Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity
Authors' conclusion
In adults with obesity, retatrutide resulted in significant weight reduction, reduced pain in participants with knee osteoarthritis, and reduced apnea-hypopnea events in participants with obstructive sleep apnea.
Study context
- Population
- Adults with obesity without diabetes; subgroups with knee OA and obstructive sleep apnearandomised · subgroups with knee OA 574 · obstructive sleep apnea 243
- Participants
- 2,339 adults
- Comparison
- Once-weekly subcutaneous retatrutide vs placebo for 80 weeks
- Primary endpoint
- Primary outcomes (9 mg and 12 mg each vs placebo): % change in body weight; change in WOMAC pain score (1–10, higher worse) in knee OA subgroup; change in apnea-hypopnea index in obstructive sleep apnea subgroup
- Follow-up
- 80 weeks
Methodological detailsphase 3, double-blind, placebo-controlled
- Phase 3
- Double-blind
- Placebo-controlled
Primary result
As reported in the abstract
Mean % change in body weight
Difference
−19.8 percentage points
P < 0.001
Retatrutide 9 mg
Difference
−21.0 percentage points
P < 0.001
Retatrutide 12 mg
Retatrutide 4 mg
−17.6
mean · %
Retatrutide 9 mg
−23.7
mean · %
Retatrutide 12 mg
−25.0
mean · %
Placebo
−3.9
mean · %
Further findings
| Outcome | Retatrutide 4 mgpoints | Retatrutide 9 mgpoints | Retatrutide 12 mgpoints | Placebo | Estimate | P value |
|---|---|---|---|---|---|---|
| Co-primary: change in WOMAC pain score (1–10, higher worse), knee OA subgroup (n=574), hybrid estimand · 80 weeksRetatrutide 9 mg vs Placebo · hybrid-treatment estimand | −3.2 | −3.5 | −3.6 | −1.9 points | difference −1.6 points | P < 0.001 |
| Co-primary: change in WOMAC pain score (1–10, higher worse), knee OA subgroup (n=574), hybrid estimand · 80 weeksRetatrutide 12 mg vs Placebo · hybrid-treatment estimand | difference −1.8 points | P < 0.001 | ||||
| Co-primary: change in WOMAC pain score, knee OA subgroup, ITT estimand · 80 weeksRetatrutide 9 mg vs Placebo · ITT estimand | −3.4 | −3.9 | −4.1 | −2.5 points | difference −1.4 points | P < 0.001 |
| Co-primary: change in WOMAC pain score, knee OA subgroup, ITT estimand · 80 weeksRetatrutide 12 mg vs Placebo · ITT estimand | difference −1.6 points | P < 0.001 | ||||
| Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup (n=243), hybrid-treatment estimand · 80 weeksRetatrutide 9 mg vs Placebo · hybrid-treatment estimand | — not stated in the abstract | — not stated in the abstract | — not stated in the abstract | −9.9 events per hour | difference −24.4 | P < 0.001 |
| Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup (n=243), hybrid-treatment estimand · 80 weeksRetatrutide 12 mg vs Placebo · hybrid-treatment estimand | difference −21.9 | P < 0.001 | ||||
| Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup, ITT estimand · 80 weeksRetatrutide 9 mg vs Placebo · ITT estimand | — not stated in the abstract | — not stated in the abstract | — not stated in the abstract | −9.6 events per hour | difference −24.7 | P < 0.001 |
| Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup, ITT estimand · 80 weeksRetatrutide 12 mg vs Placebo · ITT estimand | difference −22.5 | P < 0.001 |
— not stated in the abstract
- Co-primary: change in WOMAC pain score (1–10, higher worse), knee OA subgroup (n=574), hybrid estimand: values printed for the retatrutide groups in dose order 4 mg, 9 mg, 12 mg ("corresponding")
- Co-primary: change in WOMAC pain score, knee OA subgroup, ITT estimand: values printed for the retatrutide groups in dose order 4 mg, 9 mg, 12 mg ("corresponding")
- Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup (n=243), hybrid-treatment estimand: values printed for the retatrutide groups in dose order 4 mg, 9 mg, 12 mg ("corresponding")
- Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup (n=243), hybrid-treatment estimand: 12-mg value printed without a minus sign (31.7)
- Co-primary: change in apnea-hypopnea index (events per hour), obstructive sleep apnea subgroup, ITT estimand: values printed for the retatrutide groups in dose order 4 mg, 9 mg, 12 mg ("corresponding")
Original publication
Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. N Engl J Med. Published 29 September 2026. doi:10.
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