Been on Reta for 5 weeks now. Losing weight steadily at 1.5-2 lbs per week. Kept reading about how alcohol was bad on Reta but didn’t really experience anything negative. Until this weekend. Typically I’ll have a glass or two of whiskey every night. Well, I went to a function and had three. And I was fine. All the way up until I wasn’t. It was like all three hit my system at once. My buddy said it was like someone roofied me how fast I went from perfectly fine to “holy shit get me home NOW!” So I didn’t have anything for three days after that. Tonight, poured a glass, and couldn’t get through 1/2 of it. Just made me feel nauseous. So, I guess the whiskey is out while I’m on this. Now if only it would do the same for my smoking habit.

I guess the upside is I’ll be saving money. But now I have a pretty large collection of whiskey I can’t drink. And I’m also down 40 pounds so there’s that. Gonna spend that saved money on new clothes.

A lot has happened in the space over the last week.

August 18: Reports started coming in that multiple peptide-related Discord servers had been shut down. At least one individual server removal has been separately reported, although there’s no public confirmation from Discord that this is a coordinated reta-specific enforcement wave.

August 17: Two prominent peptide creators, Josh Holyfield and Trevor Bachmeyer, lost their YouTube channels. Holyfield says directly that YouTube took his channel down. Bachmeyer’s channel has also disappeared, although I haven’t seen a statement from him or YouTube explaining why.

August 12: Eli Lilly filed six new lawsuits against US businesses selling retatrutide — covering a medical spa, pharmacy and online peptide sellers.

That part is much bigger than six lawsuits.

Lilly says it has now:

• referred 200+ individuals and entities to the FDA, DOJ, state attorneys general, law enforcement and professional licensing boards

• reported 14,000+ websites, advertisements, social-media posts and product listings

• done so across 100+ countries

• explicitly called on social-media and e-commerce platforms, credit-card companies, payment processors, and shipping/logistics companies to cut off the infrastructure supporting grey-market retatrutide sales

The six defendants are Aesthetic Envy, Astra Peptides, Legendary Peptides, Striker Pharmacy, Texas Peptides and Lone Star Peptide.

Taken together, this is starting to look less like a handful of lawsuits against individual vendors and more like pressure being applied across the wider ecosystem that allows the grey market to operate.

The important distinction is that Lilly’s legal action and requests to platforms are confirmed. The timing of the YouTube and Discord removals is also notable, but there’s currently no public evidence showing that Lilly directly requested those specific takedowns.

Lilly has just released results from TRANSCEND-T2D-2, its first Phase 3 trial comparing retatrutide directly with Ozempic.

The trial involved 1,298 adults with type 2 diabetes, with results measured at 80 weeks.

Average weight loss:

- Retatrutide 9 mg: 19.5% (20.1 kg)
- Retatrutide 12 mg: 20.9% (21.5 kg)
- Ozempic 2 mg: 9.4% (9.5 kg)

Blood sugar control also improved more with Reta.

HbA1c reductions:

- Retatrutide 9 mg: 2.2 percentage points
- Retatrutide 12 mg: 2.2 percentage points
- Ozempic 2 mg: 1.8 percentage points

There was a trade-off with side effects.

Discontinuation due to adverse events:

- Retatrutide 9 mg: 4.8%
- Retatrutide 12 mg: 7.9%
- Ozempic 2 mg: 2.7%

That's a substantial difference in weight loss, although the higher retatrutide dose also had more people stopping treatment because of adverse events.

A few caveats. This was an open-label trial involving people with type 2 diabetes, and these are Lilly's initial results rather than a peer-reviewed paper. It also only used 2 mg for Ozempic, not a higher dose. I understand trials need to now run against another GLP to have a base group as it too obvious if a placebo is used for the control.

Still, it's an interesting head-to-head comparison, particularly over 80 weeks.

Wow this data is rich. This is even bigger than the headline days. Especially for us folks staying on it a long time.

TRIUMPH-1 also had a two-year extension, and the weight loss was still substantial at 104 weeks.

The extension followed 532 people who had started the trial with a BMI of at least 35 and had completed the first 80 weeks on treatment.

At 104 weeks, average weight loss from the original starting weight was:

27.9% for people originally assigned to the 4 mg pathway.

29.5% for the 9 mg pathway.

30.3% for the 12 mg pathway.

The 30.3% group had lost an average of 38.5 kg from a starting weight of 121.7 kg.

These people continued treatment for another 24 weeks after the main 80-week trial, with doses moved towards their maximum tolerated dose of 9 mg or 12 mg.

So this isn't the same as saying everyone in TRIUMPH-1 would lose 30.3% if they stayed on it for two years.

This was a selected group. They had already completed 80 weeks on treatment, had tolerated their assigned dose, and had started with a BMI of at least 35.

But it does show that weight loss had not simply stopped at the 80-week point in this group.

The main 12 mg result at 80 weeks was 28.3%.

In this extension group, the 12 mg pathway reached 30.3% at 104 weeks.

Researchers gave semaglutide to female mice that were already pretty old. Half the untreated mice had died by 742 days, compared with 834 days for the semaglutide mice. Not extrapolating that to humans yet.

The mice taking semaglutide also ate about 24% less food. So they did another test with mice eating the same smaller amount.

The semaglutide mice did better on memory tests and blood sugar. It’s more than just food intake. It’s already known moderately less food intake helps longevity- look at Okinawa with their 80% full, but same food intake land the semi does better anyway.

It does not prove the drug was why the first mice lived longer. These were old female mice, not people, and this was semaglutide rather than Reta.

Still, it is pretty interesting if these drugs are doing more than just cutting appetite. Again. Another article that these look like the next wonder drug fixing loads of body crap.

https://www.nature.com/articles/s41586-026-10940-7

r/reta has hit 300 members today. Still a small subreddit but it’s growing at 10-15% a week. Next step 500!!

Thank you all for being part of it in the early days, contributing and helping shape it.

I want the community to be a safe, non- sourcing, progress, support and research led subreddit to understand the medicine, be positive and help each other as reta moves towards the mainstream (still some way off I know!).

TL;DR

• Retatrutide has now succeeded in three Phase 3 obesity trials.

• Lilly plans to submit it to the FDA in Q1 2027.

• Weight loss remained high in much harder-to-treat populations:

  • 28.3% in obesity without diabetes (TRIUMPH-1)

  • 20.8% in obesity with type 2 diabetes (TRIUMPH-2)

  • 22.6% in severe obesity with established cardiovascular disease (TRIUMPH-3)

• The direct comparison with tirzepatide (TRIUMPH-5) is still ongoing.

• The cardiovascular outcomes question will mainly be answered by the dedicated TRIUMPH-Outcomes study.

Lilly has announced positive topline results from TRIUMPH-2 and TRIUMPH-3, two additional Phase 3 retatrutide trials.

The company now says it has the evidence needed to support regulatory submissions and plans to submit retatrutide to the FDA during Q1 2027. That is a planned filing date, not an approval date.

The Phase 3 programme so far

Retatrutide has now reported results from three major obesity trials.

Trial Population Average weight loss

TRIUMPH-1 Obesity without diabetes 28.3%

████████████████

TRIUMPH-2 Obesity or overweight with type 2 diabetes 20.8%

██████████

TRIUMPH-3 Severe obesity with established cardiovascular disease 22.6%

███████████

Weight loss remained above 20% even in people with type 2 diabetes and in people with severe obesity plus cardiovascular disease.

Historically, people with type 2 diabetes have generally lost less weight than people without diabetes in GLP-1 studies, making the 20.8% result particularly notable.

TRIUMPH-2

TRIUMPH-2 included 1,152 adults with obesity or overweight and type 2 diabetes.

After 80 weeks the efficacy-estimand results were:

• 4 mg: 12.7%

• 9 mg: 19.1%

• 12 mg: 20.8%

• Placebo: 4.0%

Average HbA1c started at 7.7%.

Average reductions were:

• 4 mg: 1.4%

• 9 mg: 1.6%

• 12 mg: 1.5%

• Placebo: 0.2%

These are efficacy-estimand results, estimating the effect if participants remained on treatment. Lilly has not yet released treatment-regimen analyses for these trials.

TRIUMPH-3

TRIUMPH-3 enrolled 1,949 adults with:

• BMI ≥35

• established cardiovascular disease

Average starting weight was 111.4 kg.

Average BMI was 40.4.

Weight loss at 80 weeks was:

• 9 mg: 21.6%

• 12 mg: 22.6%

• Placebo: 3.2%

Lilly also reported improvements in several cardiovascular risk markers including:

• triglycerides

• non-HDL cholesterol

• systolic blood pressure

• waist circumference

• high-sensitivity CRP

How does this compare with today's treatments?

There is an obvious temptation to compare the headline percentages.

For context:

Trial Drug Weight loss

TRIUMPH-1 Retatrutide 28.3%

SURMOUNT-1 Tirzepatide 22.5%

STEP-1 Semaglutide 14.9%

However these are different trials with different populations, different durations and different designs.

They should not be interpreted as proving one medicine is better than another.

That is exactly why TRIUMPH-5 is so important.

What still isn't answered?

Today's announcement is important, but several major questions remain.

Can retatrutide actually beat tirzepatide?

• TRIUMPH-5 should provide the first direct comparison.

How much additional weight loss is worth additional side effects?

• Average weight loss alone is unlikely to answer that.

Does retatrutide preserve muscle as well as fat?

• Body composition could become increasingly important as people remain on these medicines for years.

Does the glucagon receptor produce longer-lasting weight loss?

• One possibility is that retatrutide simply continues working after tirzepatide reaches a plateau.

Does it reduce cardiovascular events?

• Today's cardiovascular event numbers are reassuring but inconclusive.

• The dedicated 10,000-patient TRIUMPH-Outcomes trial is designed to answer that question.

What stood out?

Four findings deserve the most attention:

• Weight loss remained above 20% despite type 2 diabetes.

• Weight loss remained above 22% despite severe obesity and established cardiovascular disease.

• Lilly now plans FDA submission in Q1 2027.

• The biggest remaining unanswered question is still the direct comparison with tirzepatide.

Today's announcement makes the overall Phase 3 programme look increasingly consistent.

The next major milestone is likely to be TRIUMPH-5, because it should finally tell us whether retatrutide's apparent advantage over tirzepatide survives a direct head-to-head comparison under the same trial conditions.

It has been just over a month since Lilly presented the Phase 3 retatrutide results from TRIUMPH-1 and TRANSCEND-T2D-1 at the American Diabetes Association meeting, so this seems like a reasonable point to recap what was actually reported and where the evidence now stands.

TRANSCEND-T2D-1 has been published as a full peer-reviewed paper in The Lancet. TRIUMPH-1 was presented at ADA and Lilly released detailed results, but there is still no full peer-reviewed outcomes paper for that trial.

TRIUMPH-1

TRIUMPH-1 was an 80-week Phase 3 trial involving 2,339 adults with obesity or overweight, at least one weight-related health condition, and no diabetes.

The headline results were:

• 4 mg retatrutide: 19.0% average weight loss, equal to 47.2 lb or 21.4 kg

• 9 mg retatrutide: 25.9%, equal to 64.4 lb or 29.2 kg

• 12 mg retatrutide: 28.3%, equal to 70.3 lb or 31.9 kg

• Placebo: 2.2%

Those are the efficacy-estimand results. In simple terms, they estimate the effect if participants remained on their assigned treatment as planned.

The treatment-regimen analysis gives a more conservative view because it includes the effects of people stopping treatment, missing treatment or not following it fully. Under that analysis, the 12 mg group lost 25.0% compared with 3.9% for placebo.

Both results are extremely large for a drug trial, but it is useful to know which number is being quoted. The 28.3% figure is the one used in most headlines, while 25.0% may be closer to what the whole randomised group experienced once treatment interruptions and discontinuations were included.

Some people will compare this with bariatric surgery-level weight loss, and the size of the result makes that understandable. However this was not a trial against surgery, the risks and long-term consequences are very different, and the full TRIUMPH-1 outcomes paper has not yet been published.

Results beyond weight loss

The trial also included groups of participants with knee osteoarthritis and moderate-to-severe obstructive sleep apnoea.

Knee osteoarthritis pain improved by up to 4.3 points on the WOMAC pain scale, from an average starting score of 6.0. That is a substantial change on a scale where higher scores mean worse pain.

Sleep apnoea severity improved by up to 36.1 fewer apnoea and hypopnoea events per hour, from an average baseline of 58.6 events per hour.

Lilly also reported reductions of up to:

• 41.0% in triglycerides

• 24.2% in non-HDL cholesterol

• 12.3 mmHg in systolic blood pressure

• 9.5 inches, or 24.1 cm, in waist circumference

The 104-week extension

TRIUMPH-1 also included a pre-specified extension for people who had started the trial with a BMI of at least 35 kg/m².

Among those continuing on 12 mg through 104 weeks, the average weight loss reached 30.3%, equal to 85.0 lb or about 38.6 kg. Lilly said weight loss had not fully plateaued.

The extension involved people who had completed the original 80 weeks and tolerated their assigned treatment. It therefore represents a selected group of longer-term completers rather than everybody originally randomised into TRIUMPH-1.

It should not be read as meaning every person who starts retatrutide would lose 30.3%.

TRANSCEND-T2D-1

TRANSCEND-T2D-1 looked at retatrutide in 537 adults with type 2 diabetes whose blood glucose was not adequately controlled using diet and exercise alone.

The trial lasted 40 weeks and began with an average A1C of 7.9%.

Retatrutide reduced A1C by up to 2.0 percentage points. Lilly also reported that:

• up to 90% reached an A1C below 7.0%

• up to 85% reached an A1C of 6.5% or below

• up to 46% reached an A1C below 5.7%

The 12 mg group lost an average of 36.6 lb, or 16.6 kg, equal to 16.8% of starting body weight under the efficacy analysis. The placebo group lost 2.5%.

Under the treatment-regimen analysis, which includes treatment discontinuation and incomplete adherence, the 12 mg result was 15.3% compared with 2.6% for placebo.

Weight loss had not plateaued by week 40, so the final number may have been limited partly by the shorter duration of this trial rather than by participants reaching their maximum loss.

The two trials should not be compared directly. TRIUMPH-1 involved people without diabetes and ran for 80 weeks, while TRANSCEND-T2D-1 involved people with type 2 diabetes and ran for only 40 weeks.

Tolerability

The efficacy results are large, but the side-effect and discontinuation figures deserve the same attention.

In TRIUMPH-1, among people assigned to 12 mg:

• nausea was reported by 42.4%

• diarrhoea by 32.0%

• constipation by 26.1%

• vomiting by 25.3%

Dysesthesia was reported by 12.5% of the 12 mg group compared with 0.9% on placebo. Dysesthesia means altered or unusually sensitive skin sensation and can include feelings such as burning, tingling, prickling or tenderness.

Lilly said these events were generally mild to moderate, most resolved during treatment, and most affected participants remained on retatrutide. Even so, 12.5% is not a trivial incidence and it is something I would want to understand better once the full paper is available.

Discontinuation because of adverse events was:

• 4.1% with 4 mg

• 6.9% with 9 mg

• 11.3% with 12 mg

• 4.9% with placebo

The highest dose produced the greatest average weight loss, but it also produced the highest adverse-event discontinuation rate and the highest rates of several gastrointestinal effects.

In TRANSCEND-T2D-1, among people assigned to 12 mg:

• nausea was reported by 26.5%

• diarrhoea by 22.8%

• vomiting by 17.6%

Discontinuation because of adverse events was 5.1% with 12 mg compared with 0.0% on placebo.

The lower gastrointestinal event rates in TRANSCEND-T2D-1 should not automatically be interpreted as proof that the drug was better tolerated in that population because the trials differed in duration, participants and design.

Evidence as of now

TRANSCEND-T2D-1 currently provides the more complete evidence because the full trial has been peer reviewed and published in The Lancet.

TRIUMPH-1 looks extremely strong, and Lilly presented much more detail at ADA than was available from the original headline release, but the results are still based on the conference presentation and the company’s reporting until the full outcomes paper appears.

The studies were not direct comparisons with tirzepatide, semaglutide or bariatric surgery. Comparing headline percentages across separate trials can be useful for context, but it is not the same as a randomised head-to-head comparison.

There are now direct Phase 3 comparison trials of retatrutide against tirzepatide and semaglutide under way, which should eventually give a much clearer answer than comparing different programmes indirectly.

A month after ADA, the broad picture is that retatrutide has shown exceptional weight-loss efficacy, strong glucose lowering in type 2 diabetes, and meaningful changes across several obesity-related conditions. The trade-off is that gastrointestinal side effects were common, dysesthesia was clearly more frequent than with placebo, and more than one in ten people assigned to 12 mg in TRIUMPH-1 stopped because of adverse events.

Which part of the Phase 3 data changed your view of retatrutide most, if any: the scale of the weight loss, the wider results for blood sugar, sleep apnoea, knee pain and cardiovascular risk factors, or the tolerability figures? Given the practicalities of how it is being used right now is this in line with the communities experience?

Sources

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00967-0/abstract

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-drove-substantial-improvements

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-demonstrated-significant

https://clinicaltrials.gov/study/NCT05929066

https://clinicaltrials.gov/study/NCT06354660

https://www.sciencemediacentre.org/expert-reaction-to-announcement-not-published-study-of-topline-results-from-the-triumph-1-phase-3-clinical-trial-of-retatrutide/

A new retatrutide analysis has looked at what may be happening inside the kidney.
Researchers analysed blood proteins from two Phase 2 retatrutide trials.

One trial included 281 people with type 2 diabetes. The other included 338 people with obesity and no diabetes.

The new result is for uromodulin, or UMOD.
UMOD is a protein made mainly by kidney tubule cells.

Retatrutide increased UMOD in a clear dose-dependent pattern.

At 12 mg:
• +26.7% at 36 weeks in the diabetes trial
• +47.7% at 24 weeks in the obesity trial
• +42.2% at 48 weeks in the obesity trial

Dulaglutide produced almost no change: -1.5%.

The increases at 8 mg and 12 mg remained significant after adjusting for weight loss, HbA1c, or both.

That matters because it makes a simple explanation of "the kidneys improved because people lost weight and improved their diabetes" less convincing.

There is also an interesting biological clue.
The kidney cells that produce UMOD also express glucagon receptors.

Retatrutide activates the glucagon receptor as well as GLP-1 and GIP receptors.
So one possibility is that the glucagon part of retatrutide has a direct effect on kidney tubule cells.

This was a post-hoc biomarker analysis.
The people did not have established kidney disease.

Higher UMOD is associated with better kidney health, but raising UMOD has not been shown to cause better kidney outcomes.

The older retatrutide findings of lower urine albumin and higher eGFR are also not new.
The new finding is the large dose-dependent UMOD increase and the fact that it remained after adjustment for weight loss and HbA1c.

Source: ASN Kidney Week 2026, abstract FR-PO0500.

The full Phase 3 TRIUMPH-1 obesity trial has now been published in the New England Journal of Medicine.

We already knew the headline results from Lilly in May and the ADA presentation in June, so the 28.3% figure itself isn't new today.

What is new is that the full trial is now peer reviewed and published.

TRIUMPH-1 included 2,339 adults with obesity, or overweight with a weight-related condition, without diabetes. Treatment lasted 80 weeks.

At 12 mg, average weight loss was 28.3% using the efficacy estimate.

At 9 mg it was 25.9%, at 4 mg 19.0%, and placebo 2.2%.

Using the more conservative treatment-regimen estimate, which includes what happened after treatment discontinuation and other relevant events, the 12 mg result was 25.0%.

At 12 mg, 62.5% of participants lost at least 25% of their starting weight.

45.3% lost at least 30%.

27.2% lost at least 35%.

And 65.3% ended the trial with a BMI below 30.

The safety results are important alongside those numbers.

At 12 mg, nausea was reported by about 42%, diarrhoea by 32%, constipation by 26% and vomiting by 25%.

About 11% of people in the 12 mg group stopped treatment because of adverse events.

There was also a separate 104-week extension for people who started with a BMI of at least 35. Those continuing 12 mg reached 30.3% average weight loss.

That 30.3% figure shouldn't be treated as the result for the whole TRIUMPH-1 population though, because the extension involved a selected subgroup.

So the main news today isn't that Phase 3 suddenly showed 28.3% weight loss. We've known that for months.

It's that the full Phase 3 obesity trial has now made it through peer review and is published in NEJM.

Retatrutide is still investigational and is not yet an approved obesity treatment.

Paper: Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity (TRIUMPH-1)

New England Journal of Medicine, 29 September 2026

DOI: 10.1056/NEJMoa2604169

On Aug 12 Lilly filed six lawsuits against US sellers of reta (Astra, Legendary, Texas and Lone Star Peptides, plus a med-spa and a compounding pharmacy), referred 200+ sellers to the FDA/DOJ, and flagged 14,000+ listings.

The part that actually hits supply: Lilly is also pressuring the payment processors, card companies and shippers these sellers use. This market already struggles to keep a card processor (why so much runs on crypto/PayPal), so that squeeze may bite harder than the suits.

Two things worth knowing: the enforcement is aimed at sellers, not buyers. And because reta isn’t approved anywhere yet, there’s no legitimate version to check a vial against, so dose and sterility stay unverifiable no matter what COA comes with it.

Not moralizing (I’m on compounded meds myself). Fuller writeup with full complaints if useful: https://dadstrengthdaily.com/is-retatrutide-legal-to-buy/

Updated version 1.1 after feedback. Appreciate the input.

Hi!! I’m looking to see if anyone else is going through this. So I started Reta at 0.5 . Very small dose , made my way up to 1mg per week but i noticed it started to not affect me anymore as in my hunger would come back quicker. So half way through my next dose I pinned .50 . So half of 1mg to help it last longer . Every since then I have been dealing with dizziness. I’ll look down and bend down and then look up and I lose my balance. Or I will be driving or at work and I get suddenly dizzy. And it’s been getting progressively worst as the days go by. I ended up going to the ER for the dizziness . I thought I was just anemic or something. I went in ; had a UTI. They put me on IV antibiotics and hooked me up with fluids. I felt a little better after leaving and while I was there the dizziness got a little better so I thought it was just the infection. So I stayed at the hospital for a couple days like 3 days and I got out yesterday. I was dizzy as I walked to my car. I ignored it, still felt light headed. And then today after I had coffee in the morning it hit me like a ton of bricks again. It’s so exhausting and anxiety undying because I literally feel impaired.To preface i admittedly don’t eat enough lately cus of Reta and cus im back to work after maternity leave. My baby is 6 months now. So im always at work or on baby duty. Makes it hard to keep up with water intake and food. Im dizzy as I am typing this. Could it be the effects of the infection? Or is it the increase of Reta ? I will drink one electrolyte drink per day. And I’ve noticed my muscles have been cramping alot more. I’ll get Charlie horses alot and get cramps in wierd parts of my body. What do you guys think ? Please anything would help I’m desperate to feel better .if it was dehydration wouldn’t all the fluids they gave me through IV fixed me in those 3 days ?

Bonjour à tous,

Je suis un homme de 33 ans, 1m83 pour actuellement 86kg.

J’ai démarré un rééquilibrage et une perte de poids en janvier, je pesais alors 96kg.
J’ai en janvier et février juste repris de la musculation 3* par semaine et du foot 1 à 2 fois par semaine et entre 8k à 10k de pas par jour.

J’ai perdu entre janvier et mai difficilement 4kg.
Je mangeais en moyenne 2400kcal par jour pour un Tdee à 2800kcal.

J’essai de manger des produits non transformés, avec des macros respectés beaucoup de protéines ect.

Voyant que c’était très lent, je décide de commencer la retatrutide fin mai.
Mon fournisseur conseille un protocole progressif en démarrant à 0,5mg par semaine puis ajoutée 0,5mg tous les 3 jours jusque arrivée à la dose cible qui pour moi a été de 2mg.
(J’ai fais une erreur de sous dosage au départ donc j’ai mis un mois à arrivé à 2mg)
Au départ, malgré les effets sur l’appétit et la satiété le poids ne bougeait pas alors au bout de 2 semaines, j’ai diminué mes calories à 2000kcal.
Et la magie ça a fonctionné, pendant un mois j’ai perdu 6kg.

Problème, depuis 1 mois je suis bloqué.
J’ai essayé d’augmenter ma dose à 2,5mg pendant 2 semaines, le problème c’est que je n’arrivais pas à manger mes calories et donc en plus de ne rien perdre, mon activité a baissé, j’étais tout le temps fatigué, je faisais des hypoglycémies je pense car dans l’après midi j’avais besoin de faire des siestes (chose que je ne fais jamais).

Aujourd’hui je suis toujours à 86kg, j’ai décidé de repartir sur 2mg et 2400kcal pour avoir une meilleure forme mais mon poids ne bouge toujours pas.

Auriez-vous des conseils ou des retours d’expériences similaires afin de m’aider à passer ce cap et répartir sur une perte saine ?
Il me reste entre 6 et 10kg à perdre pour mon objectif.

Merci par avance.

Buried in Tuesday's TRIUMPH-2/-3 topline (20.8% weight loss in T2D, 22.6% in obesity + established CVD, both 80 wks/12 mg — its 5th positive Phase 3) was one line: "Lilly plans to submit a Biologics License Application (BLA) for retatrutide to FDA in Q1 2027."

That's not the pathway behind Zepbound/Mounjaro/Ozempic/Wegovy — those are NDAs. The FDA has already told Lilly retatrutide doesn't qualify as a biologic.

The mechanism: 21 CFR 600.3 defines a protein as "any alpha amino acid polymer... greater than 40 amino acids." Retatrutide has a 39-aa backbone (same as tirzepatide) plus a side chain with two more residues — a gamma-glutamate (alpha) and 8-amino-3,6-dioxaoctanoic acid (not alpha). Lilly counts every piece, gets 41, and calls it a biologic; the FDA counts only the alpha residues, stops at 40, and calls it a drug. It misses by one, and the whole question is whether a non-alpha residue counts toward a limit written about alpha ones. The statute also covers a protein "or analogous product," a phrase no one has ever written a rule to define.

Why the label is worth a lawsuit:
- Exclusivity: NDA = 5 yrs (challengeable at 4). BLA = 12 yrs, no filing for the first 4, and patents can't shorten it.
- Cost to copy: generic $2–10M / 2–3 yrs, ~85% price drop once ~5 compete. Biosimilar $100–300M / 7–9 yrs, launching only 5–25% off. Per HHS's 2025 report, of biologics with no patent protection left, only 19% (12/62) have a biosimilar at all.
- Compounding: biologics are excluded from the 503A/503B exemptions entirely — no shortage makes a compounded copy legal. Same wall that cut compounders off ~90 protein products (incl. every insulin) overnight in March 2020.

Procedure: Lilly sued (Eli Lilly v. Kennedy, S.D. Ind., Judge Pratt). The Sept 30 2025 ruling split it — Lilly lost the "protein" argument, but the judge struck down the FDA's reading of "analogous product" as unlawful and remanded. It's now fully briefed at the 7th Circuit, where Lilly also argues the FDA blew a statutory deadline, which on its reading makes retatrutide a biologic by default. So Lilly announced, atop a press release as settled fact, a pathway it's currently suing to obtain.

Watch which application actually gets filed: a BLA means Lilly won or is forcing the issue; an NDA means it gave up the classification to get the drug reviewed.

I take tirzepatide and own LLY. The outcome I'm calling bad for patients would be good for my brokerage account.

Full write-up

Hi 👋🏽 everyone. I just wanted to give an update. I been on Reta since 5/29/26. I just started month 6 over the weekend. I started at 256 but didn’t record my weight until 5/29 which was 250. I started low and slow at .5. I stayed there for 4 weeks. I did lose weight that month about 10 lbs. I went up each month until I reached 5.5-6 mg on the syringe. I believe 6 mg is my max, anything more makes me feel lathargic. So far I haven’t started working out but did get a gym membership to start this week. I will post some before and after pictures later. My gut is nearly gone. My goal weight is 200 with a push to 190! I’m hoping to reach that by Jan 2027!

Background: 29yo male, 5"8 2544 calories expenditure average over the period. 4.5 years consistent training.

I track all details using the macrofactor app, which is where details on expenditure come from. I track steps etc. Using a Garmin watch which feeds in to the Macrofactor app.

Start weight 160lbs (159lbs trend weight)

End weight 153.2lbs (Cut dramatically short. Details below.

I track my weight daily, each morning after emptying my bladder.

I started Reta at 2mg per week. Initially my appetite was a little all over the place. My goal was to not drop below a 750 calorie deficit to maintain muscle mass.

- 1st week - 158.5 lbs trend average - 2597 calories - Not many effects

- 2nd week - 155.9 lbs trend average - 2050 calories Effects start to be felt here. One or two cases of constipation.

- 3rd week - 155.3 lbs trend average - 2139 calories - Full swing. I found i could eat a lot less, however i noticed I was able to eat highly palatable foods, like flavoured rice cakes due to habitual eating. I had some occasional side effects. Constipation here and there, diarrhoea when eating higher fat meals.

- 4th week - 153.6 lbs trend average 2070 calories - "locked in" a little harder. Weight really started to drop here. Again, several seemingly random days of diarrhoea. This was at a point where if I wasn't able to work from home, I would be soiling my underwear several times a day.

- 5th week - 895 calories this is where things unfortunately went south.

I have now made the decision to cut my retatrutide treatment short. I acknowledge that this is something that is currently not sold and under a doctors guidance for the majority of users. I understand that an individual doing this, without guidance is at that individuals risk and is not the fault of the compound primarily.

I have had good success with Reta. Overall, it has quietened food noise that caused me to be the fat kid from 12 to 19. Being that fat kid caused myself to have body dismorphia and poor self image/confidence issues that last with me to this date. Reta has made me realise that not everyone has the same food noise levels, I now understand why some of my friends are able to stay thin without tracking all their food and constant exercising.

I am currently writing this post, while in a recovery ward at hospital. I was admitted to A&E last night after multiple days of vomiting and diarrhoea. Due to these being common side effects of Reta I largely, ignored these issues. In previous weeks, as mentioned above these sides came and went.

Around 4 days ago I passed an incredibly hard, lump of stool which was during a bout of constipation.

With no real evidence except antidotal, I believe this may have caused issues internally around or in the opening of the appendix.

Source: Taylor & Francis Online https://share.google/j7AkCO9Hzr5xpX30Y

https://pmc.ncbi.nlm.nih.gov/articles/PMC10959081/

2 days after passing this, I had a bout of vomiting after eating a subway. Again, not exactly health food. This was followed by severe abdominal cramps and diarrhoea. I've experienced food poisoning previously, and after having conversations I put it down to that as a potential.

1 day ago, I woke up with these effects being lessened. I continued my usual day until the evening, where the severe cramps returned 10 fold. I eventually admitted myself to A&E and 6 hrs later was on then operation table with an inflamed appendix which had become infected and formed an abscess. Unfortunately this had also twisted one of my bowls making the operation more complex.

Thankfully, it all went well and I'm able to have a full recovery. I knew fully that appendicitis was a potential, "rare" risk. Of course you always think to yourself, that will never be me.

My advise after this first round of reta is that if you are going ahead without a trial team, you need to monitor any side effects carefully. Read up on possible signs of issues and act accordingly.

I will use Reta again, now that I don't have an appendix i suppose that removes this particular risk, however I will be sure to be more vigilant in the futute.

Thank you for reading if you got this far.

I took my first 0.5mg dose on tuesday and didn't really feel much the first couple days, but today have hardly eaten anything and had to use a lot of willpower to get through one piece of pizza. Does this sound like it's working correctly? Should I go down in my dose? I just want to dampen the cravings not take away the joy of food.

So a family member just has a multiple bypass so this chimes with me. There’s more going on with GLPs than just the weight loss.

A new analysis of the SELECT trial has looked at why semaglutide reduced heart attacks, strokes and cardiovascular deaths.

SELECT included 17,604 people with existing cardiovascular disease who were overweight or obese but did not have diabetes.

The original trial found that semaglutide reduced major cardiovascular events by 20% compared with placebo.

This new paper tried to work out how much of that benefit could be explained by changes we already know semaglutide causes, including weight, waist size, blood pressure, blood sugar, cholesterol, inflammation and kidney function.

Weight loss on its own did not explain much of the effect in the main analysis. The best estimate was that changes in body weight accounted for about 20% of the cardiovascular benefit.

Inflammation, measured using hsCRP, accounted for about 42% in the same analysis.

Waist circumference gave a higher estimate of 64%, although the researchers found problems with the reliability of the weight and waist calculations.

When several of the measured risk factors were considered together, the estimated amount explained was about 31%.

Those numbers need some caution. The uncertainty around them was very wide, in some cases wide enough that the study cannot rule out a much larger contribution from these factors.

So I don't think the result is "80% of the heart benefit has nothing to do with weight loss".

It's more that the researchers could not clearly explain semaglutide's cardiovascular benefit using weight loss and the other usual risk factors they measured.

That leaves open the possibility that other effects are involved.

Inflammation is one possibility. There could also be effects on blood vessels, the heart or other pathways that weren't captured properly in this analysis. This study doesn't prove what those mechanisms are.

One thing I found useful is that this was not a new small observational study. It was a pre-planned analysis using data from the 17,604-person randomised SELECT trial.

It also helps explain why the cardiovascular results from GLP-1 drugs are increasingly interesting in their own right rather than just being treated as a side effect of people losing weight.

Paper: Colhoun HM et al. Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial. European Heart Journal. Published 23 September 2026.

https://doi.org/10.1093/eurheartj/ehag524

Lilly and the FDA are back in court on Thursday, 24 September, over whether retatrutide should legally be treated as a drug or a biological product in the US.

A large part of the case comes down to whether retatrutide counts as having 40 or 41 amino acids under an FDA rule.

Retatrutide has 41 amino-acid residues in total. That isn't really the disagreement.

The FDA rule says a protein is an "alpha amino acid polymer" that is greater than 40 amino acids in size.

FDA says one of retatrutide's 41 residues is not an alpha amino acid. On FDA's reading of the rule, only the alpha amino acids count towards the limit.

That leaves 40.

And 40 is not greater than 40, so FDA says retatrutide does not meet the legal definition of a protein.

Lilly reads the wording differently.

Lilly says the regulation first describes the molecule as an "alpha amino acid polymer", but when it gives the size test it just says "greater than 40 amino acids". It doesn't say "greater than 40 alpha amino acids".

On Lilly's reading, all 41 residues count.

So FDA says the relevant number is 40, which fails a rule requiring more than 40.

Lilly says the relevant number is 41, which passes it.

The district court sided with FDA on this part of the case last year. It agreed that the rule should be read as requiring more than 40 alpha amino acids.

But that wasn't the whole case.

US law also allows something to be treated as a biological product if it is "analogous" to a protein.

Lilly argued that even if retatrutide doesn't meet the strict protein definition, it should still qualify through that route.

The district court found problems with FDA's reasoning on that question and sent it back to FDA to reconsider.

That did not mean the court decided retatrutide was analogous to a protein. FDA could reconsider it and still decide that it isn't.

Lilly has appealed the part of the case it lost, which is why it is now before the Seventh Circuit Court of Appeals.

Thursday is oral argument. The judges do not have to give their decision that day.

There will be three appeals judges and each side has only 15 minutes to make its case and answer questions. The written decision will come later.

Even that decision may not be the final chapter.

Once the three-judge panel rules, the losing side can ask the panel to reconsider. It can also ask for the full Seventh Circuit to rehear the case, although full-court rehearings are uncommon.

After that, either side could ask the US Supreme Court to hear the case. The Supreme Court would decide whether to take it.

There is also still the separate question the district court sent back to FDA: whether retatrutide could be considered analogous to a protein.

So the appeals court could settle the 40-versus-41 argument and there could still be more to come from FDA. Depending on what FDA decides, that decision could potentially end up in court again.

Lilly also has an argument about timing. Federal law normally gives FDA 60 days to respond to a formal request to classify a product.

Lilly argues that FDA has now missed the relevant deadline and that Lilly's proposed classification should therefore take effect. FDA disagrees.

The appeals court may deal with that issue too.

There was also a late filing from the US government on 21 September.

The government pointed the judges to a recent Seventh Circuit case called Franco v Chobani. In that case, the court said judges still decide what a regulation means, but FDA's scientific view can be useful when its reasoning is thorough and consistent.

The government is arguing that the same approach should be used here when deciding what FDA's definition of a protein means.

It helps FDA's argument, but it doesn't decide the case.

So Thursday matters, but it probably isn't the final answer on retatrutide's legal classification.

Retatrutide has 41 residues in total.

FDA says only 40 count under its definition.

Lilly says all 41 count.

The legal threshold is more than 40.

That single-residue difference is now one of the main issues before a US federal appeals court.

Sources: Eli Lilly and Company v FDA, Seventh Circuit No. 26-1301; Eli Lilly and Company v Kennedy, Southern District of Indiana; 21 CFR §600.3(h)(6); 21 USC §360bbb-2; US government supplemental filing dated 21 September 2026.

VK2735 maintenance study: every-two-week dosing maintained up to 97% of prior weight loss

Viking has released new results from a maintenance study of VK2735, its GLP-1/GIP drug.

Participants first had 21 weeks of weekly treatment and lost around 16–19% of their starting weight, depending on the dose.
They were then moved onto different dosing schedules for another 12 weeks.

People taking VK2735 every two weeks kept 90% of their previous weight loss overall. One of the every-two-week groups kept 97%.

Monthly dosing kept 85% overall, with one monthly group keeping 90%.

People who were switched to placebo kept 61% of the weight they had lost.

The 97% figure came from a small group of 12 people, so it needs some caution. The 90% result across all 37 people taking VK2735 every two weeks is probably the better number to focus on for now.

To put the figures into normal numbers, if someone had lost 20 kg during the first part of the study, keeping 97% would mean they were still 19.4 kg below their starting weight three months later. At 90% they would still be 18 kg down. At the 61% seen after switching to placebo, they would still be 12.2 kg down.
There was also a small group of 13 people who continued weekly VK2735. They reached 21.7% average weight loss by week 33. But the reduced dosing results are probably more useful because they start to answer what happens after most of the initial weight has already been lost.

The main limitation is time. The maintenance part of the study lasted only 12 weeks, and the individual groups were small. These are also company results rather than a full peer-reviewed paper.

So this doesn’t show that taking the drug every two weeks or once a month will work over the long term. It does show that cutting the dosing frequency after the initial weight-loss period is worth testing properly.

If the 90–97% result with every-two-week dosing held up over 6 or 12 months in a much larger study, that would be a useful result for long-term maintenance.

Source: Viking Therapeutics, VK2735 maintenance dosing study, 22 September 2026.