Empagliflozin does not rescue nor exacerbate doxorubicin-induced skeletal muscle wasting and metabolic dysfunction in male mice
Year: 2026
Type: article
Abstract: Doxorubicin (DOX) can induce skeletal muscle and white adipose tissue (WAT) wasting, contributing to treatment-related body mass loss, functional decline and compromised treatment efficacy. Impaired protein turnover and energy metabolism have been proposed as contributing mechanisms. Sodium–glucose cotransporter-2 inhibitors (SGLT2is) induce glucosuria and systemic metabolic adaptations that may improve skeletal muscle protein homeostasis and metabolic regulation. Concurrently, the glucosuria-induced caloric loss associated with SGLT2is may interfere with tissue wasting. This study investigated whether empagliflozin (EMPA) modifies DOX-induced tissue wasting in male mice. C57BL/6J mice ( n = 36) were randomized to control, EMPA, DOX, or DOX-EMPA groups. DOX (4 mg/kg/week, intraperitoneally) and EMPA (10 mg/kg/day, oral gavage) were administered for 6-weeks. Whole-body energy metabolism was assessed by indirect calorimetry, followed by tissue weight and molecular analyses in skeletal muscle and WAT. EMPA neither attenuated nor exacerbated DOX-induced body weight, skeletal muscle, or WAT loss. Despite effective glucosuria, EMPA did not increase non-fasted circulating β-hydroxybutyrate levels or meaningfully modify DOX-associated alterations in whole-body energy metabolism, tissue wasting, molecular markers of skeletal muscle protein turnover and metabolic regulation, or metabolic and stress-related gene expression in WAT. In conclusion, EMPA did not protect against DOX-induced tissue wasting and associated metabolic dysfunction, nor did it aggravate these effects.
Source: Scientific Reports
Institutions: University of Antwerp, KU Leuven, Antwerp University Hospital
Language: English
Subfield: Physiology (medical)
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
OpenAlex ID: W7223178943