Peptide Decoding
All comparisons
Compare / Three-way comparison

Semaglutide vs Tirzepatide vs Retatrutide

Two of these three have been compared head to head. The third has only ever been compared with placebo.

  • ONE HEAD-TO-HEAD TRIAL EXISTS
  • RETATRUTIDE NOT APPROVED ANYWHERE
  • NO DOSING GUIDANCE ON THIS PAGE
Published October 18, 2026 · Updated October 26, 2026
Part of our Semaglutide coverage: Semaglutide.
Semaglutide, tirzepatide and retatrutide research vials
At a glance

Two compared head to head. The third, only against placebo.

Tirzepatide beat semaglutide by 6.5 percentage points in SURMOUNT-5, the only head-to-head trial among the three. Retatrutide's larger number has never been tested against either drug. The figures people line up, roughly 15, 22.5 and 28.3 percent, come from STEP 1, SURMOUNT-1 and TRIUMPH-1, three trials of different lengths that do not use the same statistical convention.

Semaglutide research vial
GLP-1 · Approved

Semaglutide

The oldest of the three, with the longest human record. Approved for diabetes, weight and cardiovascular risk.

Tirzepatide research vial
GIP + GLP-1 · Approved

Tirzepatide

The only one tested head to head against another drug here. It beat semaglutide by 6.5 points in SURMOUNT-5.

Retatrutide research vial
Triple agonist · In trials

Retatrutide

The largest weight-loss number of the three, from a trial against placebo only. Never tested against either drug.

01 / Comparison

The short version

Semaglutide Tirzepatide Retatrutide
Receptors GLP-1 GIP + GLP-1 GIP + GLP-1 + glucagon
Approved for weight loss Yes, Wegovy Yes, Zepbound No. Nowhere
Pivotal trial STEP 1, 68 weeks 1 SURMOUNT-1, 72 weeks 2 TRIUMPH-1, 80 weeks 4
Participants 1,961 1 2,539 2 2,339 4
Headline loss 14.9% 1 22.5% 3 28.3% 7
Which estimand that is Counts everyone Assumes everyone stayed on Assumes everyone stayed on
Tested against another drug? Yes, lost to tirzepatide 5 Yes, beat semaglutide 5 Never
Median vendor price per mg $8.00 $4.75 $7.33
At its own trial dose $19 per week $71 per week $88 per week
Vendors we track selling it 85 94 111

Price figures are from our 5 October 2026 capture of 158 vendors and move constantly. 13

02 / Comparison

Which one produced the most weight loss?

Retatrutide, on the raw numbers, and the raw numbers are the problem.

At the top dose in each pivotal trial, semaglutide 2.4 mg produced 14.9 percent weight loss over 68 weeks, tirzepatide 15 mg produced 22.5 percent over 72 weeks, and retatrutide 12 mg produced 28.3 percent over 80 weeks. 137 That is the ladder everyone quotes, and the ranking is almost certainly right in direction.

The size of each step is where it falls apart. Those three figures are not the same measurement. Two of them assume every participant stayed on the drug for the whole trial, and one of them counts everybody who started including the people who quit. Lining them up side by side compares a best case against an average.

STEP 1, SURMOUNT-1 and TRIUMPH-1. 3 trials, 3 durations, 2 incompatible conventions.

When the three are put on the same footing, the gap between semaglutide and tirzepatide narrows from 7.6 points to somewhere between 5.3 and 6.0. 13 The gap between tirzepatide and retatrutide moves even more, from 5.8 points down to as little as 3.3, or up to 6.0, depending on which defensible method you pick. 347

One of those two gaps has been measured in a randomized trial. The other has not.

03 / Comparison

Are the three headline numbers actually comparable?

No, and the reason is a word most coverage never prints: estimand.

A large obesity trial reports its result more than once, because there is more than one honest question to ask. One question is what the drug does to someone who takes it as directed for the full trial. The other is what happens on average to everyone handed a prescription, including the people who stop because the nausea is intolerable. Both are legitimate. They give different numbers, and the second is always smaller.

The trouble is that Novo Nordisk and Eli Lilly use different names for the same two ideas.

What is being estimated Novo Nordisk calls it Eli Lilly calls it
Effect if everyone had stayed on the drug Trial product estimand 1 Efficacy estimand 3
Effect counting everyone who started Treatment policy estimand 1 Treatment-regimen estimand 3

Lilly's own definition of the efficacy estimand is that it "represents efficacy prior to discontinuation of study drug," and of the treatment-regimen estimand that it "represents the estimated average treatment effect regardless of treatment discontinuation." 3 Novo's two estimands in STEP 1 answer those same two questions under the other pair of names. 1

Novo and Lilly. 2 sponsors, 2 vocabularies, 1 number quoted out of each.

Here is what each drug looks like under each convention, at its top dose in its own pivotal trial.

Semaglutide 2.4 mg, 68 wk Tirzepatide 15 mg, 72 wk Retatrutide 12 mg, 80 wk
Assuming everyone stayed on drug 16.9% 1 22.5% 3 28.3% 7
Its placebo arm 2.4% 1 2.4% 3 2.2% 7
Counting everyone who started 14.9% 1 20.9% 3 25.0% 4
Its placebo arm 2.4% 1 3.1% 3 3.9% 4

Now read the numbers people actually quote. The familiar trio is STEP 1's 14.9, SURMOUNT-1's 22.5 and TRIUMPH-1's 28.3. The first comes from the bottom half of that table and the other two come from the top half. The comparison takes semaglutide's average-including-quitters and sets it against tirzepatide's and retatrutide's if-everyone-stayed.

Put all three on "assuming everyone stayed on drug" and the ladder reads 16.9, 22.5 and 28.3. 137 Put all three on "counting everyone who started" and it reads 14.9, 20.9 and 25.0. 134 Both are defensible. Neither is the trio in circulation.

Subtract each trial's own placebo arm and the picture shifts again, because the placebo arms are not identical. STEP 1's placebo group lost 2.4 percent, SURMOUNT-1's lost 3.1 percent and TRIUMPH-1's lost 3.9 percent on the counting-everyone basis. 134 A 1.5 point spread across three placebo groups is not noise to be ignored. It is the thing a placebo arm exists to subtract.

Placebo-adjusted, counting everyone who started
Semaglutide 12.5 points 1
Tirzepatide 17.8 points 3
Retatrutide 21.1 points 4

That is the most honest single ranking on this page, and it is still a comparison of three separate trials.

04 / Comparison

What happened when semaglutide and tirzepatide were actually compared?

Tirzepatide won SURMOUNT-5 by 6.5 percentage points, and this is the only pairing among the three where that sentence can be written at all.

SURMOUNT-5 randomized 751 adults with obesity and without diabetes to tirzepatide or semaglutide for 72 weeks, each at the maximum dose the participant tolerated. 5 Tirzepatide reached 20.2 percent weight loss against semaglutide's 13.7 percent, with p below 0.001. 5 Waist circumference fell 18.4 cm against 13.0 cm. 5 Published in the New England Journal of Medicine in 2025, it remains the only randomized head-to-head trial of two of these three drugs.

SURMOUNT-5. 751 adults, 72 weeks, 6.5 points, and 1 design flaw worth knowing.

The flaw is that SURMOUNT-5 was open-label. Everyone knew which drug they were taking. In a trial whose primary endpoint is body weight and where both arms require participants to keep taking an injection through months of gastrointestinal side effects, knowing you are on the newer drug that the headlines favor is not a trivial thing. It is the single biggest reason to hold this result a little loosely.

And here is the part worth sitting with. Comparing STEP 1 against SURMOUNT-1 four different ways gives a semaglutide-to-tirzepatide gap of 5.3, 5.6, 5.6 and 6.0 points. 13 SURMOUNT-5 then measured it at 6.5. 5 The cross-trial estimates came within about a point of the measured answer.

That cuts two ways, and the page is not going to pretend otherwise. It is modest evidence that careful cross-trial comparison of drugs in this class can land close to the truth. It is also a sample of one, and we only know it landed close because somebody spent the money to run the trial. The mixed-estimand figure of 7.6 points that circulates widely overstated SURMOUNT-5's measured gap by 17 percent, so even here the sloppy version was the one that missed.

Nobody has run the blinded version. Nobody has run anything at all involving retatrutide and an active comparator.

The three research-labeled vials side by side
Three vials, three different evidence positions.
05 / Comparison

How much does the method change the retatrutide gap?

The method nearly doubles it, from 3.3 points to 6.0 points, and no trial exists to settle which is right.

TRIUMPH-1 published in the New England Journal of Medicine on 29 September 2026, so retatrutide's Phase 3 is no longer a press release. 4 TRIUMPH-1 randomized 2,339 adults with obesity and without diabetes across 131 sites in 11 countries to 4, 9 or 12 mg weekly or placebo for 80 weeks. 4 That is a real trial with a real methods section, and the result is large.

What it is not is a comparison with tirzepatide. Here is the tirzepatide-to-retatrutide gap by four defensible routes.

Method Gap
As usually quoted, 22.5 vs 28.3 5.8 points
Both on counting-everyone, 20.9 vs 25.0 4.1 points
Placebo-adjusted, assuming-everyone-stayed 6.0 points
Placebo-adjusted, counting-everyone 3.3 points

A tirzepatide-to-retatrutide gap ranging from 3.3 to 6.0 points depending on bookkeeping is not a settled finding. For the semaglutide-to-tirzepatide pair the equivalent spread was 5.3 to 6.0, a much tighter range, and SURMOUNT-5 existed to check it against. For this pair the spread is wider and there is nothing to check it against.

SURMOUNT-1 against TRIUMPH-1. 1 gap, 4 defensible methods, 2.7 points of disagreement.

Two more things make this pairing harder to read than the other one.

TRIUMPH-1 ran 8 weeks longer than SURMOUNT-1 and 12 weeks longer than STEP 1. 124 A crude correction, dividing each drug's placebo-adjusted loss by its trial length, puts semaglutide at 1.8 points per 10 weeks, tirzepatide at 2.5 and retatrutide at 2.6. 134 On that arithmetic tirzepatide and retatrutide are near-identical and most of the gap is the extra time. That arithmetic is also wrong in a specific direction, because weight loss in these trials flattens rather than continuing in a straight line, so the later weeks contribute less than the early ones and dividing by weeks penalizes the longest trial. Treat it as a reason for caution, not as a result.

TRIUMPH-1 also enrolled a heavier group. Mean BMI was about 40, against 37.9 in STEP 1 and 38.0 in SURMOUNT-1. 124 Heavier starting populations tend to post larger percentage losses. All three trials excluded participants with diabetes, so that particular confound is absent. 124

06 / Comparison

What does each one do inside the body?

Semaglutide copies one gut hormone, tirzepatide copies two, and retatrutide copies two and adds a third signal that works in the opposite direction.

Semaglutide is a GLP-1 receptor agonist. GLP-1 is released from the gut after eating and it slows stomach emptying, increases insulin release when glucose is high, and acts on appetite centers in the brain. 10

Tirzepatide hits GLP-1 and also GIP, a second gut hormone. The GIP contribution is the part of this class that is least settled mechanistically, because GIP receptor agonism and GIP receptor blockade have both been argued to help with weight. Tirzepatide's results establish that the combination works without settling why. 11

Retatrutide adds glucagon receptor agonism to those two. This is the interesting one, because glucagon's familiar job is raising blood sugar, which sounds like the wrong direction entirely. The proposed benefit is that glucagon receptor activity raises energy expenditure and acts on liver fat, so the two incretin receptors reduce what goes in while the third raises what goes out. 6

Wegovy 1 receptor, Zepbound 2, retatrutide 3, with the 3rd pulling the other way.

The receptor count is also why the ladder is intuitively appealing and why that appeal should be resisted. More receptors producing more weight loss is a tidy story, and the one place it was tested directly, SURMOUNT-5, it held. 5 But receptor count is not a dose and it is not a mechanism of action in a person. Nothing guarantees the pattern keeps going, and a fourth receptor would not be expected to add another six points simply because the first three did.

07 / Comparison

What do the side effect tables show side by side?

Gastrointestinal effects in all three, rising with dose, and one effect that only retatrutide reports.

At the top dose Semaglutide 2.4 mg 1 Tirzepatide 15 mg 3 Retatrutide 12 mg
Nausea 44.2% 31.0% about 41% 7
Diarrhea 31.5% 23.0% not published by percentage
Vomiting 24.8% 12.2% not published by percentage
Constipation 23.4% 11.7% not published by percentage
Stopped for adverse events 7.0% 6.2% 11.2% 4
Its placebo arm stopped 3.1% 2.6% 4.6% 4

Two things stand out.

Semaglutide's nausea rate is the highest in that table, at 44.2 percent against tirzepatide's 31.0 percent, and semaglutide is the drug with the smallest weight loss of the three. 13 The side effect burden does not line up neatly with the benefit. Anyone assuming the gentlest drug is the weakest one has it backwards here.

Retatrutide's discontinuation rate is the outlier. 11.2 percent of participants on 12 mg stopped for adverse events, against 6.2 percent on tirzepatide 15 mg and 7.0 percent on semaglutide 2.4 mg. 134 Retatrutide's 11.2 percent, roughly one in nine, is also the mechanism by which the two estimands pull apart, which is why its two figures sit 3.3 points apart while semaglutide's sit 2.0 points apart. 147

In TRIUMPH-1, 11.2% stopped on retatrutide, against 6.2% and 7.0% on the approved two.

Retatrutide also reports dysesthesia, altered skin sensation, at 5.1 to 12.5 percent across its dose arms against 0.9 percent on placebo. 7 The Wegovy and Zepbound labels do not list it at comparable rates. 1011 Whether it is a glucagon receptor effect is not established.

All three sit in a class carrying a boxed warning for thyroid C-cell tumors, based on rodent findings. 1011 In January 2026 the FDA asked for the warning about suicidal thoughts and behavior to be removed from the obesity versions of this drug family after a review found no increased risk, and labels were updated in February 2026.

08 / Comparison

What does each cost, and why does the ranking invert?

Market snapshot · October 5, 2026

Semaglutide is the most expensive of the three per milligram and by far the cheapest per week, because STEP 1 dosed it at 2.4 mg against tirzepatide's 15 mg in SURMOUNT-1 and retatrutide's 12 mg in TRIUMPH-1. 124

This is the part most comparisons get wrong by never doing the arithmetic. Our 5 October 2026 capture covers 158 vendors. 13

Median price per mg Dose in its pivotal trial Cost per week at that dose
Semaglutide $8.00 (dearest) 2.4 mg 1 $19 (cheapest)
Tirzepatide $4.75 (cheapest) 15 mg 2 $71
Retatrutide $7.33 12 mg 4 $88 (dearest)

The per-milligram ranking and the per-week ranking are exact opposites for the two ends. Tirzepatide is the cheapest of the three by the milligram and the second most expensive by the week. Semaglutide is the dearest by the milligram and roughly a quarter of retatrutide's weekly cost, because it is dosed at a fifth of the milligrams.

In our 2026 capture, $8.00 per mg buys the cheapest week and $4.75 per mg the second dearest.

Price per milligram is the number almost every vendor page leads with, and on its own it tells you close to nothing about what a protocol costs. A drug's milligram count is a property of its potency, not of its value.

Spreads within each compound are enormous. Semaglutide ranges from $1.00 to $112.79 per mg across 124 clean single-vial listings, tirzepatide from $0.07 to $95.00 across 226, and retatrutide from $1.45 to $76.00 across 258. 13 A hundredfold spread inside one compound is not a market pricing quality. Nothing in a price tells you what is in the vial.

For comparison, the approved products through official channels run on a completely different scale, with manufacturer self-pay programs in the few hundred dollars per month and retail list prices around $1,000 to $1,350 per month. 12 Those are regulated products with an identified manufacturer. The figures in the table above are research chemicals sold by vendors with no such accountability.

09 / Comparison

What is actually on sale, and under what names?

Market snapshot · October 5, 2026

Retatrutide, the only one of the three not approved anywhere, has the widest gray-market supply of the three.

Listings Vendors Alias codes in our library
Semaglutide 180 85 17
Tirzepatide 285 94 27
Retatrutide 345 111 34

Retatrutide carries the most listings, the most vendors and twice as many alias codes as semaglutide. 13 Of the 158 vendors in the capture, 120 sell at least one of the three and 71 sell all three. 13 17 sell retatrutide and neither of the others, and 34 sell retatrutide but not semaglutide. 13

In our 2026 capture, 111 vendors sell the 1 drug no regulator has approved.

The alias lists are the most telling part. Retatrutide's 34 alias codes include GLP-3, triple G, Trinity-X, RETA-10 and ratatouille. 13 "GLP-3" is not a real receptor designation and there is no such hormone. "Ratatouille" is a phonetic dodge. These are not scientific synonyms or trade names, they are search-and-filter evasion codes, and the volume of them is a measure of how much pressure the sellers are under.

That pressure is real. On 12 August 2026 Lilly filed six federal lawsuits against US sellers of black-market retatrutide. Lilly has said it plans to file for FDA approval in the first quarter of 2027, pushed back from an earlier timeline while manufacturing and quality data are assembled.

What is in the vials is the open question. A 2018 analysis of seized peptide products found purity ranging from 5 to 75 percent. 14 That study was not of these three compounds, and we are not going to claim it was. It is the best published measurement available of what unregulated peptide supply chains actually deliver, and the direction of the finding is the relevant part.

Anything sold under these names outside a pharmacy was not made in the facility that supplied any trial on this page. The trial results describe a characterised molecule at a known dose. They do not transfer to a vial of unknown content.

10 / Comparison

Which are approved, and for what?

Two of the three are approved for weight loss. The third is not approved for anything, anywhere.

Weight loss Type 2 diabetes Cardiovascular
Semaglutide Wegovy 10 Ozempic Yes, in people with obesity and established cardiovascular disease 8
Tirzepatide Zepbound 11 Mounjaro Non-inferior to dulaglutide in SURPASS-CVOT 9
Retatrutide No No No trial powered for it 4

Semaglutide has the strongest cardiovascular evidence of the three. SELECT randomized 17,604 adults and found a 20 percent relative reduction in major adverse cardiovascular events. 8 Tirzepatide's SURPASS-CVOT compared it with dulaglutide, an active comparator rather than placebo, across 13,299 adults with diabetes. 9

Retatrutide has nothing here. TRIUMPH-1 reported that pancreatitis and major adverse cardiovascular events were uncommon, with too few events for firm conclusions, and the trial was not powered for cardiovascular safety. 4 That is the correct way to report it and it means the question is open rather than answered favorably.

Wegovy and Zepbound carry 2 approvals each. Retatrutide carries 0.

All three are prohibited at all times in sport under the World Anti-Doping Agency code's S4 category covering metabolic modulators, which applies regardless of a drug's approval status.

11 / Comparison

What has nobody answered?

Four questions, and the first one is the whole page.

Nobody has compared retatrutide with anything but placebo. Every retatrutide-versus-tirzepatide number in circulation is an inference across trials, and that inference ranges from 3.3 to 6.0 points depending on method. 34 A head-to-head would settle it. None has been run, and Lilly has no commercial reason to run one against its own tirzepatide.

Nobody has run a blinded head-to-head of any pair. SURMOUNT-5 is open-label. 5 It is the best evidence in this comparison and its design is the weakest part of it.

Nobody has published how much of the loss is fat. None of the three pivotal trials reported body composition as a primary endpoint. 124 At TRIUMPH-1's 25 percent total body weight loss, the question of what fraction is lean mass stops being academic, and for retatrutide there is no published answer. 4

Nobody knows what happens after the trial ends. The STEP 1 extension found substantial weight regain after semaglutide was withdrawn. 1 No equivalent withdrawal data exists for retatrutide. TRIUMPH-1's 80-week result says nothing about year five. 4

Common questions

Questions people ask

Common questions

Is retatrutide better than tirzepatide?

Retatrutide produced a larger number in its own trial. The two have never been compared directly, and the estimated gap ranges from 3.3 to 6.0 percentage points depending on the method used. 34

Which of the three produced the most weight loss?

Retatrutide, at 28.3 percent over 80 weeks. 7 That figure assumes every participant stayed on the drug, and 11.2 percent did not. 4

Has semaglutide ever beaten tirzepatide?

No. SURMOUNT-5 compared them directly and tirzepatide won by 6.5 percentage points. 5

Is retatrutide FDA approved?

No. It is not approved in any country. Lilly has said it plans to file for FDA approval in the first quarter of 2027.

Why do different sites give different numbers for the same trial?

Because each trial reports two results, and most coverage picks one without saying which. Retatrutide's two figures are 28.3 and 25.0 percent, and both are correct. 47

What is an estimand?

It is the specific question a trial result answers. One estimand asks what the drug does to people who keep taking it. The other asks what happens on average to everyone who starts, including those who stop. 3

Which estimand should I be looking at?

The one counting everyone who started is closer to what happens in practice, because people do stop. Just make sure all the numbers you are comparing use the same one.

Is the gap between semaglutide and tirzepatide really 47 percent?

The 47 percent figure is SURMOUNT-5's 6.5 point absolute difference expressed as a proportion of semaglutide's result. Both describe SURMOUNT-5 accurately. 5 The absolute figure is the more useful one.

Why is semaglutide cheaper per week if it costs more per milligram?

Its trial dose is 2.4 mg a week against tirzepatide's 15 mg and retatrutide's 12 mg. 124 At $8.00 per mg that works out to about $19 a week. 13

Does the third receptor actually do anything?

Glucagon receptor activity is proposed to raise energy expenditure and act on liver fat, so it works in the opposite direction to the other two. 6 Its specific contribution has not been isolated in a trial.

Why does retatrutide have so many names?

Our library records 34 alias codes for it, including GLP-3 and ratatouille. 13 They are search-evasion codes used by sellers, not scientific synonyms. There is no GLP-3 receptor.

Is dysesthesia a real concern?

Dysesthesia was reported in 5.1 to 12.5 percent of retatrutide participants against 0.9 percent on placebo. 7 The Wegovy and Zepbound labels do not list it at comparable rates. 1011

Did all three trials exclude people with diabetes?

Yes. STEP 1, SURMOUNT-1 and TRIUMPH-1 all enrolled adults without diabetes. 124

Were the three trials the same length?

No. 68, 72 and 80 weeks respectively, with retatrutide's the longest. 124

Which has the best cardiovascular evidence?

Semaglutide. SELECT found a 20 percent relative reduction in major cardiovascular events across 17,604 adults. 8 Retatrutide has no trial powered for it. 4

Is what is sold online the same as what was in the trials?

No. What is sold online was not made in the facility that supplied any trial on this page, and a 2018 analysis of seized peptide products found purity ranging from 5 to 75 percent. 14

Are they banned in sport?

Yes, all three, at all times, under the WADA code's S4 metabolic modulators category. Approval status makes no difference.

References

What this page is built on

  1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. DOI 10.1056/NEJMoa2032183. NCT03548935. STEP 1. 1,961 adults randomized 2:1, 68 weeks, 2.4 mg weekly reached by week 16. Treatment policy estimand −14.9% vs −2.4% placebo, difference −12.4 points (95% CI −13.4 to −11.5). Trial product estimand −16.9% vs −2.4%. Thresholds: 86.4% reached ≥5%, 69.1% ≥10%, 50.5% ≥15%, 32.0% ≥20%. Absolute −15.3 kg. Discontinued for adverse events 7.0% vs 3.1%. Nausea 44.2% vs 17.4%. Diabetes was an exclusion criterion; mean baseline BMI 37.9, weight 105.3 kg, 74.1% women. Read in full from the author-posted PDF.
  2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. DOI 10.1056/NEJMoa2206038. PMID 35658024. NCT04184622. SURMOUNT-1. 2,539 adults, 72 weeks including 20 weeks of dose escalation, 5, 10 or 15 mg or placebo. Participants with diabetes excluded. Mean baseline weight 104.8 kg, BMI 38.0. Citation and population verified via Europe PMC. This page sources SURMOUNT-1's two estimand figures to reference 3 rather than here, because the company release sets both out explicitly and the abstract does not.
  3. Eli Lilly and Company. SURMOUNT-1 results published in the New England Journal of Medicine. Company release, 4 June 2022. The source for SURMOUNT-1's two estimands side by side. Efficacy estimand 16.0 / 21.4 / 22.5% by dose vs 2.4% placebo. Treatment-regimen estimand 15.0 / 19.5 / 20.9% vs 3.1% placebo. Lilly defines the efficacy estimand as representing "efficacy prior to discontinuation of study drug" and the treatment-regimen estimand as "the estimated average treatment effect regardless of treatment discontinuation." Thresholds at 15 mg, efficacy estimand: 96% ≥5%, 90% ≥10%, 78% ≥15%, 63% ≥20%, 39.7% ≥25%. Discontinued for adverse events 4.3 / 7.1 / 6.2% vs 2.6% placebo. Nausea 31.0% at 15 mg vs 9.5% placebo. A company release rather than the paper, used because it sets out both estimands explicitly where most secondary coverage does not.
  4. Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published online 29 September 2026. DOI 10.1056/NEJMoa2604169. NCT05929066. *TRIUMPH-1. 2,339 adults with obesity and without diabetes, 131 sites in 11 countries, 80 weeks, 4, 9 or 12 mg weekly or placebo. Mean baseline BMI about 40. Treatment-regimen estimand −17.6 / −23.7 / −25.0% vs −3.9% placebo. Discontinued for adverse events 4.1 / 6.5 / 11.2% vs 4.6% placebo. Title and DOI confirmed against two independent bibliographic indexes. Volume and page numbers were not yet assigned when this page was written. The figures above were read through trade coverage of the paper rather than the paper itself, which sits behind a subscription wall, and the discontinuation figures differ from Lilly's May 2026 topline release (see reference 7). *
  5. Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36. DOI 10.1056/NEJMoa2416394. PMID 40353578. NCT05822830. SURMOUNT-5. The only randomized head-to-head trial of any two drugs on this page. 751 adults with obesity and without diabetes, randomized 1:1, 72 weeks, each drug at the maximum tolerated dose: tirzepatide 10 or 15 mg, semaglutide 1.7 or 2.4 mg. Tirzepatide −20.2% (95% CI −21.4 to −19.1) vs semaglutide −13.7% (95% CI −14.9 to −12.6), p<0.001. Waist circumference −18.4 cm vs −13.0 cm. Open-label. Reports least-squares mean percent change and names neither estimand.
  6. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. DOI 10.1056/NEJMoa2301972. The published Phase 2. Cited here for the mechanism rather than the efficacy figures. Heart rate rose with dose, peaking at 24 weeks.
  7. Eli Lilly and Company. TRIUMPH-1 topline results. Company release, 21 May 2026. The source of the widely quoted 28.3%, which is the efficacy estimand at 12 mg, against 2.2% placebo, with 19.0% at 4 mg and 25.9% at 9 mg. Also the source for nausea about 41% at the top dose and dysesthesia 5.1 to 12.5% vs 0.9% placebo. This release gives discontinuation for adverse events as 4.1 / 6.9 / 11.3% vs 4.9% placebo, which the published paper revised to 4.1 / 6.5 / 11.2% vs 4.6%. Where the two disagree this page uses the paper. A company release, not peer reviewed.
  8. Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232. 17,604 adults. 20% relative reduction in major adverse cardiovascular events.
  9. Nicholls SJ, et al. SURPASS-CVOT. N Engl J Med. 2025;393:2409-2420. 13,299 adults with diabetes, tirzepatide against dulaglutide as active comparator rather than placebo.
  10. WEGOVY prescribing information. Novo Nordisk. FDA label. Approved indication, boxed warning for thyroid C-cell tumors, and listed adverse reactions.
  11. ZEPBOUND prescribing information. Eli Lilly. FDA label. As above for tirzepatide.
  12. Manufacturer direct pricing and retail list prices, mid-2026. Self-pay programs in the few hundred dollars per month; retail list prices roughly $1,000 to $1,350 per month. Prices change frequently.
  13. Peptide Decoding vendor price capture, 5 October 2026. *7,762 listings across 158 vendors. Semaglutide 180 listings / 85 vendors, median $8.00 per mg across 124 clean single-vial listings, range $1.00 to $112.79. Tirzepatide 285 / 94, median $4.75 across 226, range $0.07 to $95.00. Retatrutide 345 / 111, median $7.33 across 258, range $1.45 to $76.00. 120 of 158 vendors sell at least one; 71 sell all three; 17 sell retatrutide only. Alias counts from our compound library: 17, 27 and 34. A snapshot. These figures move within days. *
  14. Janvier S, et al. Analytical characterisation of illicit peptide drugs. Talanta. 2018;188:795-807. DOI 10.1016/j.talanta.2018.06.023. Purity of seized peptide products ranged from 5 to 75%. Not a study of these three compounds; cited for what unregulated peptide supply chains deliver in general.
Keep reading