Comparative ADMET Profiling and Pharmacokinetic Assessment of Selected Anti-Diabetic Drugs for Drug Repurposing Potential in Chronic Kidney Disease: A Study of Dapagliflozin and Sitagliptin

By Kalyani Deepak Padvi, Kalavati Rajya Valvi, Nitisha Bhausaheb Deore, Nilesh P. Salunkhe*, Vaishali D. Shewale

NTVS Institute of Pharmacy, Nandurbar (MS), India

Published: April 2026 | DOI: 10.5281/zenodo.19850441 | Download PDF

Abstract

Chronic kidney disease (CKD) is a progressive disorder requiring improved therapeutic strategies. This study performs a comparative in silico ADMET evaluation of Dapagliflozin and Sitagliptin to assess their suitability for drug repurposing. Both drugs showed good absorption and bioavailability. Dapagliflozin demonstrated superior distribution and tissue penetration, whereas Sitagliptin showed better metabolic stability and longer half-life. Toxicity analysis revealed higher risks for Dapagliflozin, while Sitagliptin exhibited a safer profile. The study suggests Sitagliptin as a more suitable candidate for CKD drug repurposing.

Keywords:

Dapagliflozin, Sitagliptin, Chronic Kidney Disease, ADMET Profiling, Pharmacokinetics, Drug Repurposing

Introduction

Chronic kidney disease (CKD) is a progressive condition associated with declining renal function and increased morbidity. Diabetes mellitus is a leading cause of CKD. Drug repurposing provides a cost-effective strategy to identify new therapeutic uses for existing drugs. Antidiabetic drugs such as Dapagliflozin (SGLT2 inhibitor) and Sitagliptin (DPP-4 inhibitor) have shown potential renoprotective effects beyond glycemic control.

Materials and Methods

An in silico comparative study was conducted using the DeepPK platform. Chemical structures were retrieved from PubChem in SMILES format and analyzed for absorption, distribution, metabolism, excretion, toxicity, and physicochemical properties. Comparative evaluation focused on parameters relevant to CKD such as clearance, half-life, and toxicity endpoints.

Results and Discussion

According to the absorption table on page 5, both drugs showed high intestinal absorption and oral bioavailability. Dapagliflozin exhibited slightly better permeability and acted as a P-glycoprotein inhibitor, whereas Sitagliptin was identified as a substrate.

Distribution analysis (page 6) indicated that Dapagliflozin had higher volume of distribution and fraction unbound, suggesting better tissue penetration. Both drugs were predicted to cross the blood–brain barrier.

Metabolic evaluation showed minimal CYP interactions for both drugs, although Dapagliflozin is a CYP3A4 substrate, while Sitagliptin demonstrated greater metabolic stability.

Excretion analysis revealed higher clearance and shorter half-life for Dapagliflozin, while Sitagliptin showed longer systemic persistence. Toxicity data (page 7) indicated mutagenicity and cardiotoxicity risks for Dapagliflozin, whereas Sitagliptin exhibited a comparatively safer toxicity profile.

Conclusion

Both drugs demonstrate favorable pharmacokinetic properties; however, Sitagliptin provides a more balanced profile with improved safety and metabolic stability. Therefore, Sitagliptin is a more promising candidate for drug repurposing in chronic kidney disease, although further experimental validation is required.

References

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  3. Heerspink HJL. Dapagliflozin CKD outcomes.
  4. Additional references as per original article.