Comparison of the urinary glucose excretion contributions ofSGLT2 and SGLT1: A quantitative systems pharmacologyanalysis in healthy individuals and patients with type2 diabetes treated with SGLT2 inhibitors

Tatiana Yakovleva et al.

Diabetes Obes Metab.2019;1–10

•A physiologically based model of renal glucose filtration, reabsorption and excretion via SGLT1/2 was developed based on published data on SGLT2 inhibitors pharmacokinetic and urinary glucose excretion (UGE) in healthy people and people with T2DM under the treatment​​​​​​​

•Quantitative drug-disease system modelling revealed mechanistic differences in renal glucose reabsorption and UGE between healthy people and those with T2DM, and clearly showed that SGLT2 inhibition significantly increased glucose available to SGLT1 downstream in the tubule.

•Higher renal glucose reabsorption in people with T2DM versus healthy people was associated with 54% and 28% greater transporter capacity for SGLT1 and SGLT2, respectively.

•Additionally, the analysis showed that UGE is highly dependent on mean plasma glucose and estimated glomerular filtration rate and that their consideration is critical for interpreting clinical UGE findings.

Please, see a more detailed presentation (Yakovleva slides.pdf) and a full text article (Diabetes Obes Metab (2019) 21, 2684-2693_Yakovleva.pdf)