Presented by PAY FIT
From phase 1 to the TRIUMPH programme: how the evidence for a peptide is built
What each phase of a clinical trial answers, and how retatrutide moved from phase 1 and phase 2 into the phase 3 TRIUMPH programme, running since 2023.
The evidence for a peptide is built in stages, and each stage looks at something different: phase 1 observes tolerability and how the molecule behaves in the body, in a small number of volunteers; phase 2 explores what happens in larger groups, with hundreds of participants; and phase 3 confirms what was observed in thousands of people. Retatrutide has been through the first two, with results published in 2022 and 2023, and is now part of the phase 3 TRIUMPH programme, running since 2023.
Before any volunteer: the laboratory work
Before a molecule reaches a person, it goes through the preclinical stage. It is designed, tested in the laboratory and in animal models, and a formulation is worked out so that it stays stable: concentration, excipients and storage conditions. For retatrutide, the design aimed at a molecule able to act on three receptors (GLP‑1, GIP and glucagon). This stage produces no results in people, but without it there is no phase 1.
Phase 1 and phase 2: from tolerability to larger groups
Phase 1. A small group takes part, usually a few dozen volunteers. The study looks at tolerability, meaning how the body responds to the molecule, and at its behaviour in the body: how it is absorbed, distributed and eliminated, known as pharmacokinetics. For retatrutide, the results of this phase were published in 2022.
Phase 2. The study widens to hundreds of participants, split into groups that are compared with one another. It explores what happens in a larger set of people and gathers data that shape the design of the next stage. The retatrutide phase 2 study ran for 48 weeks and was published in 2023 in a widely read medical journal (New England Journal of Medicine). As an example of what a phase 2 reports: in that study, in a specific population, the average for the groups that received the molecule showed a larger reduction in body weight than in the comparison group, which received a placebo. It is a group average and does not predict the result for any one person.
Phase 3: confirming it in thousands of people
Phase 3 aims to confirm what was seen earlier in a much larger and more varied group, followed for longer, and to watch adverse events more closely. The TRIUMPH programme has been running since 2023 and brings together several trials in different populations, for example people with obesity and with other conditions linked to it. Each trial has its own design, duration and main question. Some have already reported data, while others are still under way.
The phases side by side
| Stage | Who takes part | Main question | For retatrutide |
|---|---|---|---|
| Preclinical | Laboratory and animal models | Is the molecule stable and does it act as designed? | Triple-action molecule |
| Phase 1 | A small number of volunteers | How does the body tolerate it? How does it process it? | Published in 2022 |
| Phase 2 | Hundreds of participants | What is observed in larger groups compared with one another? | 48-week study, published in 2023 |
| Phase 3 | Thousands of participants | Do the findings hold in a large, varied population? | TRIUMPH programme, running since 2023 |
How to read a published result
With these phases in mind, five questions help in reading any study:
- Which phase is it? A phase 2 points the way; a phase 3 confirms with a larger sample.
- Who took part? The results apply to that population, not to everyone.
- How long did it last? Four weeks does not say the same as eighty.
- What was it compared with? A comparison group makes it possible to separate the effect of the molecule from other factors.
- Is it an average or an individual case? The figures in a study are group averages and promise nobody a result.
To understand how the molecule acts, see the article on the three receptors; for the trial data, the summary of results.
For information only; it does not replace the advice of a healthcare professional.
