Pharmacokinetic and pharmacodynamic interaction of DWP16001, a sodium-glucose cotransporter-2 inhibitor, with phentermine in healthy subjects

ABSTRACT

Background

DWP16001, a sodium-glucose cotransporter-2 inhibitor, has shown promise for improving blood glucose control and facilitating weight loss. Co-administration with phentermine could enhance these effects. So, we aimed to evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) interactions of DWP16001 and phentermine.

Methods

We conducted a randomized, open-label, 3-treatment, 6-sequence, 3-period crossover study involving 24 healthy adults. Participants received either DWP16001 (2 mg), phentermine (37.5 mg), or a combination of both once daily for 7 days. Blood samples, urine samples, and body weights were collected to evaluate the PK and PD.

Results

The PK of the combination was found to be similar to that of the monotherapy. The geometric mean ratio (GMR) of C_max,ss, and AUC_tau,ss were 0.98 and 1.00, respectively, for DWP16001, and 1.01 and 0.94, respectively, for phentermine. Co-administration did not significantly affect the 24-hour urinary glucose excretion compared to DWP16001 monotherapy, and the GMR was 0.90. Participants tended to experience greater weight loss in the combination therapy group, and all demonstrated good tolerance.

Conclusions

Our findings indicate that there were no significant interactions during co-administration. These results suggest that the combination of DWP16001 and phentermine may be safe and effective for the treatment of obesity and diabetes.

Clinical trial registration

NCT05321732

KEYWORDS:

• Drug interaction
• DWP16001
• pharmacodynamics
• pharmacokinetics
• phentermine

Declaration of interest

H Shin, J Na and W Huh are employees of Daewoong Pharmaceutical Co., Ltd., Korea. The other authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors substantially contributed to the conception and design of the study, reviewed and agreed on all versions of the article, and agreed to be accountable for the contents of the article. Conception and design: S Yoon, MS Park, BH Jin, H Shin, J Na, W Huh and CO Kim. Analysis and interpretation of the data: S Yoon, MS Park, BH Jin, CO Kim. Drafting of the manuscript: S Yoon, CO Kim. All authors approved the final version of the article.

Acknowledgments

We would like to thank the staff at the Severance Hospital Clinical Trials Center for their cooperation. Clinical trial registration: NCT05321732

Data availability statement

The data supporting the findings of this study are not available because of confidentiality.

SUPPLEMENTARY MATERIAL

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17425255.2023.2249397

Additional information

Funding

This manuscript was funded by Daewoong Pharmaceutical Co., Ltd., Korea.