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Pharmacogenetics of sodium‐glucose co‐transporter‐2 inhibitors: Validation of a sex‐agnostic pharmacodynamic biomarker by Simeon I. Taylor; Hua‐Ren Cherng; Zhinous Shahidzadeh Yazdi; May E. Montasser; Hilary B. Whitlatch; Braxton D. Mitchell; Alan R. Shuldiner; Elizabeth A. Streeten; Amber L. Beitelshees is a Medicine article available to read on EtoBox.
What is Pharmacogenetics of sodium‐glucose co‐transporter‐2 inhibitors: Validation of a sex‐agnostic pharmacodynamic biomarker about?
## Abstract ## Aim To validate pharmacodynamic responses to sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9. ## Methods Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug‐induced increases in urinary excretion of glucose, sodium and uric acid. ## Results This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (−4.1 mg/dL; P = 6 × 10^−5^), serum creatinine (+0.05 mg/dL; P = 8 × 10^−4^) and serum uric acid (−0.90 mg/dL; P = 5 × 10^−10^). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram‐creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with
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- Author
- Simeon I. Taylor; Hua‐Ren Cherng; Zhinous Shahidzadeh Yazdi; May E. Montasser; Hilary B. Whitlatch; Braxton D. Mitchell; Alan R. Shuldiner; Elizabeth A. Streeten; Amber L. Beitelshees
- Publisher
- Wiley
- Published
- 2023
- Language
- EN
- Field
- Medicine (Health Sciences)