DOI: https://doi.org/10.14710/dmj.v15i4.53412

COMPARATIVE DOCKING ANALYSIS REVEALS DIVERGENT SGLT2 SELECTIVITY, FAVORING DAPAGLIFLOZIN

*I Dewa Agung Panji Dwipayana orcid  -  Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Udayana, Indonesia
Ni Luh Putu Kayika Febryanti  -  Department of Marine Sciences, Faculty of Marine Science and Fisheries, Universitas Udayana, Indonesia
Made Pharmawati  -  Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Udayana, Indonesia
Open Access Copyright 2026 I Dewa Agung Panji Dwipayana, Ni Luh Putu Kayika Febryanti, Made Pharmawati
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

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Abstract

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are widely used in type 2 diabetes therapy, but selectivity over SGLT1 is critical to minimize gastrointestinal side effects. Objectives: To evaluate and compare the selectivity of SGLT inhibitors, especially Dapagliflozin and Empagliflozin, toward SGLT1 and SGLT2 through molecular docking to inform future inhibitor design. Methods: This study used molecular docking to compare the binding profiles of five SGLT inhibitors, Dapagliflozin, Empagliflozin, Canagliflozin, Sotagliflozin, and LX2761, against SGLT1 and SGLT2 transporters Results: Dapagliflozin was the only compound to show statistically significant selectivity for SGLT2 over SGLT1 (p = 0.036), while Empagliflozin and others lacked significant differences in isoform affinity. Although Empagliflozin exhibited slightly stronger nominal binding energy to SGLT2 than Dapagliflozin, ligand efficiency (LE) analysis indicated that this was primarily due to its larger molecular size, affirming Dapagliflozin’s more efficient binding. Interaction analysis further revealed that Dapagliflozin formed a clean, stabilizing pose within the SGLT2 pocket, free of repulsive interactions, unlike Empagliflozin, which displayed an unfavorable donor-donor contact in the same site. Conclusion: These findings support the structural basis for Dapagliflozin’s higher selectivity and reinforce its profile as a SGLT2-specific agent.

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Keywords: dapagliflozin, empagliflozin, docking, ADME, Toxicity, SGLT1, SGLT2

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