Dronedarone hydrochloride reverses obesity-related metabolic syndrome while preserving skeletal muscle mass

Authors

Lei, J., Zhang, X., cao, x., zhu, z., ye, f., xu, z., su, w., zeng, x., xu, z., zhao, j., jiang, s., zhao, n., Liu, H., Lu, Y., Sun, C., Chai, J.

Abstract

Obesity-driven metabolic syndrome poses a critical global threat, yet standard therapies like GLP-1 receptor agonists trigger substantial lean mass wasting, with muscle loss accounting for up to 40% of reduced weight. Here we identify a non-canonical metabolic application for dronedarone hydrochloride, an anti-arrhythmic benzofuran derivative. In diet-induced and ob/ob obese mice, short-term dronedarone hydrochloride administration dose-dependently reduces food intake, clears visceral and subcutaneous adiposity, and reverses steatohepatitis. Head-to-head trials show that dronedarone hydrochloride achieves glycemic control and fat clearance non-inferior to semaglutide, tirzepatide, and empagliflozin, but uniquely and completely preserves skeletal muscle mass. Mechanistically, dronedarone hydrochloride operates independently of central hypothalamic appetite-regulating neuropeptides and the peripheral leptin pathway. By decoupling fat reduction from sarcopenia, our findings establish dronedarone hydrochloride as a muscle-sparing therapeutic candidate for metabolic syndrome.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 24 Jul 2026.

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