Pharmacokinetic Landscape and Interaction Potential of SGLT2 Inhibitors: Bridging In Vitro Findings and Clinical Implications
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes and cardiometabolic diseases, and their pharmacokinetic characteristics generally confer a low risk of clinically relevant drug-drug interactions (DDIs). Most clinical studies demonstrate that these agents can be co-administered safely with commonly prescribed medications without dose adjustment, although strong enzyme inducers such as rifampin can reduce systemic exposure, and pharmacodynamic interactions may still arise. However, existing evidence is largely derived from short-term studies in healthy volunteers, with limited data in special populations and minimal evaluation of metabolite- or transporter-mediated interactions. This review summarizes the available in vitro and in vivo pharmacokinetic and DDI data for SGLT2 inhibitors, identifies key knowledge gaps related to polypharmacy, metabolite effects, and vulnerable patient groups, and outlines future research priorities to ensure their safe and effective use in real-world clinical practice.
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