Pharmacokinetic and pharmacodynamic interaction between DWP16001, an sodium–glucose cotransporter 2 inhibitor and metformin in healthy subjects

• Published in: British journal of clinical pharmacology Vol. 89; no. 4; pp. 1462 - 1470
• Main Authors: Kim, Byungwook, Huh, Ki Young, Hwang, Jun Gi, Nah, JaeJin, Huh, Wan, Cho, Jae Min, Jang, In‐Jin, Yu, Kyung‐Sang, Kim, Yun, Lee, SeungHwan
• Format: Journal Article
• Language: English
• Published: England 01-04-2023
• Subjects: Area Under Curve; Cross-Over Studies; diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; drug interaction; Glucose; Healthy Volunteers; Humans; Hypoglycemic Agents - adverse effects; Male; Metformin; pharmacodynamics; pharmacokinetics; SGLT2 inhibitor; Sodium; pharmacokinetics; diabetes mellitus; SGLT2 inhibitor; drug interaction; pharmacodynamics
• ISSN: 0306-5251; 1365-2125
• DOI: 10.1111/bcp.15613

Aims
DWP16001 is a novel sodium–glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes with selective and sustained sodium–glucose cotransporter 2 inhibition. We aimed to evaluate whether the coadministration of DWP16001 and metformin causes any changes in pharmacokinetics (PK) or pharmacodynamics (PD).
Methods
A randomized, open‐label, single‐ and multiple‐dose, 2‐sequence, crossover study was conducted in healthy male subjects. Subjects received the following treatments: a single oral dose of DWP16001 (DWP) 2 mg, metformin immediate release 1000 mg (MET) twice daily for 7 days and a single oral dose of DWP and MET at steady‐state for metformin (DWP+MET). Serial blood and interval urine were collected for PK and PD analyses. Safety and tolerability profiles were assessed throughout the study.
Results
DWP+MET displayed increased peak concentration and area under the concentration–time curve from time 0 to time of the last quantifiable concentration compared with DWP (per standard bioequivalence boundaries, 0.8–1.25); the geometric mean ratios (GMRs) and their 90% confidence intervals (CIs) were 1.22 (1.13–1.31) and 1.09 (1.05–1.14), respectively. DWP+MET and MET showed similar peak concentration and area under the concentration–time curve within a dosing interval at steady state for metformin; the GMRs and 90% CIs were 0.98 (0.90–1.06) and 1.05 (0.98–1.13), respectively. The amount of urinary glucose excretion from time 0 to 144 h was also comparable between DWP+MET and DWP (GMR and 90% CI; 0.99, 0.94–1.05).
Conclusion
The results suggest that DWP16001 and metformin could be coadministered without clinically relevant PK and PD interactions.