Retatrutide

In a phase 3 trial of 2339 adults with obesity and without diabetes, body weight fell more with retatrutide than with placebo over 80 weeks.

TRIUMPH-1 randomised 2339 adults with obesity and without diabetes to retatrutide at 4 mg, 9 mg or 12 mg, or to placebo, for 80 weeks. Under the treatment-regimen estimand, which the paper equates with intention-to-treat, mean body weight changed by -17.6%, -23.7% and -25.0% in the three arms against -3.9% with placebo, differences of -19.8 and -21.0 percentage points for the 9 mg and 12 mg arms. An earlier phase 2 trial in 338 adults with a BMI of 30 or higher, or 27 or higher with a weight-related condition, and without diabetes, reported -24.2% in its 12 mg arm against -2.1% with placebo at 48 weeks, in the same direction.

Tested in humans under randomised, controlled conditions.

• The figures come from the published abstracts only. The full texts were not available when this page was written.
• Both trials were funded by Eli Lilly, the developer.
• The results describe Lilly's investigational product given under trial conditions, not any product sold outside a trial.
• The TRIUMPH-1 abstract states the difference from placebo only for the 9 mg and 12 mg arms, and gives no adverse event frequencies or discontinuation rate.
• The phase 2 figures are least-squares means and that abstract names no estimand, so they are not directly comparable with the phase 3 figures.
• 80 weeks is the longest treatment period published. What happens to weight beyond it is not known from these trials.

PMID 42814954PMID 37366315

In a phase 3 trial of 1152 adults with type 2 diabetes and a BMI of 27 or higher, body weight fell more with retatrutide than with placebo over 80 weeks.

TRIUMPH-2 randomised 1152 adults with type 2 diabetes and a BMI of 27 or higher, at 92 centres in eight countries, to retatrutide at 4 mg, 9 mg or 12 mg, or to placebo. Under the treatment-regimen estimand, mean body weight at week 80 changed by -11.9% with 4 mg, -16.8% with 9 mg and -18.8% with 12 mg, against -5.1% with placebo. The estimated differences from placebo were -6.9, -11.8 and -13.8 percentage points.

Tested in humans under randomised, controlled conditions.

• The figures come from the published abstract only. The full text was not available when this page was written.
• The trial was funded by Eli Lilly, the developer.
• The results describe Lilly's investigational product given under trial conditions, not any product sold outside a trial.
• 965 of the 1152 participants (84%) completed the study drug, and missing data were imputed.
• The abstract gives no efficacy-estimand result and no HbA1c figure; it says only that the drug was associated with improvements in glycaemic control.

PMID 42810372

In a phase 3 trial of 537 adults with type 2 diabetes managed by diet and exercise alone, HbA1c fell more with retatrutide than with placebo over 40 weeks.

TRANSCEND-T2D-1 randomised 537 adults whose type 2 diabetes was inadequately controlled by diet and exercise alone, with glycated haemoglobin (HbA1c) between 7.0% and 9.5%, at 48 sites in the USA, Mexico and India. Under the treatment-regimen estimand, mean HbA1c changed by -1.69% with 4 mg, -1.86% with 9 mg and -1.94% with 12 mg against -0.81% with placebo, differences of -0.88, -1.04 and -1.12 percentage points. An earlier phase 2 trial randomised 281 adults with type 2 diabetes treated with diet and exercise alone or with a stable dose of metformin; among the 275 in its efficacy analysis, HbA1c changed by -2.02% at 24 weeks in the 12 mg arm against -0.01% with placebo and -1.41% with dulaglutide 1.5 mg.

Tested in humans under randomised, controlled conditions.

• The figures come from the published abstracts only. The full texts were not available when this page was written.
• Both trials were funded by Eli Lilly, the developer.
• The results describe Lilly's investigational product given under trial conditions, not any product sold outside a trial.
• Participants in the phase 3 trial had had diabetes for a mean of 2.5 years and were managing it with diet and exercise alone, so the result does not directly describe people already taking other diabetes medicines.
• HbA1c and body weight were the stated endpoints. The abstract reports no outcomes for diabetes complications.
• The phase 2 trial also enrolled people taking metformin, so its population is wider than the phase 3 trial's.
• The phase 2 figures are least-squares means and that abstract names no estimand.

PMID 42250575PMID 37385280

Within TRIUMPH-1, knee osteoarthritis pain and the apnoea-hypopnoea index in obstructive sleep apnoea both fell more with retatrutide than with placebo in subgroups of participants with those conditions.

In the 574 participants with knee osteoarthritis, WOMAC pain, on a scale the abstract describes as ranging from 1 to 10, changed by -3.2, -3.5 and -3.6 points in the 4 mg, 9 mg and 12 mg arms against -1.9 with placebo under the hybrid estimand the paper applied (differences -1.6 and -1.8 for 9 mg and 12 mg), and by -3.4, -3.9 and -4.1 against -2.5 under intention-to-treat (differences -1.4 and -1.6). In the 243 participants with obstructive sleep apnoea, the apnoea-hypopnoea index, counted in events per hour, changed by -22.8, -34.3 and -32.1 against -9.6 with placebo under intention-to-treat (differences -24.7 and -22.5 for 9 mg and 12 mg). Under the hybrid estimand the stated differences were -24.4 and -21.9, against a placebo change of -9.9.

Tested in humans under randomised, controlled conditions.

• The figures come from the published abstract only. The full text was not available when this page was written.
• The trial was funded by Eli Lilly, the developer.
• The results describe Lilly's investigational product given under trial conditions, not any product sold outside a trial.
• These were pre-specified primary outcomes, but in subgroups of 574 and 243 participants within one obesity trial. TRIUMPH-4, the trial built around knee osteoarthritis, has not been published.
• The PubMed abstract prints the 12 mg hybrid-estimand sleep apnoea value without its minus sign, so the per-arm sleep apnoea figures given here are the intention-to-treat ones.
• The abstract does not state at what point in the 80 weeks these two endpoints were measured.
• The abstract does not state the 4 mg arm's differences from placebo for either measure.

PMID 42814954

In a phase 2 substudy of 98 participants with MASLD, liver fat fell more with retatrutide than with placebo at 24 weeks.

Participants in the phase 2 obesity trial who had MASLD (metabolic dysfunction-associated steatotic liver disease) and liver fat of at least 10% were randomised, 98 in all, to retatrutide at 1, 4, 8 or 12 mg, or to placebo. The mean relative change from baseline in liver fat at 24 weeks was -42.9%, -57.0%, -81.4% and -82.4% in the four arms against +0.3% with placebo. Liver fat fell below 5% in 86% of the 12 mg arm and in 0% of the placebo arm.

Tested in humans under randomised, controlled conditions.

• Liver fat is a surrogate measure. The study reports nothing about fibrosis, liver histology or clinical liver outcomes.
• 98 participants over 24 weeks, split across five arms.
• The figures come from the published abstract only, which names no estimand.
• The trial was funded by Eli Lilly, the developer.
• The results describe Lilly's investigational product given under trial conditions, not any product sold outside a trial.

PMID 38858523