An Arrowhead RNA drug roughly doubles tirzepatide's weight loss in an early trial

Arrowhead Pharmaceuticals said an experimental RNA interference drug, when combined with Eli Lilly's tirzepatide, produced roughly double the weight loss seen with tirzepatide alone in an early-stage trial. The company's stock jumped 17% to $75.20 a share on the news.^[2]

The interim results come from small groups of patients in two ongoing Phase I/IIa trials testing Arrowhead's RNAi candidates ARO-INHBE and ARO-ALK7. In one comparison, four patients with type 2 diabetes who took ARO-INHBE alongside tirzepatide lost 9.4% of their body weight at 16 weeks. Five patients who took tirzepatide by itself lost 4.8% over the same period. Arrowhead described this as a doubling of tirzepatide's effect.^[2]

Beyond weight on the scale, the combination also appeared to affect body composition. In just three patients, ARO-INHBE tripled the reduction in visceral fat, total fat and liver fat compared with tirzepatide alone. When tested without tirzepatide, ARO-INHBE reduced visceral fat by 9.9%, cut liver fat by 38%, and increased total lean tissue by 3.6%, with a placebo-adjusted visceral fat reduction of 15.6% at 24 weeks.^[2]

A second Arrowhead drug, ARO-ALK7, produced the first documented case of gene target silencing by this type of drug, according to the company, reducing a fat-tissue gene called ALK7 by 88% at eight weeks and cutting visceral fat by 14.1% compared with placebo. Arrowhead said the drug was well tolerated.^[2] Safety findings across both trials were reported as mild, with no discontinuations due to side effects, one unrelated limb abscess, similar gastrointestinal side effects between the combination and tirzepatide-alone groups, and no meaningful changes in liver enzymes, blood sugar markers or cholesterol on lab tests.^[2]

Analysts at Truist Securities called the weight loss numbers "substantial" and "meaningful," and said the data could revive investor and physician interest in weight loss quality — meaning how much of the weight lost is fat versus muscle — at a time when attention had shifted toward new pill options from Lilly and Novo Nordisk. Truist noted that specialists in metabolic disease remain concerned about the long-term effects of weight loss that isn't paired with more targeted therapies. Other companies working on similar body-composition drugs include Scholar Rock, Lilly itself with a drug called bimagrumab, and Wave Life Sciences.^[2]

Why it matters for patients

These results are early and small — four patients in the key combination group, five in the comparison group, and as few as three patients for some fat measurements. That is far too few people to know how the drugs would perform in a larger, more diverse population, or over a longer period of time. Still, the direction of the data suggests that RNA-based drugs might one day be added to tirzepatide (sold as Mounjaro and Zepbound) rather than compete with it, similar to how other add-on therapies are being explored. Arrowhead's drug is injectable, so it would not directly compete with Lilly's oral orforglipron (Foundayo), which analysts said could reach the market as early as March if the FDA approves it.^[2] For patients currently on tirzepatide, none of this changes what's available today. Any combination therapy would need much larger studies, FDA review, and eventually a price and insurance decision before it could reach patients.

What happens next

Arrowhead said both Phase I/IIa trials are continuing, with more data expected later in 2026.^[2] The company's first FDA approval, for an unrelated drug called plozasiran (brand name Redemplo) treating a rare fat-metabolism disorder, came in November 2025, giving Arrowhead a track record with regulators.^[2] Whether ARO-INHBE or ARO-ALK7 advance to larger trials, and how they might be priced or combined with tirzepatide commercially, is not yet known.