According to a research report, small nucleic acid drugs and GLP-1 based therapies demonstrate synergistic effects, with major weight loss companies already deploying small nucleic acid drug strategies. GLP-1 drugs control appetite, while small nucleic acids regulate metabolism, potentially forming a "golden combination" in the weight management field. In the future, GLP-1 receptor agonists may serve as the primary entry point for weight loss, with multinational corporations further developing small nucleic acid drugs to offer comprehensive weight management solutions. The primary small nucleic acid targets for weight loss are the INHBE target, the ARO-ALK7 target, and the muscle-targeting GeneD target. Chinese pharmaceutical companies are developing therapies for small nucleic acid weight loss indications at a pace nearly synchronized with overseas firms.
Arrowhead has reported promising preliminary weight loss efficacy for two small nucleic acid drugs. Arrowhead Pharmaceuticals announced positive initial efficacy data for its small nucleic acid drugs targeting INHBE and ALK7. ARO-INHBE demonstrated precise fat reduction, with an average fat reduction of 9.9% and a reduction in liver fat of up to 38.6%. ARO-INHBE also showed potential for increasing muscle mass, with a 3.6% increase in lean tissue observed in monotherapy. ARO-ALK7 showed a dose-dependent average reduction in ALK7 mRNA of up to 88%, confirming the TRiM platform's ability to suppress gene expression in fat cells. Following a single injection of ARO-ALK7, a rapid reduction in visceral fat mass of up to 14.1% was observed, based on data adjusted against a placebo control.
Wave Life Sciences' INHBE-targeting small nucleic acid drug WVE-007 also shows favorable weight loss results. Wave Life Sciences released Phase I small-sample data on December 8, 2025, for WVE-007. Targeting liver INHBE, a single 240mg dose administered three months prior resulted in a 9.4% reduction in visceral fat, a 4.5% reduction in total body fat, and a concurrent 3.2% increase in lean body mass.
Small nucleic acid drugs and GLP-1 therapies exhibit synergistic effects, prompting major weight loss players to invest in small nucleic acid drug development. GLP-1 agents control food intake, while small nucleic acids modulate metabolism, positioning them as a potential "golden pair" for weight management. Used following GLP-1 therapy, they could help maintain weight loss and prevent rebound. In November 2025, Eli Lilly collaborated with Shengjin Biotech in a $1.2 billion deal, utilizing a twice-yearly LEAD platform to co-develop RNAi candidates for metabolic diseases. In September 2024, Eli Lilly invested $1 billion in HAYA's lncRNA platform to develop drugs for obesity and related metabolic disorders. On August 28, 2025, Novo Nordisk entered a $550 million collaboration with Replicate Bioscience to develop novel therapies for obesity, type 2 diabetes, and other cardiometabolic diseases.
The report suggests that GLP-1 receptor agonists may become the primary gateway in the weight loss sector, with multinational corporations subsequently integrating small nucleic acid drugs to deliver end-to-end weight reduction programs. Furthermore, the validated efficacy of small nucleic acids for weight loss provides an opportunity for multinational corporations that missed the initial GLP-1 wave to re-enter the weight management market.
Chinese pharmaceutical companies are advancing small nucleic acid therapies for weight loss at a pace nearly keeping up with international peers. The main small nucleic acid targets for weight loss are the INHBE target, the ARO-ALK7 target, and the muscle-targeting GeneD target. The development speed in China is almost on par with the international pace. Hengrui Pharmaceuticals' INHBE-targeting HRS-5817 is in Phase I clinical trials. Innovative drug developers with major GLP-1 products, such as Innovent Biologics, have filed patents for INHBE-targeting small nucleic acid drugs, potentially future candidates for combination or sequential therapy with Mazdutide to leverage product synergy. Sino Biopharm, through its acquisition of Hejiya, holds the long-acting small nucleic acid drug HJY-10 targeting INHBE, administered once every six months or annually, which is expected to enter clinical stages in 2026.
Investment recommendations suggest focusing on small nucleic acid companies developing weight loss targets. Recommended companies include Hengrui Pharma (01276), HitGen (688222.SH), Sino Biopharm (01177), Huadong Medicine (000963.SZ), Salubris (002294.SZ), CMS (00867), Innovent Biologics (01801), and HEC Pharm (06887).
Risk factors include potential lower-than-expected pricing due to healthcare insurance and centralized procurement policies, clinical trial or approval timelines falling short of expectations, and uncertainties in the competitive landscape.