Empagliflozin, a novel selective sodium glucose cotransporter‐2 (SGLT‐2) inhibitor: characterisation and comparison with other SGLT‐2 inhibitors
Abstract
Aims Empagliflozin is a selective sodium glucose cotransporter-2 (SGLT-2) inhibitor in clinical development for the treatment of type 2 diabetes mellitus. This study assessed pharmacological properties of empagliflozin in vitro and pharmacokinetic properties in vivo and compared its potency and selectivity with other SGLT-2 inhibitors. Methods [(14)C]-alpha-methyl glucopyranoside (AMG) uptake experiments were performed with stable cell lines over-expressing human (h) SGLT-1, 2 and 4. Two new cell lines over-expressing hSGLT-5 and hSGLT-6 were established and [(14)C]-mannose and [(14)C]-myo-inositol uptake assays developed. Binding kinetics were analysed using a radioligand binding assay with [(3)H]-labelled empagliflozin and HEK293-hSGLT-2 cell membranes. Acute in vivo assessment of pharmacokinetics was performed with normoglycaemic beagle dogs and Zucker diabetic fatty (ZDF) rats. Results Empagliflozin has an IC(50) of 3.1 nM for hSGLT-2. Its binding to SGLT-2 is competitive with glucose (half-life approximately 1 h). Compared with other SGLT-2 inhibitors, empagliflozin has a high degree of selectivity over SGLT-1, 4, 5 and 6. Species differences in SGLT-1 selectivity were identified. Empagliflozin pharmacokinetics in ZDF rats were characterised by moderate total plasma clearance (CL) and bioavailability (BA), while in beagle dogs CL was low and BA was high. Conclusions Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the h…
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Empagliflozin is a selective inhibitor of sodium glucose cotransporter 2.
“Empagliflozin is a selective inhibitor of sodium glucose cotransporter 2 11”
From Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (2015) · cites this paper as [11]
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Inzucchi, S. E., Zinman, B., Fitchett, D., Wanner, C., Ferrannini, E., Schumacher, M., Schmoor, C., Ohneberg, K., Johansen, O. E., George, J. T., et al. (2018) · Diabetes Care · doi:10.2337/dc17-1096 · Cited by 740 · see citing works
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McMurray, J. J. V., DeMets, D. L., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Langkilde, A. M., Martinez, F. A., Bengtsson, O., Ponikowski, P., Sabatine, M. S., et al. (2019) · European Journal of Heart Failure · doi:10.1002/ejhf.1432 · Cited by 433 · see citing works
Lin, B., Koibuchi, N., Hasegawa, Y., Sueta, D., Toyama, K., Uekawa, K., Ma, M., Nakagawa, T., Kusaka, H., & Kim-Mitsuyama, S. (2014) · Cardiovascular Diabetology · doi:10.1186/s12933-014-0148-1 · Cited by 423 · see citing works
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Liu, Z., Ma, X., Ilyas, I., Zheng, X., Luo, S., Little, P. J., Kamato, D., Sahebkar, A., Wu, W., Weng, J., et al. (2021) · Theranostics · doi:10.7150/thno.54498 · Cited by 155 · see citing works
Tahara, A., Takasu, T., Yokono, M., Imamura, M., & Kurosaki, E. (2016) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2016.02.003 · Cited by 148 · see citing works
Tanaka, H., Takano, K., Iijima, H., Kubo, H., Maruyama, N., Hashimoto, T., Arakawa, K., Togo, M., Inagaki, N., & Kaku, K. (2017) · Advances in Therapy · doi:10.1007/s12325-016-0457-8 · Cited by 140 · see citing works
Wu, C.-Y., Iskander, C., Wang, C., Xiong, L. Y., Shah, B. R., Edwards, J. D., Kapral, M. K., Herrmann, N., Lanctôt, K. L., Masellis, M., et al. (2023) · Diabetes Care · doi:10.2337/dc22-1705 · Cited by 139 · see citing works
Lee, N., Heo, Y. J., Choi, S.-E., Jeon, J. Y., Han, S. J., Kim, D. J., Kang, Y., Lee, K. W., & Kim, H. J. (2021) · Journal of Immunology Research · doi:10.1155/2021/9944880 · Cited by 139 · see citing works
Xu, L., & Ota, T. (2017) · Adipocyte · doi:10.1080/21623945.2017.1413516 · Cited by 134 · see citing works
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Jordan, J., Tank, J., Heusser, K., Heise, T., Wanner, C., Heer, M., Macha, S., Mattheus, M., Lund, S. S., Woerle, H. J., et al. (2017) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2017.07.005 · Cited by 102 · see citing works
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Trujillo, J. M., & Nuffer, W. A. (2017) · Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy · doi:10.1002/phar.1903 · Cited by 42 · see citing works
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- Authors
- Grempler, R., Thomas, L., Eckhardt, M., Himmelsbach, F., Sauer, A., Sharp, D. E., Bakker, R. A., Mark, M., Klein, T., & Eickelmann, P.
- Affiliations
- Boehringer Ingelheim (Germany) (DE)
- Boehringer Ingelheim (United States) (US)
- Corresponding author
- Grempler, R.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2011-11-13
- Volume
- 14
- Issue
- 1
- Pages
- 83-90
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W2134855422
- Cited by
- 608
- References
- 0
- Citations by year
- 2026: 31 · 2025: 35 · 2024: 34 · 2023: 38 · 2022: 50 · 2021: 46 · 2020: 51 · 2019: 46 · 2018: 35 · 2017: 44 · 2016: 45 · 2015: 48 · 2014: 50 · 2013: 39 · 2012: 12
- FWCI
- 27.51
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Boehringer Ingelheim
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Natural Antidiabetic Agents Studies
- Keywords
- empagliflozin, SGLT2 inhibitors, SGLT2, type 2 diabetes, binding kinetics, competitive inhibition, pharmacokinetics, bioavailability, plasma clearance, species differences, Zucker diabetic fatty rats, beagle dogs, myo-inositol uptake
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Benzhydryl Compounds, Blood Glucose, Diabetes Mellitus, Type 2, Dogs, Glucosides, Hypoglycemic Agents, Monosaccharide Transport Proteins, Rats, Zucker, Rats
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