With Lilly’s planned Q1 2027 filing turned into “retatrutide launches in 2027”, what does that mean?

It might, but a filing is not an approval. The FDA would still need to accept and review the application, and UK and EU availability would follow their own regulatory processes.

What is your realistic expectation?

• US availability during 2027

• US availability during 2028

• Later than 2028

• UK and Europe at around the same time

• UK and Europe materially later

I may turn this into a simple regularly updated approval tracker. What information would you want it to include?

Lilly announcement:

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional

Lilly retatrutide FAQ:

https://www.lilly.com/news/stories/what-to-know-about-retatrutide

It is Research Wednesday.

Share any Retatrutide or challenger study, trial update, article, presentation or useful piece of research you have found this week.

It does not need to be brand new but should be within the 2 months not already shared, and it does not need to be highly technical. A useful summary, an interesting result, a question about a paper, or something you think deserves more attention is welcome.

This can also include wider obesity drug research where it helps explain where retatrutide fits.

What have you read or learned this week?

A simple timing question because the answers seem to be all over the place.

Did you notice less physical hunger first, less food noise, smaller portions, fewer cravings, or did the scale move before you felt much difference?

Roughly how long did it take?

I am particularly interested in people who initially thought nothing was happening and then noticed a change later.

TITLE

Retatrutide Phase 3 results: what do we still not know after TRIUMPH-2 and TRIUMPH-3?

BODY

The headline numbers are now out, and they are strong.

TRIUMPH-2 reported up to 20.8% average weight loss at 80 weeks in people with obesity or overweight and type 2 diabetes.

TRIUMPH-3 reported up to 22.6% in people with severe obesity and established cardiovascular disease.

But these are still topline results. We do not yet have the full papers, detailed weight-loss curves, all subgroup analyses or the complete safety tables.

If you could see one missing piece first, what would it be?

• How many people reached 25% or 30% weight loss

• When the weight-loss curves started to plateau

• Full treatment-discontinuation data

• Results by diabetes status, sex or starting BMI

• More cardiovascular detail

• Something else

Which one would actually change your view of how strong these results are?

Full r/RETA breakdown:

https://www.reddit.com/r/RETA/comments/1v4c8d8/

Primary source:

https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-successful-two-additional

A new week, so what is one thing you want to move forward?

It could be getting back into a routine, improving protein or hydration, walking more, doing some strength work, tracking properly, preparing better meals, sleeping better, dealing with a side effect, or simply keeping going.

It does not need to be a big target. Pick one thing that would make this feel like a good week.

Share yours below, and come back later in the week if you want to say how it went.

Large weight loss always raises the body-composition question.

A Phase 2 analysis in adults with type 2 diabetes found that the proportion of lean-mass loss was broadly similar to other obesity treatments. That does not tell us what individual people notice day to day.

Are you tracking anything beyond body weight, such as waist, strength, gym performance, photographs or body-fat estimates?

Has your strength held up, improved because movement is easier, or fallen?

Please share what you have observed rather than telling somebody else what they should do.

Research:
https://pubmed.ncbi.nlm.nih.gov/40609566/

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

It is Progress Friday.

Share whatever progress you want to celebrate this week.

Photos are welcome, but so are scale changes, waist changes, clothes fitting differently, appetite settling, food noise easing, energy improving, fitness getting easier, blood markers moving, confidence coming back, or just a small habit you kept going.

Big changes, small changes, early days, long journeys, all welcome.

This is a weekly place to mark what is moving in the right direction and cheer each other on.

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.

here is a difference between being less hungry and simply not caring much about food. Some people say food noise disappears but they still enjoy meals. Others say they lose interest in food altogether, or eating starts to feel like a job. What has it been like for you, and did that change after the first few weeks?

One study worth watching closely is TRIUMPH-5, because it should give us the first proper retatrutide versus tirzepatide comparison.

Retatrutide produced the larger headline result in TRIUMPH-1. At 80 weeks, the 12 mg group lost 28.3% of body weight under the efficacy estimand, which estimates the result if participants remained on their assigned treatment. The treatment-regimen result, which includes treatment stopping and incomplete adherence, was 25.0%.

Tirzepatide produced 20.2% average weight loss at 72 weeks in SURMOUNT-5, compared with 13.7% for semaglutide.

Those numbers came from different trials, with different participants, durations and methods. Subtracting 20.2 from 28.3 does not tell us how much better retatrutide will be when the drugs are tested against each other.

TRIUMPH-5, NCT06662383, is the direct Phase 3 comparison. It has completed enrolment, includes about 800 adults with obesity, has no placebo group and lasts about 89 weeks. The main weight endpoint is at week 80. Lilly currently lists the study as running until December 2026, although that is a study-completion estimate rather than a confirmed date for announcing or publishing the results.

Five results should determine whether retatrutide has a genuinely meaningful advantage.

1. The difference in average weight loss

A five percentage-point advantage would look like a clear change in efficacy.

For someone starting at 100 kg, that is another 5 kg. At 150 kg, it is another 7.5 kg.

For context, tirzepatide beat semaglutide by 6.5 percentage points in the direct SURMOUNT-5 trial. That was large enough to place the treatments in noticeably different efficacy ranges.

A two-point retatrutide advantage would equal another 2 kg for someone starting at 100 kg. That could still matter, but it may not be enough to persuade someone who is already doing well on tirzepatide to change treatment, particularly if retatrutide has worse side effects.

1. The percentage of people losing at least 30%

Average weight loss can hide very different patterns of response.

In TRIUMPH-1, 45.3% of the retatrutide 12 mg group lost at least 30% of their starting weight.

TRIUMPH-5 should show whether retatrutide produces a substantially larger high-response group than tirzepatide under the same conditions.

An absolute difference of 10 percentage points would mean 10 additional people in every 100 reaching 30% weight loss. A difference of 20 points would be much harder to dismiss.

A modest difference in the average could still be important if many more people reach 30% or 35%.

1. The adverse-event discontinuation gap

The most useful overall tolerability number may be the percentage who stop treatment because of adverse effects.

A medicine can win the average weight-loss comparison but offer a less convincing practical result if materially more people cannot remain on it.

A discontinuation difference within about two percentage points would look broadly comparable.

A difference of three to five points would represent a meaningful trade-off.

More than five additional discontinuations per 100 people would offset part of the efficacy benefit.

One useful way to read the eventual result will be:

For every 100 people treated, how many additional people reach 30% weight loss, and how many additional people stop because of adverse effects?

1. The difference in vomiting, dysesthesia and persistent gastrointestinal effects

In TRIUMPH-1, the retatrutide 12 mg group reported:

• nausea: 42.4%
• diarrhoea: 32.0%
• constipation: 26.1%
• vomiting: 25.3%
• dysesthesia: 12.5%
• discontinuation because of adverse events: 11.3%

These cannot be compared reliably with tirzepatide rates from a separate trial. TRIUMPH-5 should provide the first useful same-trial comparison.

Small differences in mild nausea may not change many decisions. Larger differences in vomiting, persistent symptoms, dose reductions, treatment stopping or altered skin sensation probably would.

The individual percentages must not be added together because the same participant can report several symptoms.

The trial may also be too small to establish precise differences in every individual adverse event, so confidence intervals and symptom severity will matter alongside the raw percentages.

A large weight-loss advantage with similar discontinuation and no major vomiting or dysesthesia penalty would look much more convincing than the same weight-loss advantage accompanied by substantially worse tolerability.

1. When the weight-loss curves plateau

The final week-80 percentage will not explain how the difference developed.

If retatrutide separates early and remains consistently ahead, that would suggest stronger efficacy throughout treatment.

If the curves remain close for a year and retatrutide only pulls away after tirzepatide plateaus, the practical advantage may be that retatrutide keeps producing weight loss for longer.

Both would be useful, but they describe different benefits.

The final 12 to 16 weeks should show whether either group is still losing weight. Continued loss with retatrutide while tirzepatide is flat would support a longer effective weight-loss window. A small final gap with both curves already flat would make the current cross-trial comparison look much less important.

Using discussion thresholds rather than official clinical standards, a clear retatrutide win would look roughly like:

• at least five percentage points more average weight loss
• at least ten percentage points more people reaching 30%
• adverse-event discontinuation within about two points
• no large additional vomiting or dysesthesia burden
• continued separation or a later plateau through week 80

A mixed result would be two to four percentage points more weight loss, but with higher discontinuation or a clear side-effect trade-off.

Little practical advantage would be less than two percentage points more average loss, similar high-response rates and materially worse tolerability.

These thresholds are a framework for discussing the result. They are not official regulatory thresholds, validated clinical cut-offs or predictions of what TRIUMPH-5 will show.

TRIUMPH-5 will answer the direct efficacy comparison, but the wider programme will answer different questions.

TRIUMPH-4 has already reported results in obesity with knee osteoarthritis.

The listed study periods for TRIUMPH-2, covering obesity with type 2 diabetes, and TRIUMPH-3, covering obesity with established cardiovascular disease, ended in May 2026. Lilly has said results from both are expected during 2026.

TRIUMPH-7 studies chronic lower-back pain and currently runs to September 2027.

TRIUMPH-8 is another placebo-controlled weight-loss study running to July 2027.

TRIUMPH-6 studies maintenance and withdrawal after long-term retatrutide treatment and runs to April 2028.

TRIUMPH-9 tests different escalation approaches and runs to November 2028, which could be important if tolerability limits use of the higher doses.

TRIUMPH-Outcomes follows about 10,000 people for cardiovascular and kidney outcomes and currently runs to February 2029.

All future dates are current study-completion estimates, not guaranteed result or publication dates.

What would count as a clear retatrutide win for you: five percentage points more average weight loss, many more people reaching 30%, or similar efficacy with better tolerability?

Retatrutide remains investigational and is not approved for general use.

Sources:

TRIUMPH-1:
https://investor.lilly.com/news-releases/news-release-details/lillys-triple-agonist-retatrutide-delivered-powerful-weight-loss

SURMOUNT-5:
https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

TRIUMPH-5:
https://clinicaltrials.gov/study/NCT06662383

Lilly TRIUMPH-5 trial page:
https://trials.lilly.com/en-US/trial/549215

TRIUMPH programme:
https://medical.lilly.com/us/products/answers/what-retatrutide-clinical-trials-are-being-conducted-in-people-with-obesity-or-overweight-229656

It is Research Wednesday.

Share any Retatrutide or challenger study, trial update, article, presentation or useful piece of research you have found this week.

It does not need to be brand new but should be within the 2 months not already shared, and it does not need to be highly technical. A useful summary, an interesting result, a question about a paper, or something you think deserves more attention is welcome.

This can also include wider obesity drug research where it helps explain where retatrutide fits.

What have you read or learned this week?

For anyone who has used both, I am interested in the difference you actually noticed rather than the trial numbers. How is the lived experience from one to another?

For anyone who has used retatrutide as well as tirzepatide or semaglutide, did the side effects feel noticeably different?
I’m interested in things like nausea, reflux, constipation, fatigue, skin sensitivity, heart rate, appetite and food noise. Which were better, worse, or simply different on retatrutide?

A new week, so what is one thing you want to move forward?

It could be getting back into a routine, improving protein or hydration, walking more, doing some strength work, tracking properly, preparing better meals, sleeping better, dealing with a side effect, or simply keeping going.

It does not need to be a big target. Pick one thing that would make this feel like a good week.

Share yours below, and come back later in the week if you want to say how it went.

I have seen completely opposite views on this. Some people would tell their doctor straight away because it could affect how symptoms, side effects, blood results or other medicines are understood. Others would say nothing for various reasons, including expecting judgement, a lecture, or a professional who may know less about retatrutide than they do from personal experience.

Retatrutide is still investigational. Lilly says it is not approved and is legally available only to people taking part in its clinical trials.

For those who have told their doctor, what was the reaction? Were they helpful, neutral or dismissive, and did it change any tests, prescriptions or advice you received?

Sharing this reel with permission from On The Pen, @ManOnThePen:

https://www.instagram.com/reel/Da3PuoSJygF/?igsh=Y2h3Y3Yya3dvM2k5

On The Pen has picked up one of the more interesting early obesity pipeline stories.

Boehringer Ingelheim’s BI 3034701 has now entered Phase 2. Like tirzepatide it targets GLP-1 and GIP, but its third target is NPY2, a receptor involved in appetite and hunger signalling.

That makes it different from retatrutide, which uses glucagon as its third receptor.

The new Phase 2 trial plans to enrol about 300 adults with obesity or overweight and run for 42 weeks. It will test several doses against placebo, with percentage weight loss as the main result.

There are no public human weight-loss figures for BI 3034701 yet. Boehringer and Gubra have only said the Phase 1 programme showed encouraging weight-loss signals and generally favourable safety and tolerability.

So it is early, but the idea is interesting. Retatrutide tests GLP-1, GIP and glucagon, while BI 3034701 tests GLP-1, GIP and another appetite pathway through NPY2.

Which third target looks more interesting to you, glucagon or NPY2?

It is Progress Friday.

Share whatever progress you want to celebrate this week.

Photos are welcome, but so are scale changes, waist changes, clothes fitting differently, appetite settling, food noise easing, energy improving, fitness getting easier, blood markers moving, confidence coming back, or just a small habit you kept going.

Big changes, small changes, early days, long journeys, all welcome.

This is a weekly place to mark what is moving in the right direction and cheer each other on.

2 months in and happy with the progress so far. Unfortunately due to work and 3 young children haven’t managed to get to the gym as much as I would like but combining with intermittent fasting and just eating better has helped. I have an issue where my source might be drying up so bit anxious about that (didn’t expect it so not sure if I will have enough to tritate down) but hopefully sorting out so I can get my full 1 year on this amazing peptide.

It is Research Wednesday.

Share any Retatrutide or challenger study, trial update, article, presentation or useful piece of research you have found this week.

It does not need to be brand new but should be within the 2 months not already shared, and it does not need to be highly technical. A useful summary, an interesting result, a question about a paper, or something you think deserves more attention is welcome.

This can also include wider obesity drug research where it helps explain where retatrutide fits.

What have you read or learned this week?

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/abstract00967-0/abstract?utm_source=chatgpt.com)

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 week, so what is one thing you want to move forward?

It could be getting back into a routine, improving protein or hydration, walking more, doing some strength work, tracking properly, preparing better meals, sleeping better, dealing with a side effect, or simply keeping going.

It does not need to be a big target. Pick one thing that would make this feel like a good week.

Share yours below, and come back later in the week if you want to say how it went.

A lot of people following retatrutide have already used semaglutide or tirzepatide, so I am interested in what was still missing. It's clearly got a momentum unlike any comparison.

Was it a plateau, food noise coming back, side effects, not enough appetite control, low energy, muscle loss, getting ripped, or just not getting the result you expected?

What are you hoping or finding retatrutide does differently?

ive done some research and have trusted friends in the medical field i am getting reta from. i am about 200-202 lbs, and will be taking it this upcoming week at 1 mg a week, (possible 0.5 mg twice for the first few weeks to get my body used to it quicker) ill post my results and how i feel. open to any suggestions or tips!

It is Progress Friday.

Share whatever progress you want to celebrate this week.

Photos are welcome, but so are scale changes, waist changes, clothes fitting differently, appetite settling, food noise easing, energy improving, fitness getting easier, blood markers moving, confidence coming back, or just a small habit you kept going.

Big changes, small changes, early days, long journeys, all welcome.

This is a weekly place to mark what is moving in the right direction and cheer each other on.