Retatrutide Clinical Trials and Results: What We Know So Far
Written by Dan Cripe, RN, BSN & Marcia Cripe, RN
Current evidence review: August 27, 2026
Retatrutide has moved well beyond being an interesting early-stage obesity drug.
When its Phase 2 obesity results were published in 2023, the headline was the magnitude of weight loss: participants receiving the highest dose lost an average of 24.2% of their body weight at 48 weeks, and the weight-loss curve had not yet clearly plateaued. At the time, those results made retatrutide one of the most closely watched medications in obesity research.
Three years later, the picture is substantially different.
We now have positive Phase 3 results in people with obesity without diabetes, obesity with type 2 diabetes, severe obesity with established cardiovascular disease, knee osteoarthritis and obstructive sleep apnea. In the pivotal TRIUMPH-1 obesity trial, the highest-dose group lost an average of 28.3% of body weight at 80 weeks. In a study extension among participants with a baseline BMI of at least 35, average weight loss reached 30.3% at 104 weeks.
That is no longer a Phase 2 signal waiting to be confirmed.
But retatrutide is also not an approved obesity medication.
It remains investigational. Lilly says it now has the clinical data package to support global regulatory submissions and plans to submit a Biologics License Application to the FDA in the first quarter of 2027. Detailed peer-reviewed publication is also still pending for some of the newest Phase 3 results.
That distinction—between what the trials have now demonstrated and what has not happened yet—is where the retatrutide story stands today.
What Retatrutide Is
Retatrutide is a once-weekly investigational peptide developed by Eli Lilly that activates three hormone receptors:
GIP — glucose-dependent insulinotropic polypeptide
GLP-1 — glucagon-like peptide-1
Glucagon
That third receptor is what most obviously distinguishes retatrutide from tirzepatide, which activates GIP and GLP-1 receptors but not the glucagon receptor.
Calling retatrutide a “triple agonist” is therefore not marketing shorthand. It describes its pharmacology.
The original Phase 2 publication also showed that retatrutide does not activate those three receptors equally relative to their natural human ligands. In preclinical receptor assays described in the paper, retatrutide was substantially more potent at the human GIP receptor relative to native GIP, while its relative activity at the GLP-1 and glucagon receptors was lower than their native ligands. Retatrutide has an approximately six-day half-life, allowing once-weekly administration.
What remains much harder to answer is exactly how much each component contributes to the clinical results.
GLP-1 and GIP signaling can affect appetite, food intake and metabolic regulation. Adding glucagon-receptor activity introduces another potential influence on energy balance and substrate metabolism. The hypothesis behind combining these pathways is that glucagon-receptor agonism may add effects on energy expenditure or metabolism to the appetite and metabolic effects of incretin signaling.
That is a plausible mechanistic explanation.
It is not the same as proving that retatrutide produces greater weight loss specifically because glucagon receptor activation increases energy expenditure in humans.
That distinction remains important as the drug moves closer to regulatory review.
What Phase 2 Actually Established
The Phase 2 obesity trial randomized 338 adults with obesity, or overweight plus at least one weight-related condition, who did not have diabetes.
Participants received placebo or various retatrutide dosing regimens for 48 weeks.
The dose-response relationship was striking.
At 48 weeks, average weight change was:
At 12 mg, 83% of participants lost at least 15% of their body weight, and 26% lost at least 30%. Weight loss in the higher-dose groups had not clearly reached a plateau at week 48.
The trial also established an important safety signal that has continued to matter during development: gastrointestinal adverse events were common, dose-related and predominantly mild to moderate. Starting at a lower dose reduced some of that burden. Dose-dependent increases in heart rate were also observed, peaking around 24 weeks and declining afterward.
Phase 2 therefore established more than “retatrutide causes a lot of weight loss.”
It established a strong dose-response signal, identified tolerability issues that would influence dose escalation, and provided enough efficacy and safety evidence to justify a large Phase 3 development program.
What it could not establish was whether those results would hold up in much larger and more clinically varied populations.
That is what Phase 3 needed to answer.
The Phase 3 Picture Has Changed Dramatically
The first major Phase 3 breakthrough came from a population that was not simply “people with obesity.”
It came from people with obesity and knee osteoarthritis.
TRIUMPH-4: Obesity and Knee Osteoarthritis
In December 2025, Lilly announced positive topline results from TRIUMPH-4, a Phase 3 trial involving adults with obesity or overweight and knee osteoarthritis without diabetes.
At 68 weeks, participants receiving 12 mg retatrutide lost an average of 28.7% of their body weight, compared with 2.1% with placebo.
But weight was only part of the trial.
Retatrutide also produced substantial reductions in knee osteoarthritis pain. Lilly reported reductions in WOMAC pain scores of up to 75.8%, along with improvements in physical function; more than one in eight retatrutide-treated participants were reported to be free of knee pain at the end of the trial.
Those findings expanded the retatrutide story beyond how many pounds participants could lose.
They also raised a more difficult question that the headline numbers alone cannot answer: how much of the improvement in knee pain results from weight loss itself, how much may reflect other metabolic or inflammatory effects, and whether those effects can be separated clinically.
That is an example of something a Living Report should keep open rather than resolving prematurely.
TRIUMPH-1: The Pivotal Obesity Trial
The most important obesity efficacy result arrived in May 2026.
TRIUMPH-1 studied adults with obesity or overweight plus at least one weight-related comorbidity who did not have diabetes. ClinicalTrials.gov identifies the study as NCT05929066.
At 80 weeks, average weight loss reached:
19.0% with 4 mg
and
28.3% with 12 mg
in Lilly’s reported efficacy results.
Participants in the 12-mg group lost an average of 70.3 pounds, and 45.3% achieved at least 30% weight loss.
The trial also included an extension for participants whose baseline BMI was at least 35.
At 104 weeks, those participants continued losing weight, reaching average reductions of up to 30.3%, or approximately 85 pounds.
That extension matters because one of the biggest unanswered questions after Phase 2 was whether the extraordinary 48-week weight-loss curve simply reflected a trial that ended before participants reached their eventual plateau.
TRIUMPH-1 now shows that substantial additional weight loss can continue beyond 48 weeks in at least some populations.
It does not establish that everyone taking retatrutide would lose 30% of body weight, nor that 30% represents the drug’s universal plateau.
It tells us that the weight-loss effect can extend well beyond the first year and that the upper end of average efficacy observed in Phase 3 is considerably greater than the Phase 2 data alone had established.
Retatrutide Also Improved Obstructive Sleep Apnea
Additional TRIUMPH-1 data presented in June 2026 included participants with moderate-to-severe obstructive sleep apnea.
Lilly reported reductions in apnea-hypopnea index of up to 36.1 events per hour, corresponding to a 60.6% reduction at the highest reported result.
Again, the clinical interpretation matters.
Obesity is a major contributor to obstructive sleep apnea, so substantial weight reduction would be expected to improve disease severity in many patients. These findings establish improvement during retatrutide treatment; they do not by themselves tell us that retatrutide has a unique anti-OSA mechanism independent of its effects on weight.
That distinction will become increasingly important if retatrutide eventually seeks or receives indications beyond obesity alone.
What We Now Know In People With Type 2 Diabetes
Weight-loss medications generally produce somewhat smaller average reductions in body weight in populations with type 2 diabetes than in populations without diabetes.
TRIUMPH-2 tested retatrutide in adults with obesity or overweight and type 2 diabetes.
Lilly reported July 2026 topline results showing average weight loss at 80 weeks of:
12.7% with 4 mg
19.1% with 9 mg
20.8% with 12 mg
The highest-dose group lost an average of 49.6 pounds.
Retatrutide also reduced A1C by up to an average of 1.6 percentage points.
That result matters for two reasons.
First, it confirms substantial weight-loss efficacy in a population where achieving the same magnitude of loss is generally more difficult.
Second, it confirms that the triple-agonist strategy can produce clinically meaningful glycemic improvement while producing substantial weight reduction.
The detailed TRIUMPH-2 results have not yet completed the same full peer-reviewed publication cycle as the older Phase 2 data, so the topline findings should not be treated as though every subgroup, adverse-event analysis and secondary endpoint has already undergone complete public scrutiny.
That is not a reason to dismiss the results.
It is a reason to describe their current evidence status correctly.
TRIUMPH-3 Expanded The Population Again
TRIUMPH-3 studied adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes. ClinicalTrials.gov lists body-weight change at week 80 as a primary outcome.
Lilly’s July 2026 topline announcement reported average weight loss of up to 22.6%, corresponding to approximately 55.8 pounds.
This population is clinically important because these participants already had established cardiovascular disease and severe obesity.
But TRIUMPH-3 should not be confused with a cardiovascular outcomes trial demonstrating that retatrutide prevents heart attacks, strokes or cardiovascular death.
A trial can enroll people with cardiovascular disease without being designed or powered to establish cardiovascular event reduction.
That distinction will matter enormously as retatrutide moves toward regulatory review and comparisons with medications that already have cardiovascular outcomes data.
So How Much Weight Loss Does Retatrutide Produce?
There is no single retatrutide percentage.
The result depends on:
- dose
- treatment duration
- diabetes status
- baseline population
- trial design
- treatment adherence
- how the statistical estimand handles treatment discontinuation and other events
But we can now describe the overall evidence much more confidently than we could after Phase 2.
In adults with obesity without diabetes, Phase 3 results have shown average weight reductions approaching or exceeding the high-20% range at the highest studied doses and durations.
In selected participants with BMI of at least 35 who continued into the TRIUMPH-1 extension, average loss reached approximately 30% at two years.
In adults with type 2 diabetes, average weight loss was lower but still reached approximately 21% at the highest dose in TRIUMPH-2.
Those are extraordinary pharmacologic weight-loss results.
They should be described as such.
They should not be converted into the claim that retatrutide produces “30% weight loss” as though that is the expected outcome for every person who eventually takes it.
What We Know About Safety So Far
The broad adverse-event pattern remains familiar for an incretin-based medication.
Across trials, gastrointestinal adverse events—including nausea, diarrhea, vomiting and constipation—have been prominent. Phase 2 demonstrated that gastrointestinal events were dose-related and that a lower starting dose improved tolerability.
The Phase 3 program continues to provide a much larger safety database, but complete regulatory safety labeling does not yet exist because retatrutide has not been approved.
That distinction is important.
For an approved medication, we can point to a finalized prescribing label that synthesizes regulatory evaluation of contraindications, warnings, precautions and adverse reactions.
For retatrutide, we are still working from clinical-trial evidence and sponsor-reported Phase 3 results.
There is enough evidence to characterize common trial tolerability patterns.
There is not yet an FDA-approved retatrutide label from which to describe its final clinical safety profile.
Retatrutide Is Still Investigational
This is probably the most important fact to keep current in this article.
As of August 27, 2026, retatrutide has not been approved by the FDA or any other regulatory agency. Lilly explicitly states that products being sold outside its clinical trials as “retatrutide” are not approved retatrutide products and may contain incorrect quantities, contaminants or entirely different ingredients.
The existence of retatrutide sold through peptide websites or compounding channels does not change the drug’s regulatory status.
Clinical-trial retatrutide and an online vial labeled “retatrutide” are not scientifically interchangeable evidence.
Lilly says it plans to submit retatrutide to the FDA in the first quarter of 2027.
That means the next major phase of the story is increasingly regulatory rather than simply experimental.
The Tirzepatide Comparison Is Still Coming
One of the most anticipated retatrutide studies is TRIUMPH-5.
This trial directly compares retatrutide with tirzepatide in approximately 800 adults with obesity.
Unlike indirect comparisons between separate clinical trials, TRIUMPH-5 is designed to test the two drugs within the same randomized Phase 3 study.
Lilly currently lists the trial as having completed enrollment, with study completion expected in December 2026.
Until those results are available, statements that retatrutide is definitively “better than tirzepatide” remain premature.
Cross-trial comparisons can be suggestive.
They are not substitutes for a head-to-head trial.
TRIUMPH-5 is therefore one of the most important remaining evidence events to watch.
Development Has Not Stopped With The First Regulatory Package
Even as Lilly prepares for regulatory submissions, retatrutide’s clinical development is continuing.
For example, TRIUMPH-9 is examining different dose-escalation approaches in adults with obesity or overweight without type 2 diabetes. Lilly lists the Phase 3 study as running through 2028.
That matters because efficacy is only one part of optimizing a medication.
The Phase 2 program already showed that starting dose and escalation affected gastrointestinal tolerability. Later trials can help determine whether different titration strategies preserve efficacy while making treatment easier to tolerate.
The retatrutide evidence base therefore will not become static if the medication receives approval.
Approval would mark a major transition.
It would not mark the end of the research.
What We Know Now
As of August 2026, several conclusions are considerably stronger than they were when retatrutide first attracted attention.
Retatrutide produces substantial weight loss.
That is no longer merely a Phase 2 observation. Multiple Phase 3 trials now support it.
The magnitude of weight loss can be very large.
In TRIUMPH-1, average weight loss reached 28.3% at 80 weeks with 12 mg, and selected participants continuing to 104 weeks reached an average of 30.3%.
Retatrutide works in clinically different obesity populations.
Positive Phase 3 results now include people without diabetes, people with type 2 diabetes, people with severe obesity and cardiovascular disease, and people with obesity-related knee osteoarthritis or obstructive sleep apnea.
Gastrointestinal tolerability remains important.
That has been visible since Phase 2 and remains relevant as dosing strategies are refined.
Retatrutide is not approved.
No amount of promising trial data changes that until regulatory review occurs.
And several major questions remain open.
We do not yet have the TRIUMPH-5 head-to-head result against tirzepatide.
We do not yet have a final FDA regulatory decision or prescribing label.
Some recent Phase 3 findings remain topline or conference data rather than complete peer-reviewed publications.
Long-term real-world effectiveness and safety cannot be known before the drug is actually used broadly outside clinical trials.
And we still do not completely understand how the three receptor components contribute individually to the magnitude and character of retatrutide’s effects.
Those aren’t small footnotes.
They are the next part of the story.
Retatrutide Evidence & Development Timeline
June 2023 — Phase 2 Obesity Results Published
The Phase 2 trial reported average weight loss of up to 24.2% at 48 weeks with 12 mg retatrutide. Participants in the higher-dose groups were still losing weight when treatment ended. The study established the initial efficacy signal, dose-response relationship and important gastrointestinal tolerability findings.
December 2025 — TRIUMPH-4 Becomes The First Positive Phase 3 Trial
Lilly announced that participants receiving 12 mg retatrutide lost an average of 28.7% at 68 weeks in a population with obesity and knee osteoarthritis. Substantial improvements in knee pain and physical function were also reported.
May 2026 — TRIUMPH-1 Confirms Phase 3 Obesity Efficacy
Lilly reported average weight loss of 28.3% at 80 weeks with 12 mg in adults with obesity or overweight without diabetes. Participants with baseline BMI of at least 35 who continued to 104 weeks reached average weight loss of 30.3%.
June 2026 — Additional TRIUMPH-1 Results Expand The Picture
Results presented at the ADA Scientific Sessions included substantial improvements in knee osteoarthritis pain and obstructive sleep apnea severity in studied subsets.
July 2026 — TRIUMPH-2 Reports Results In Type 2 Diabetes
Adults with obesity or overweight and type 2 diabetes lost up to an average of 20.8% at 80 weeks, with A1C reductions of up to 1.6 percentage points.
July 2026 — TRIUMPH-3 Reports Results In Severe Obesity And Cardiovascular Disease
Lilly reported average weight loss of up to 22.6% at 80 weeks in adults with severe obesity and established cardiovascular disease, with or without type 2 diabetes.
July 2026 — Lilly Announces Planned Regulatory Submission
With multiple positive Phase 3 studies completed, Lilly said it plans to submit retatrutide to the FDA in Q1 2027.
Expected December 2026 — TRIUMPH-5 Completion
The Phase 3 head-to-head trial comparing retatrutide with tirzepatide is expected to complete in December 2026.
What We’re Watching Next
The next update to this report should not happen simply because another retatrutide article appears in the news.
It should happen when the evidence changes.
The most important developments currently ahead are the TRIUMPH-5 retatrutide-versus-tirzepatide results, full publication of newer Phase 3 datasets, Lilly’s planned regulatory submission, FDA review and any additional safety or dosing evidence that materially changes what is known about the drug.
When those events occur, the current-state sections of this article should change where necessary.
The timeline should preserve what happened and when.
That way, this report does not repeatedly start the retatrutide story over.
It keeps telling it as the evidence develops.
Sources
1. Jastreboff AM, Kaplan LM, Frías JP, et al. Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. 2023;389:514–526. doi:10.1056/NEJMoa2301972. DOI
https://doi.org/10.1056/NEJMoa2301972
2. Eli Lilly and Company. TRIUMPH-4 Phase 3 topline results. December 11, 2025. Eli Lilly and Company
3. Eli Lilly and Company. TRIUMPH-1 Phase 3 topline results. May 21, 2026. Eli Lilly and Company
4. Eli Lilly and Company. Additional TRIUMPH-1 and retatrutide Phase 3 results presented at the American Diabetes Association Scientific Sessions. June 6, 2026. Eli Lilly and Company
5. Eli Lilly and Company. TRIUMPH-2 and TRIUMPH-3 Phase 3 topline results. July 23, 2026. Eli Lilly and Company
6. ClinicalTrials.gov. TRIUMPH-1: A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight. NCT05929066. ClinicalTrials.gov
https://clinicaltrials.gov/study/NCT05929066
7. ClinicalTrials.gov. TRIUMPH-2: A Study of Retatrutide (LY3437943) in Participants With Type 2 Diabetes Mellitus Who Have Obesity or Overweight. NCT05929079. ClinicalTrials.gov
https://clinicaltrials.gov/study/NCT05929079
8. ClinicalTrials.gov. TRIUMPH-3: A Study of Retatrutide (LY3437943) in Participants With Obesity and Cardiovascular Disease. NCT05882045. ClinicalTrials.gov
https://clinicaltrials.gov/study/NCT05882045
9. Eli Lilly and Company. TRIUMPH-5: A Study of Retatrutide (LY3437943) Compared With Tirzepatide (LY3298176) in Adults Who Have Obesity. NCT06662383. Lilly Trials
https://trials.lilly.com/en-US/trial/549215
For this one, I would actually also include the ClinicalTrials.gov record because it is the independent federal trial registry:
https://clinicaltrials.gov/study/NCT06662383
10. Eli Lilly and Company. What to Know About Retatrutide: An Investigational Triple Hormone Receptor Agonist.Current regulatory and development status. Last updated July 2026. Lilly
https://www.lilly.com/news/stories/what-to-know-about-retatrutide
Last evidence review: August 27, 2026
Status: Updated when material new evidence or regulatory developments emerge.