Comparative ADMET Profiling and Pharmacokinetic Assessment of Metformin and Empagliflozin for Drug Repurposing Potential in CKD

By Shroff Rishabh Ajay, Sanjana Bhatu Vasaikar, Nikhil Anil Shinde, Govind Dilip Pawar*, Vaishali Dadaji Shewale

NTVS Institute of Pharmacy, Nandurbar (MS), India

Published: April 2026 | DOI: 10.5281/zenodo.19848417 | Download PDF

Abstract

Chronic kidney disease (CKD) is a progressive disorder requiring improved therapeutic strategies. This study performed a comparative in silico ADMET and pharmacokinetic analysis of Metformin and Empagliflozin to evaluate their repurposing potential in CKD. The results showed that Empagliflozin exhibited a more balanced pharmacokinetic profile with better absorption, distribution, and clearance, while Metformin showed limitations due to renal accumulation risk. The findings support SGLT2 inhibitors as promising candidates for CKD management.

Keywords:

Chronic Kidney Disease, Metformin, Empagliflozin, ADMET Analysis, Pharmacokinetics, Drug Repurposing

Introduction

Chronic Kidney Disease (CKD) is a progressive condition characterized by declining renal function and increased cardiovascular risk. Current therapies focus on slowing disease progression, highlighting the need for novel approaches such as drug repurposing. Metformin and Empagliflozin are widely used antidiabetic drugs with potential renoprotective effects.

Materials and Methods

An in silico comparative study was conducted using DeepPK, a deep learning-based platform for ADMET prediction. Chemical structures were retrieved from PubChem and analyzed for absorption, distribution, metabolism, excretion, and toxicity parameters. Comparative evaluation was performed to determine suitability for CKD.

Results and Discussion

Both drugs demonstrated good intestinal absorption. Empagliflozin showed better pharmacokinetic stability with reduced transporter dependency and higher free drug availability. According to the comparative tables on page 5–6, it also exhibited higher clearance, reducing accumulation risk in CKD patients.

Metabolic analysis showed minimal drug interaction risk for both drugs, while excretion patterns highlighted the renal dependency of Metformin, increasing risk in advanced CKD. Toxicity predictions indicated relatively safer profiles for SGLT2 inhibitors overall.

Conclusion

Empagliflozin demonstrates superior pharmacokinetic characteristics and reduced renal dependency compared to Metformin, making it a more suitable candidate for CKD drug repurposing. However, further experimental and clinical validation is required.

References

  1. Levin A. Global kidney health.
  2. Pushpakom S. Drug repurposing.
  3. Zinman B. Empagliflozin outcomes.
  4. Additional references as per original article.