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Study decoded · health · hormones · Confirmed
Triple Hormone Drug Cuts Body Weight 25% In 80-Week Obesity Trial
25% weight loss2,339 adults80 weeksKnee pain easedSleep apnea improved
A new triple-hormone-receptor drug called retatrutide produced up to 25% body weight loss over 80 weeks, according to a phase 3 trial published in the New England Journal of Medicine.
In this placebo-controlled trial, researchers randomly assigned 2,339 adults with obesity but no diabetes to a once-weekly injection of retatrutide at 4 mg, 9 mg or 12 mg, or to a placebo shot, for 80 weeks. Average body weight dropped 17.6% in the 4-mg group, 23.7% in the 9-mg group and 25.0% in the 12-mg group, compared with 3.9% in the placebo group. Compared with placebo, the two higher doses cut weight by a further 19.8 and 21.0 percentage points. Among 574 participants who also had knee osteoarthritis, those on the drug reported less pain on a standard 1-to-10 pain scale. Among 243 participants with obstructive sleep apnea, the number of breathing interruptions during sleep, measured by the apnea-hypopnea index, went down.
Retatrutide works by activating three separate gut-hormone receptors at once: GIP, GLP-1 and glucagon. GLP-1 and GIP are hormones that signal fullness to the brain and help regulate insulin; glucagon receptor activity adds an effect on energy burning. The authors say combining all three produces a stronger effect on appetite and metabolism than drugs that hit only one or two of these targets, which may explain why the weight loss numbers here run higher than typical results from single-hormone or dual-hormone drugs.
Body weight change at 80 weeks: up to -25.0% vs -3.9% with placebo
Data Panel
- Who
- 2,339 adults with obesity, without diabetes; subgroups of 574 with knee osteoarthritis and 243 with obstructive sleep apnea
- Design
- Phase 3 randomized, placebo-controlled trial, 80 weeks
- Dose
- Once-weekly subcutaneous injection of retatrutide at 4 mg, 9 mg or 12 mg, versus placebo
- Primary result
- Body weight change: -17.6% (4 mg), -23.7% (9 mg), -25.0% (12 mg) versus -3.9% with placebo; differences of 19.8 and 21.0 percentage points for the 9-mg and 12-mg doses versus placebo
- Secondary
- Reduced knee pain on the WOMAC pain scale (1-10) in participants with knee osteoarthritis; reduced apnea-hypopnea index (breathing interruptions during sleep) in participants with obstructive sleep apnea; exact point changes not reported in abstract
- Funding / conflicts
- Funded by Eli Lilly; registered as TRIUMPH-1, NCT05929066
The trial was funded by Eli Lilly, the drug's manufacturer, and the authors include employees of the company. The abstract does not report what happens to weight, joint pain or sleep apnea scores after people stop taking the drug, a known issue with this drug class.
Dr. Axe's Take
A 25% body weight loss at 80 weeks is the strongest number I have seen from a drug in this category, and it deserves to be taken seriously. My view on these drugs has not changed: they work best paired with a high-protein, whole-food diet, fiber from vegetables and resistance training at least three days a week, because the muscle loss that comes with rapid weight loss on these drugs is real and under-discussed. I also favor a microdose, often 10 to 20% of the labeled dose, rather than chasing the biggest number; work that out with the prescribing doctor instead of adjusting on your own. Either way, build the muscle and metabolic foundation now so the weight does not return once the prescription ends.
— Dr. Axe