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Triple Hormone Drug Cuts Body Weight 25% In 80-Week Obesity Trial

A phase 3 trial of a new weekly injection cut body weight by up to 25% over 80 weeks and eased knee pain and sleep apnea.

By Dr. Axe Editorial Team · October 6, 2026 · 1 source · Understand

Photo: Pexels

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.

17.6 to 25%weight loss

2,339adults

80weeks

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. The most common side effects were gastrointestinal.

Retatrutide activates three gut-hormone receptors at once: GIP, GLP-1 and glucagon. GLP-1 and GIP help signal fullness and regulate insulin, and glucagon acts on how the body uses stored energy. Current GLP-1 drugs act on one or two of these receptors. This trial compared retatrutide only with placebo, so it does not show how it stacks up against those drugs head to head.

Body weight change at 80 weeks: up to -25.0% vs -3.9% with placebo

New England Journal of Medicine, 2026, Jastreboff

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 on the top 12 mg dose is striking. Retatrutide isn't approved yet, so nothing changes today. These drugs 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 is real and under-discussed. Many people on approved GLP-1 medicines do well on a microdose, often 10 to 20% of the labeled dose, worked out with the prescribing doctor rather than adjusted on their own. Either way, build the muscle and metabolic foundation now so the weight does not return once the prescription ends.

— Dr. Axe

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Study summary

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
Date: Sep 29, 2026