Research
Hormonal
SGLT2 inhibition (canagliflozin) reduces adiposity and activates lipolysis exclusively through FGF21-dependent mechanisms, while its effects on lipid oxidation, ketogenesis, and hepatic steatosis reduction are FGF21-independent.
SGLT2 inhibitors reduce body fat by triggering a hormonal signal (FGF21) that activates fat burning (lipolysis). This process is distinct from simple calorie restriction and requires the presence of FGF21 to effectively reduce fat mass.
GoodQualifiesHIGH confidence
Using FGF21-null mice, we demonstrate that FGF21 is not required for SGLT2i-mediated induction of lipid oxidation and ketogenesis but is required for reduction in fat mass and activation of lipolysis.
Why this rating
Strong evidence using FGF21-knockout mice demonstrating causal necessity for specific phenotypes.
Source
SGLT2 inhibition reprograms systemic metabolism via FGF21-dependent and -independent mechanisms
Soravis Osataphan et al. · JCI Insight · 2019
DOI 10.1172/jci.insight.123130
mechanism_onlyCited 228×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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