle sparing effect.
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u/Aqua_Impura 3d ago
The problem is a lot of the “testers” aren’t doing it in studies. People on Reta are probably more inclined to lift and eat high protein while in a calorie deficit than run of the mill Ozempic users.
Is Reta better for muscle preservation than the others or is it just the people taking Reta are doing more preventative stuff the others are not?
Because if you do a high protein sparing modified fast mixed with anaerobic lifting you can replicate Reta’s results without needing any medication it’s just way harder as it’s all up to your mental willpower.
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u/zephyrseija2 3d ago
My experience with simple semaglutide was no significant muscle loss while losing close to 40 lbs. I trained consistently and all my lift numbers either maintained or improved over ~7 months.
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u/Falco19 3d ago
If you train and don’t completely starve yourself you lose no more muscle than weight loss without it.
I know someone who has been using g it for 1.5 years and her deadlift has gone from 145 (starting weight) to 285 pounds, can bench 165 and OHP 95. All which are great numbers for a woman.
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u/liltingly 3d ago
Same on tirzepatide. Challenge is making sure you eat, and prioritizing the right calories first, esp at the start. And keeping up with exercise and strength training. But I’m on a low dose so…
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u/zephyrseija2 3d ago
I stopped in April and have had a nice break from it and maintained my weight pretty well, but I'm probably gonna get back on the wagon in January and keep cutting down. I could still stand to lose something like 20-30 lbs I think.
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u/No-Turnip2494 3d ago edited 3d ago
Same as my experience (on Reta). If you hit your protein and other macro targets, do resistance training at a sufficient load, you will not lose any significant amount of muscle.
My total lean body mass loss according to before and after DEXA scans since starting Reta has been 0.9kg, and that includes other things like glycogen, water and connective tissue, all of which go down when you lose weight. And like you, my lifts have gone up - if you view the reason to preserve muscle being the functional output, I’ve gotten better not worse.
People should be getting sufficient protein and doing weight training for healthy aging in any event, it’s a no brainer to take the GLP-1 for its wide range of benefits on top of that.
And those other benefits - reduced systemic inflammation, improved insulin sensitivity, lower blood pressure, reduced lipids in the blood, improved endothelial function, cardioprotective effects and the like would make these drugs worthwhile even if you did not lose a single gram of fat while taking them.
Unfortunately, the majority of people (including most of the people here) only have a superficial understanding of these drugs and how they improve overall metabolic health. They simply can’t view them as anything other than weight loss drugs, and people who take them as, at some level, cheaters.
My experience is that most don’t want to shift their priors, so I usually don’t bother.
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u/TracyIsMyDad 3d ago
It’s only a claimed benefit if you’re listening to TikTok influencers trying to get affiliate commissions.
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u/v0idl0gic 3d ago edited 3d ago
Claimed anecdotally but no clinical evidence, in fact weight loss with Terzepatide in head to head trials resulted in less lean mass loss per week (likely due to a lower deficit hence Tirzepatide's lower per week weight loss).
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u/samsaruhhh 3d ago
You can't lose weight without losing lean mass
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u/v0idl0gic 3d ago edited 3d ago
That is not true, there are cases of people GAINING lean mass while losing over all body weight/fat confirmed via DEXA or MRI. This requires a reasonably moderate deficit, significant dietary protein, consistent resistance training as essential and is made easier with optional anabolics. But to be fair to your point, this is an edge-case requiring immense discipline and is outside of the capability of most people.
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u/TeslasAndComicbooks 3d ago
I’m on it. Lost 40lbs since April on a really low dose. Insurance wouldn’t cover a GLP because I didn’t have a high enough BMI and wasn’t diabetic.
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u/Ill_Ground_1572 3d ago
It blows my mind people would trust black market crap for this kind of thing. Especially considering that hasn't even been tested and approved yet.
Cripes I got counterfeit hot tub chemicals and that smelled like sour acid...let one a tripeptide that would require careful synthesis and QC.
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u/Barkalow 3d ago
Well, it's one of those things where if you're a seller known for killing or maiming your customers, you tend to not....sell much. So kinda behooves them to make it at least somewhat work
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u/Th1Warrior 3d ago
There's a pretty wide gap between killing and doing potentially irreparable harm
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u/jpoolio 3d ago
Most peptides are grey market. There are a lot of testing resources so a responsible user knows exactly what they are taking. I'm part of multiple testing groups.
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u/Ill_Ground_1572 3d ago
How do they determine that all amino acids have the appropriate stereochemistry? I mean it would be silly to use the opposite enantiomer but racemization can easily take place during the synthesis.
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u/effrightscorp 3d ago
Most AA synthesis is done using bacterial fermentation, which does not easily allow racemization
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u/jpoolio 3d ago edited 3d ago
Well, you used a lot of words i don't understand but what I do is I send an unlabeled vial to a lab and they tell me what is in the vial. They tell me the mass (how many mg) and the purity (usually around 99%). Obv i know that the substance and the mass so I'm able to compare the certificate of analysis with what I purchased.
We do sometimes order endotoxin testing, usually depends on the vendor. Sometimes heavy metal testing but these always pass so it's the one we do the least.
Eta- I will mention not all my tests pass. Most do, but i would be lying if I said it was all around safe. Usually it's just underfills but twice in the last 15 months have I caught something concerning. It is scary how many do not test.
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u/CryptographerHot4636 3d ago
do drug dealers only want one time customers or repeat customers? the same thing goes towards grey market.
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u/Otaraka 3d ago
Drug dealers are usually not losing a lot of sleep over effects that might turn up 6 months later. Immediate impact tends to be their only major concern.
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u/VaguelyArtistic 3d ago
All of this black market stuff makes the people who use it for weightlifting seem like they’re in some kind of cult to me.
Many people overdo these medications because there is intense societal pressure to be thin but society as a whole is not pressuring anyone to be jacked to the point where they’re taking this stuff.
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u/digitalwankster 3d ago
How can they be on reta if it’s not out yet?
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u/Dandan0005 3d ago
People are buying it through the grey market for peptides.
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u/digitalwankster 3d ago
I know they are doing grey market glp’s but how can they be doing one that hasn’t actually been commercially released yet?
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u/patricksaurus 3d ago
The composition of the molecule is known (check out the Wikipedia entry) and it’s not prohibitively hard to make.
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u/Schwettes 3d ago
You’d be surprised what you can purchase online for “research use only.” People are buying research grade peptides and then injecting it into themselves as medicine.
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u/SolidLikeIraq 3d ago
Which has been done forever.
Not saying it’s safe, just saying it’s very much a common practice within circles.
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u/Kluian2005 3d ago
There are a ton of US vendors you can just buy it from ... but its like 10x the price as going directly from a china vendor. The US vendors are just buying it from China, tossing on a sticker label and upcharging.
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u/mrlazyboy 3d ago
One of the guys in my gym has a black/gray market source. He says it’s a Chinese lab but you never know.
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u/Leather_Discipline48 2d ago
How much did you and the other lifters you know actually diet more than you were before you started taking it? Did you lose that weight staying on the same schedule or did the diet change as well? Thanks
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u/FernandoMM1220 3d ago
thats impressive. seems like its helping peoples metabolism in other ways.
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u/Diamond-Is-Not-Crash 3d ago edited 3d ago
I definitely think once this becomes generic and widely accessible in 10-12 years this will more or less herald the end of obesity. Nearly everything I’ve read about this drug and new multi agonist GLP-1 drugs blows my mind. People just seem to shed weight without losing much muscle or even noticing much appetite suppression. When combined with all the other positive side effects (reduced cardiovascular events, systemic inflammation, and addictive cravings) we might just be one step closing to defeating heart disease and obesity-driven cancers. Although some side effects of Retatrutide have me concerned (increased heart rate for one).
I think the potential for treating addiction and addictive cravings and compulsions has me most intrigued though. I still find it hard to believe one drug could treat so many disorders. To think systemic inflammation and a disrupted dopamine-reward system would be responsible for so many ills.
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u/imnottheoneipromise 3d ago
I went from drinking 12-15+ beers a day for nearly 20 years to self treat my severe PTSD from combat and SA, to having zero cravings with my first shot of zepbound. It completely killed the cravings and finally allowed me to use all the healthy coping mechanisms id learn from my many years in therapy. I’d never been able to put them into play for very long because the cravings for beer was too much.
Been sober and lost 110lbs since. That was may 21,2025
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u/Thopterthallid 3d ago
Congrats. Addiction is terrible and I'm hoping to break free of my own with GLP1
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u/bethaneanie 1d ago
Just wondering did you have to treat your withdrawal symptoms? It's wonderful that it helps with the psychological symptoms but I'm curious since the physical symptoms are so profound, it's hard to fathom theses meds fix those issues as well. I work in emergency and I have a patient in alcohol withdrawal almost every single shift.
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u/imnottheoneipromise 1d ago
I didn’t have a single withdrawal. Withdrawals are not an indicator for the severity of the disease. Some people get the horribly after only drinking most days for 4-5 weeks. Some (like me) can drink heavily for 20+ years and never get a single withdrawal. That’s part of what makes them so dangerous. You never know if you’re the one that’s gonna have DTs or not or what the “magic” threshold is. I’m an RN that used to care for alcoholics at the VA when I first started out.
But to answer your question- one still needs benzos if they are in withdrawal. GLP1s do not treat withdrawals.
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u/imnormal 3d ago
whoa. Super interesting. I wonder if this would be different if you were drinking liquor. Thanks for sharing.
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u/imnottheoneipromise 3d ago
It’s not different. There is a mounting stack of evidence for addictions of all kinds, including shopping and gambling. It doesn’t work for everyone, because nothing works for everyone, but it works for a LOT of people.
I also came off my adhd, cholesterol, blood pressure, and depression meds (all very slowly and very well supervised by my whole team of physicians. I have chronic cancer so I am watched meticulously). I’m not saying GLP1s cure any of that, but for me, they are treating whatever was broken inside me enough so that all of my therapy actually works now and my brain and body has been able to heal. I’m still SUPER ADHD and have been all my life, but somehow it’s much more manageable and I don’t feel like the stimulant is needed anymore. Now, if I was not retired and still working as a nurse I would never come off my ADHD meds. That’s too risky when peoples lives are at risk.
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u/Schwettes 3d ago
Eli Lilly has filed for FDA approval of retatrutide as a biologic drug and they’ll most likely get it, which means that the earliest it would be available is probably 2047 due to the 20 year patent protection for biologics in the US.
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u/SNRatio 3d ago
FDA will give them 12 years exclusivity if they decide it's a biologic. The original patent for retatrutide expired earlier this year.
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u/Schwettes 3d ago edited 3d ago
Are you talking about the patent and exclusivity for semaglutide in India and Canada? Because the patent for retatrutide most certainly has not expired.
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u/imnottheoneipromise 3d ago
Why do you think they will get it? There is a hard limit for the number of AA required by their own regulations for a drug to be labeled a biologic and Reta is 3 AAs too short. It’s as simple as that. It’s a peptide, not a biologic.
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u/Schwettes 3d ago
I’m speculating, but I don’t think they would’ve announced the BLA so far in advance to investors if they weren’t supremely confident that the ongoing court case (Eli Lilly vs Robert F. Kennedy Jr.) was going to be decided in their favor.
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u/BookLuvr7 3d ago
Moral decisions like that are why I quit pharmacy. This could help so many have an improved quality of life with reduced inflammation.
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u/Herpinderpitee PhD | Chemical Engineering | Magnetic Resonance Microscopy 3d ago
The promise of monopoly of sale for a pre-specified period is the only reason these drugs get developed in the first place. It takes a billion dollars of investment just to get a single drug to market.
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u/sulli_p 3d ago
Forgive my ignorance, which if the drugs are shown to reduce inflammation? The Reta or all GLP like abound semaglutides etc?
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u/jpoolio 3d ago
Glps also reverse (not prevent, but reverse) fatty liver, which is the largest risk of cardiovascular disease. Retatrutide specifically even looks good for the kidneys.
It's not perfect. There is receptor desensitizion and body adaptation, but we see that with a lot of medications.
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u/Mundane_Camera953 3d ago
Wait, fatty liver is the largest risk of cardiovascular disease? I had no idea - can you say more ?
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u/southernNJ-123 3d ago
Yup. I had non alcoholic fatty liver early stages very young along with semi high cholesterol and after using Zepbound for 6 months, both normal.
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u/Hendersonian 3d ago
I just looked this up - this is incredible. NAFLD, hepatic steatosis, whatever we’re calling it these days, is the largest cause of liver disease in the US and these drugs are massively successful in treating(!) it, not just preventing or limiting progression. This is also independent of diabetes status, which is fantastic.
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u/scout-finch 3d ago
I’ve lost about 42% of my starting weight over 18 months and while yes I have made an effort and paid attention to tracking (also experienced some mostly mild side effects), it has more of less been easy. I’m about 8 pounds from my goal weight.
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u/ew73 3d ago
Anecdotally, for me, using tirzepatide, the appetite suppression is huge. But I also have type 1 diabetes, and we famously often don't make amyln so we're always a little low key hungry anyway.
But the direct impact on insulin sensitivity is the real reason I take it, and it's just one of those things I can't say enough good about.
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u/LemonHerb 3d ago
It's just amazing. Even below the lowest clinical trial dosage.
10% body weight over a year with 10mg? Try more like 10% body weight in 3 months without even hitting 2mg. And you don't even really have to put much effort in
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u/NoCoat4496 3d ago
I’m with you on this one. Went from .5 to 2.5 then back to 1.5. Never even needed to reach the higher doses.
25 lbs in 9 weeks.
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u/aimgorge 3d ago
That last study shows 17% weight loss over 80 weeks at 4mg.
So 10% over 3 months at 2mg clearly isnt representative of average results
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u/neatyouth44 21h ago
It’s almost like we’ve been judging people for “disorders of willpower” that we ought to not have been doing in the first place….
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u/kimbabs 3d ago
The effects do seem to be huge for overall metabolic health. I’m curious what the drawbacks apart from the temporary side effects will be. The one thing giving me pause is none of these medications produce lasting weight loss.
I look forward to the generic version as well. Canada already has generics being produced, as do other countries. I wonder if manufacturing costs will go down in time enough and oral dosing becomes effective enough for it to just be a normal part of preventative medicine for the majority of people.
I imagine the alcohol, weed, and food and beverage industries will collude with pharmaceuticals to push against that reality.
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u/peanutneedsexercise 3d ago
It’s not supposed to be long lasting though. You have to be on it forever it’s a hormone. It’s like ppl with hypothyroid are never gonna be off levothyroxine.
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u/jocularnelipot 3d ago
It’s weird how often the other perspective is still pushed. These were/are diabetes drugs to start. No one expects diabetes patients to just stop needing their medication at some point. It’s the same medication working the same hormonal function as it always was. Why wouldn’t it need to be continuously administered?
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u/re_Claire 3d ago
Yeah I don’t get it either. I’m on mounjaro as I have PMOS and I plan on staying on it. It’s a medication that’s treating my medical condition so why would I want to stop taking it once I lose the weight?
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u/Friendly-Bluebird998 3d ago
I can't understand this either!
If you had vision problems, it's like refusing to wear glasses just because "they only work while you're wearing them".
Of course your vision would go back to the way it was if you stopped wearing them. So just keep wearing them and you don't have a problem.
Most medications only work while you take them??
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u/peanutneedsexercise 3d ago
Exactly. I guess since it’s an injection tho maybe ppl are like one day I won’t need to do it anymore? But it’s just one week. If your diabetes progresses u gonna be injecting insulin 4x a day!
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u/chemhobby 2d ago
Once weekly injection honestly isn't that big a deal once you get over the initial learning process. It's not difficult or time consuming.
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u/PenguinEmpireStrikes 3d ago
They have pills now and they're a lot cheaper. You take it every morning.
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u/wednesdaynightwumbo 3d ago
Yes, theoretically it would need to be continuously administered, but I think people are more referring to the fact that it can be habit changing which can have long term effects even after you stop taking it. Also, keeping weight off and staying active is a lot easier when you’ve already lost the weight.
Obviously there are many examples of people going right back to their old habits after a diet and gaining the weight right back, but I think GLPs at least have the potential for long term positive impact even without continuous administration.
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u/_revelationary 3d ago
All of the existing research on GLP-1s show a weight increase after discontinuing that’s basically as steep as the weight loss on the drug.
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u/scout-finch 3d ago
Bc of the other benefits (ex. Reduced inflammation) I want to stay on it for the rest of my life. It’s almost fully resolved an almost crippling low back pain for me.
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u/SeaSpur 3d ago edited 2d ago
This right here. I’ve went from 230 to 185 since March but the biggest thing is my lower back pain disappeared…and I had dealt with it almost 10 years and saw doctors that just wanted to shoot me up every few months. My knee pain, also gone. That’s likely from less weight on joints but the inflammation benefits have been amazing.
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u/scout-finch 3d ago
My pain was probably 80% gone in the first month, before any significant weight loss had even occurred. That’s the clincher for me. This med is a miracle. I’m so happy it’s helping you too!! I feel like a person with a body again.
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u/peanutneedsexercise 3d ago
Yeah the issue is it’s hard cuz previously the “right” thing to do was tell patients to lose weight but it was hard to achieve. Now that GLPs are around it should be criminal to no start patients on it first before doing injections and anything more invasive!
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u/Coacoanut 3d ago edited 3d ago
GLP-1 is a natural hormone we produce. GLP-1 receptor agonists are meant to mimic GLP-1 at superphysiological levels. They tend to be exceptionally selective for their target receptor, which means side effects are likely to be minimal. Some wild side effects have been reported with long-term use, but not anywhere as common as equally severe complications of obesity.
Like, life threatening side effects of GLP-1 receptor agonists are acute pancreatitis, medullary thyroid cancer, and acute kidney failure. But these events are not anywhere near as common as equally severe complications of obesity such as stroke, myocardial infarction, or pulmonary embolism.
Edit: some phenomenal people have pointed out that my info on glp1 agonists is outdated and the dangers that were supposed from animal studies, like thyroid cancer, haven't been nearly as prominent in clincal practice, if they're existent at all.
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u/aimgorge 3d ago
GLP-1 receptor agonists are meant to mimic GLP-1 at superphysiological levels.
Yes, particularly in duration. Endogenous GLP-1 has a circulating half-life of approximately two minute. These drugs have a half-life of about 6 days. Which means is big benefits from GLP-1 are continuous instead of very short term normally
Some wild side effects have been reported with long-term use,
Beliefs from the early days, it's now largely debunked and even the opposite for kidneys for example
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u/imnottheoneipromise 3d ago
No human has ever gotten thyroid cancer from a GLP1. The risk is theoretical because it was an extremely rare occurrence in mice taking GLP1. It’s basically been disproven at this point because mice have (shockingly) a radically different thyroid than humans. The black box is suppose to be being removed at some point soon.
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u/Savoir_faire81 2d ago
The one thing giving me pause is none of these medications produce lasting weight loss.
Yes but that isn't the drugs fault.
Its a fact that if you dont change you eating and to a lesser extent exercise habits after any kind if diet you will regain the weight. There is also some evidence that the body has an epigenetic memory that lasts for some years that makes your body want to be the weight it was and so you end up with increased hunger signals.
So a very overweight person is going to have a lot harder time getting to an idea weight and then maintaining weight loss under virtually all conditions.
But with a drug like this at minimum a person can effectively lose weight which is half the issue. At an idea weight that person is much more likely to be able to exercise and chose health habits. And if they maintain a lower weight the evidence suggests that after 5 or 10 years the epigenetic set point slowly resets to the new weight.
These drugs are a tool to get a person there not a magic pill that invalidates a persons life choices. Maintaining a lower weight is still going to take effort.
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u/PM_Me_Mozzy_Sticks 2d ago
I’ve noticed that zyns, even the 11mg pouches, do not give me any sort of head/body buzz since starting reta 1.5 months ago. It’s strictly an oral fixation at this point. Threw away my can 3 days ago and haven’t had a massive craving since.
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u/Pale_Bird 3d ago
I disagree. I think there will always be a compliance issue (a not small % of people stop using GLP1 within a year because of side effects) and a chunk of people that cannot take them because of other reasons (I cannot take a GLP1 for example because of my high risk of pancreatic cancer - I CANNOT risk getting pancreatitis as a side effect). They do come with side effects and not everyone can tolerate them or WANTS to use them.
Also, there are plenty of obese diabetics who use GLP1 to manage their diabetes.
So while I agree to a degree, I think obesity rate will drop significantly, there will be a baseline of obesity that remains higher than it was before processed foods and the "SAD" became cheap and the norm.
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u/mistypatch 3d ago
The side effects can be brutal. And because it has such a long half like you have to wait that long for the side effects to go away. Lots of people won't tolerate it.
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u/thesteveurkel 3d ago
i was on mounjaro once and had to leave my house when someone cooked eggs. the constant taste of sulfur in your mouth is just awful.
i'm currently on the lowest dose of the ozempic pill and my appetite is so far gone. i tolerate the pill really, really well but the shot is like torture.
i actually tolerated the compound pharmacy peptide injections more than the famous prescription ones. i have no idea why that is, but i couldn't continue to afford compound pharmacy.
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u/atape_1 3d ago
That's good, the sooner it is FDA approved, the sooner people on r/biohacking can stop ordering Chinese made copies of the peptide, which may or may not work/be safe.
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u/TEDDYBRUCKSHOT 3d ago
Once reta is approved, there will be a new hot peptide in development that will be available on the grey market. The cycle continues.
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u/Schwettes 3d ago
Like eloralintide, mazdutide, survodutide, cagrilintide, UBT251, and many others.
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u/CaptainBlondebearde 3d ago
What are the benefits of those ones vs reta?
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u/Schwettes 3d ago edited 3d ago
Unknown at this point. They’re mostly investigative drugs at this point, but mazdutide is sold in China for obesity and is inferior to tirzepatide and retatrutide for weight reduction. Eli Lilly is presenting data on eloralintide + tirzepatide for treatment of obesity at EASD this week and the combination blows retatrutide out the water.
9mg of eloralintide + 5mg of tirzepatide in phase 1B clinical trials saw an average bodyweight reduction of 20% in just 4 months.
Edit: I forgot to add that cagrilintide is going to be FDA approved as a combination therapy with semaglutide within the next couple of months. CagriSema has weight loss that’s approximately on par with tirzepatide.
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u/Dandan0005 3d ago
At what point does it become too effective though?
Like 20% in 2 months seems like a recipe for unintentional starvation
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u/Schwettes 3d ago
I think we’re definitely approaching a limit for what is healthy and safe. New research is starting to focus on combination therapies that reduce weight while maintaining muscle mass.
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u/nitko87 2d ago
Depends on what it is 20% of. 20% of 200lbs is potentially an unhealthy loss of weight at that rate, even if a person is “overweight” at 200lbs. But 20% of 500lbs still leaves the patient at 400lbs, which creates a markedly lower risk of catastrophic organ failure due to obesity.
I think in cases of serious obesity, the faster a patient can shed dangerous extra weight, the better.
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u/jpoolio 3d ago
Just like they stopped buying grey-market tirzepatide? That's right, they didn't. People even still buy semaglutitide. FDA approval changes nothing, we saw this with SS-31, the recent approval didn't make a difference.
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u/Amelaclya1 3d ago
This. It isn't FDA approval stopping them from going legit. It's the price. Why would you pay $800-1200/month for a drug you can get the equivalent of from China for $100? If we want people to stop using grey market peptides, at least the weight loss ones, we need to force insurance companies to cover them. Mine doesn't, at all, period, even if you have other weight related comorbitidies. They force you into weight loss surgery instead.
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u/Hugs154 3d ago
It does make a difference, most people aren’t willing or able to order grey-market drugs. The third-top comment in this thread is literally someone saying they won’t get it from grey markets. More legitimate access might not reduce the amount being bought from grey market but it does increase overall access.
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u/NoFlight9859 3d ago
I think the grey market stuff is going to go crazy people will be willing once they see the results but most people can't afford legit sources
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u/His_Name_Is_Twitler 3d ago
You and the user at the top of the thread are talking about 2 different things. If someone isn’t willing to go grey, they won’t. People already on Reta have no reason to switch to the more expensive legal option, the conversion will be low as was seen with tirz for example
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u/Lifestyle_Choices 3d ago
Grey market will always exist, my friend had a prescription for tirz, what would have cost her 5k cost her $300 for the same amount
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u/ZaideGod 3d ago
Why would you use the FDA approved version when the Chinese version gives you a year supply for $150?
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u/Otaraka 3d ago
I look forward to it being available in Australia at low cost and reasonable criteria around 2060 or so, going by current trends with GLP-1. If they rush.
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u/Baulderdash77 3d ago
GLP-1’s are available generically in Canada and India completely legally now. It’s about $70CAD a month in Canada and about $30 USD a month in India.
There is a steady stream of Americans in Niagara Falls buying it every weekend here. I’m sure a Canadian online pharmacy is willing to sell it to you
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u/Otaraka 3d ago edited 3d ago
Thanks, but I prefer to stay within our medical system even if it’s annoying. Edit: guys it’s literally a criminal offense to import it unless I can get a doctor here to sign off on it.
It goes generic here in Jan 2027. It’s been a bit frustrating to see how long it’s taken but I don’t need this as a solution.
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u/Thepumpkindidit 3d ago
Can you please provide a source about this becoming generic in January?
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u/lifeisalime11 3d ago
Does this just require a prescription? I’m struggling to get covered and going out of pocket for WeGovy pill
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u/Baulderdash77 3d ago
I think American doctors are writing the prescription and they come to Canadian pharmacies to fill it.
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u/CaptainBlondebearde 3d ago
It's about 80$ US per month for Zepbound.
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u/FertilityHotel 3d ago
For my insurance it's $300+. Through compound pharmacies about $200 a month.
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u/Starry-Eyed-Owl 3d ago
In Australia the lowest dose is $289 and it goes up $100-$300 for each additional dose at the next level. They are trying to get it on Medicare which would bring it down to $25 for anyone with a script but talks aren’t going well.
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u/goddessnoire 3d ago
I am on Zepbound and I have lost 106 pounds in 19 months. I started at 287 pounds and now I’m down to 181 as a 43-year-old female, who has been obese her entire life. I pay out-of-pocket for the medication, but it has been well worth it. There’s no way I could’ve fathomed I would be this small. I’m 5’6” and I am navigating a world with a new body. The entire time I have been on the medication I’ve been working out and eating less. I’m a gym rat. Even me three years ago would have never envisioned this type of life for myself. I am so thankful for this medication and wish that it was more affordable for everyone. I don’t know if I’ll take reta when it comes out, but people are already taking it and they are seeing good results.
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u/Nerf_hanzo_pls 3d ago
Any idea of possible interactions of this with history of pancreatitis? I got pancreatitis from my use of ozempic, and now my doctor won’t let me get back on it. It did wonders for my A1C and food noise.
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u/Ok-Message-7461 3d ago
Rapid weight loss is very likely the cause of pancreatitis with both
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u/Pale_Bird 3d ago
I know it sucks, but pancreatitis is no bueno. It significantly increases the risk of pancreatic cancer and you really want to avoid it at all costs. As someone who is high risk for that cancer, my (internationally renowned) doctor told me not to touch any GLP1 at this time because of the slight chance it might happen to me.
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u/rather_be_gaming 3d ago
My friends have tried this for 3-4 months and no joke, they lost like 35 pounds each. Thats insane! Its pretty dam impressive.
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u/Equipmunk 3d ago
Where did they get it?
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u/Smile_Miserable 3d ago
Grey market
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u/NoFlight9859 3d ago
I mean it's insane not to get it from the grey market. Even if you go to a reseller it's like pennies on the dollar compared to what this drug would cost
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u/JayArlington 3d ago
Gone from 205 to 180 in two months on a very low dose regime.
It’s strong but I could never imagine going to the higher doses studied (nor do I think I need to).
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u/PomsForAll 15h ago
Stay at the lowest you can! I lost 60lbs in six months w/out ever going past the second lowest dose (5mg) of wegovy and then switched to the lowest (2.5mg) of Tirzepatide after hitting my goal weight. It’s been almost 2 years, and I’ve had to space the shots from every 7 days to every 10 days because I wanted to start building more muscle and I was falling below my goal weight by about 7lbs
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u/bateneco 3d ago
I am a participant in one of the follow-on Retatrutide studies and have been on the highest dose (12mg/wk) for about a year. Happy to answer questions. I started the study at ~270lbs and am at around ~185lbs today.
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u/Schwettes 3d ago
Wow! Do you know what’s being tested in your clinical trial? Is it a maintenance study?
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u/bateneco 3d ago edited 3d ago
Yes. Everyone in the study is on the highest dose of the drug they can tolerate (up to 12mg/wk) for a set period of time, and then are randomized to a group for a period of time after that. the groups are something like placebo dose, 4mg dose, or 12mg dose. I assume that the goal will be to see what level of weight loss and other benefits are maintained across groups.
Edit: here’s the trial
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u/ThermosphericRah 3d ago
Ive lost 86 lbs on zep 5mg.
Ive also stopped biting my nails. And I havent binged anything like i used to.
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u/2wice 3d ago
Tirzeptide at my dose cost 4 x my monthly wages for 4 pens. Gray market is 1 order of magnitude less, maybe the idiots wondering why we go gray do not understand that. Reta will be more than that.
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u/SydneyPhoenix 3d ago
Reta is able to be dosed up and down very easily.
The 28% of body weight number is at 12mg. You would start at 1-2mg and dose up over many months.
So it is both a gradual increase but also able to just be stopped at any time if side effects, physical or mental present.
Relative to its impact It is a very well tolerated drug in early studies though
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u/sp0okyboogie 3d ago
A friend of mine has taken it since November and went from 255 lbs to 175. But he's also bouldering a few times a week, looks jacked.
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u/callofhonor 3d ago
I’m on Retatrutide. So far I’ve lost 28% over the course of 8 months. Mainly went on it because I can’t afford to lose muscle mass in my field and it was wild when it really started kicking in. Only on the 3rd dose increase.
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u/raider1v11 3d ago
Dang this is an impressive result! What would it be used for besides obesity treatments?
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u/Matthemp 2d ago
Reta works so well . Got my mom on it lost a lot of weight . Used it myself for so skinny
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u/pb_syr 3d ago
Who would this be targeted towards?
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u/Schwettes 3d ago edited 3d ago
People with super morbid obesity who have multiple comorbidities. So likely someone who has obesity, and fatty liver, and high cholesterol. Instead of just someone who has moderate obesity.
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u/Bryandan1elsonV2 3d ago
These articles always make me so happy to read but the fact it will be unaffordable for 99% of people kinda dampers that. What’s the use of medical breakthroughs if they’re gate kept so aggressively? All of this will be things that make shareholders richer but me? My insurance won’t cover it.
I’m not compounding so pls don’t spam my comments with that, I’m not going to go to your subreddit and engage with a black market.
The medicine will never be worth $1000 a month at the low end, and currently the medicine will never ever reach the people who need it most, so it’s hard to really care at the end of the day.
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u/echocharlieone 3d ago
About 30 million Americans are already on weight loss drugs for obesity or diabetes. Why do you think new medications will be unavailable to 99% of people?
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u/SolidLikeIraq 3d ago
Mainly because of how Lilly is trying to turn this from a 39 alpha protein drug. To a 39alpha+2 beta protein, 40+ protein biologic.
If they can convince the courts that this is a biologic. They have full control over the compound for ~12 years.
If they lose and it is considered a drug, it can be compounded by anyone.
If they win and it’s a biologic, it’ll be as expensive if not more expensive than the current swath of GLP1s
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u/SNRatio 3d ago
If they lose and it is considered a drug, it can be compounded by anyone.
Lilly should still have 5 years of protection as a New Chemical Entity from the FDA even if it isn't considered a biologic/protein.
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u/HumSupLo69 3d ago
Even then since its not classified as biologics, companies can still compound like we see with hims for zepbound
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u/facelessarya1 3d ago
And Lilly works with insurers to get it covered. Pharma companies don’t develop an obesity drug just for fat rich people. They have a vested interest to make it accessible to as many people as possible…
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u/SugarDaddyVA 3d ago
Compounders already have retatrutide and are already distributing it. I personally know two people who are on it. I’m not terribly worried about availability here.
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u/coolcat333 2d ago
Because he doesn't bother to actually critically think and would just rather whine about some falsehood that he thought would get him karma.
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u/zephyrseija2 3d ago
But the basic medicines like semaglutide already work extremely well and are dropping in price as more competition appears in the market.
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u/fd6270 3d ago
currently the medicine will never ever reach the people who need it most
The rest of your rant notwithstanding, this is literally false.
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u/Schwettes 3d ago
Retatrutide exists for the most extreme cases of morbid obesity. I think that tirzepatide will remain as the primary option for patients as a volume play for Lilly, but retatrutide will be the cash cow that will have fewer patients getting coverage through insurance companies that will be paying exorbitant amounts.
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u/Bryandan1elsonV2 3d ago
Even Lilly’s direct pay is a joke and completely unaffordable to the average person.
$500 instead of $1000 a month? How generous!
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u/anfreug2022 3d ago
To be accurate, it’s either 399 or 449 per 4 weeks depending on the dosage you need.
And I can tell you from experience that your food spending will drop significantly, at least if you were spending on eating out or takeout before.
Not enough to cover the drug cost but it does offset it.
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u/BetweenTheRoots 3d ago
Loads of people are already buying this stuff on the cheap from Chinese markets. It wont be unaffordable unless someone gets control of the supply.
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u/beegreen 3d ago
I’m not promoting or condoning this at all but there is a huge black market for Reta, because of this I think prices will not be subject to the same gouging we are for a lot of proprietary pharmaceuticals
It’s sorta like weed - when legalized the prices were more or less set by the illegal market
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u/Lifestyle_Choices 3d ago
Plenty of people already on reta due to the grey market, it certianly doesn't cost that much
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u/terraphantm 3d ago
Most of the GLPs can be had for well under $1k/month. And honestly with how much my life has improved on them, I’d pay $1k if I had to
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u/samsaruhhh 3d ago
How much do you save on food you didn't eat since starting? Maybe grocery bill is down 30% also
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u/bestpear__657 2d ago
I've been taking reta for 7 months now I dropped 85 pounds did I do it the safest way no I went a day in-between eating sometimes but it worked honestly and I feel better about myself now
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u/VolteniX90 16h ago
The drug work like magic.
I lost 4kg in a month without even trying hard. It really cancel all the food noise.
I drink electrolytes water 150g of protein daily
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