The strong phase 2 results needed confirmation in large, carefully designed phase 3 trials — and the TRIUMPH programme (begun in 2023, with over 5,800 participants in the obesity arm and, together with the cardiovascular trial, tens of thousands) has started to deliver them. The first results not only confirmed but in places exceeded the earlier data. This is the stage at which a “promising investigational drug” becomes a “candidate for approval”.
What the TRIUMPH programme is
TRIUMPH is one of the broadest phase 3 programmes for a metabolic drug in history. It consists of a whole family of parallel trials testing retatrutide in many different patient groups at once — from “pure” obesity, through type 2 diabetes (some trials are named TRANSCEND), to the conditions that accompany obesity. That scale allows it to demonstrate not just weight loss but real health benefits in specific patient groups.
TRIUMPH-1 — the pivotal obesity trial
TRIUMPH-1 is the central trial of the whole programme — most probably the basis of the approval application (to the US FDA among others) in obesity. It enrolled 2,339 participants with obesity or overweight who also had at least one weight-related complication.
After 80 weeks the average weight loss (using the approach that accounts for everyone enrolled) was:
- 4 mg: 17.6%
- 9 mg: 23.7%
- 12 mg: 25.0%
- placebo: 3.9%
In another analysis (covering those who continued treatment as planned) the 12 mg dose gave an average of about 28.3% weight loss — roughly 32 kg, and 45.3% of participants lost at least 30% of their body weight. In some subgroups and with longer follow-up the figures reached about 30%. Those two numbers (25% and 28.3%) are the same result counted by two standard statistical methods, not a contradiction.
This is a level previously associated almost exclusively with weight-loss surgery — achieved here by drug treatment alone. Most importantly: phase 3 confirmed the phase 2 signal in a large, independent group.
TRIUMPH-4 — obesity and knee osteoarthritis
The first successful, publicly announced phase 3 result (December 2025) concerned adults with obesity and knee osteoarthritis — a common, painful complication of excess weight (the cartilage in the joint gradually wears away, causing pain). Participants lost up to 28.7% of body weight (an average of about 32 kg) after 68 weeks, and 58.6% achieved at least 25% weight loss. What matters most, though, is that this came with clear relief of joint pain — a concrete health benefit going beyond the number on the scale. It shows that retatrutide can genuinely improve quality of life, not just test results.
Type 2 diabetes — TRANSCEND-T2D-1
Efficacy and safety in type 2 diabetes were confirmed by the phase 3 trial TRANSCEND-T2D-1 (The Lancet, 2026). In patients with diabetes, retatrutide combined better blood-sugar control with marked weight loss — two benefits usually hard to obtain together in this group, and which together strike at the mechanism of the disease itself.
The decisive test — the cardiovascular trial
The most important test for any metabolic drug is the so-called hard endpoints: whether the drug genuinely reduces heart attacks, strokes, deaths and decline in kidney function, rather than merely improving test results. Retatrutide is being assessed in a large cardiovascular and renal trial of the order of 10,000 participants (including the registry entry NCT05882045 in people with obesity and heart disease). A good result in such a trial is the “gold standard” that determines a drug's place in official clinical guidelines.
The structure of the programme — four main trials
The core of the TRIUMPH programme (described in detail in the design paper by Giblin et al., Diabetes, Obesity and Metabolism, 2026) consists of four large phase 3 trials of a once-weekly subcutaneous injection against placebo, combined with a healthy diet and exercise:
- TRIUMPH-1 — obesity/overweight with complications (the pivotal trial, described above).
- TRIUMPH-2 — obesity/overweight coexisting with type 2 diabetes.
- TRIUMPH-3 — obesity/overweight with established cardiovascular disease.
- TRIUMPH-4 — a separate trial in knee osteoarthritis (described above).
TRIUMPH-1 and TRIUMPH-2 have additional embedded arms covering sleep apnoea (pauses in breathing during sleep) and osteoarthritis — so a single trial assesses several complications of obesity at once.
Other applications under way
Beyond the four main trials, seven further phase 3 trials are due to report in 2026 and later. They cover, among others:
- Sleep apnoea — a common, dangerous complication of obesity (pauses in breathing during sleep).
- Fatty liver disease (MASLD/MASH) — where phase 2 produced exceptional results.
- Chronic low back pain associated with excess body weight.
- Cardiovascular and renal benefits — the large trial testing the real effect on health.
The scale of the results in context
To appreciate the order of magnitude — an indicative comparison of maximum weight loss (different trials and different groups of people):
- Semaglutide 2.4 mg: about 15%
- Tirzepatide 15 mg: about 21%
- Retatrutide (phase 3): about 25–30%
- Weight-loss surgery: usually about 25–35%
Retatrutide is the first drug to come genuinely close to figures previously reserved for surgery — and without an operation.
Limitations and open questions
An honest picture requires showing the limits. First — durability of the effect: as across this drug class, part of the lost weight usually returns after stopping, which means treatment is long-term. Second — muscle mass: with weight loss on this scale, some of it is tissue other than fat, and the glucagon pathway could in theory intensify that; full body-composition studies from phase 3 will settle the question. Third — gastrointestinal tolerability and the need for slow dose escalation. Fourth — availability and cost: drugs of this class are expensive, and demand sometimes exceeds supply. None of this negates the results, but it shows that retatrutide is not a “magic pill” but a powerful tool requiring medical supervision.
The road to approval
Further results from the TRIUMPH/TRANSCEND programme are arriving in 2026 and later, covering more and more applications. Approval will be decided by the regulators (the FDA in the USA and the EMA in Europe among them) on the basis of the full set of efficacy and safety data — with particular weight given to the cardiovascular trial. Only a positive regulatory decision will turn retatrutide from an “investigational drug” into an available therapy.
Status and what comes next
Accuracy is required: as of 2026 retatrutide remains an investigational drug, not yet approved for therapeutic use. Further phase 3 results and the cardiovascular trial will form the basis of the approval applications. The agreement between phase 2 and phase 3 results is strong enough, however, that retatrutide is today regarded as one of the most promising metabolic drugs in development.
Why this matters
The mechanistic background — why acting on three pathways is so powerful — is described in our article on how retatrutide works, and the earlier data that launched this programme in the piece on the phase 2 trials. The broader context of the whole drug class is in GLP-1, GIP, glucagon — metabolic peptides in research.
Sources
- Eli Lilly (2026), press release — the pivotal phase 3 obesity trial (TRIUMPH-1) — investor.lilly.com
- Eli Lilly (2025), press release — TRIUMPH-4 (obesity and osteoarthritis) — investor.lilly.com
- Phase III retatrutide study demonstrates 30% weight loss, The Pharmaceutical Journal — pharmaceutical-journal.com
- TRANSCEND-T2D-1 (2026), phase 3 in type 2 diabetes, The Lancet — thelancet.com
- Giblin et al. (2026), Retatrutide for the treatment of obesity, obstructive sleep apnea and knee osteoarthritis: rationale and design of the TRIUMPH registrational clinical trials, Diabetes, Obesity and Metabolism — dom-pubs.onlinelibrary.wiley.com
- A discussion of the TRIUMPH-1 results, AJMC — ajmc.com
- The cardiovascular outcomes trial — ClinicalTrials.gov NCT05882045
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.
