The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes
Open accessAbstract
OBJECTIVE: To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on the major components of renal glucose reabsorption (decreased maximum renal glucose reabsorptive capacity [TmG], increased splay, and reduced threshold), using the pancreatic/stepped hyperglycemic clamp (SHC) technique. RESEARCH DESIGN AND METHODS: Subjects with type 2 diabetes (n = 12) and matched healthy subjects (n = 12) underwent pancreatic/SHC (plasma glucose range 5.5–30.5 mmol/L) at baseline and after 7 days of dapagliflozin treatment. A pharmacodynamic model was developed to describe the major components of renal glucose reabsorption for both groups and then used to estimate these parameters from individual glucose titration curves. RESULTS: At baseline, type 2 diabetic subjects had elevated TmG, splay, and threshold compared with controls. Dapagliflozin treatment reduced the TmG and splay in both groups. However, the most significant effect of dapagliflozin was a reduction of the renal threshold for glucose excretion in type 2 diabetic and control subjects. CONCLUSIONS: The SGLT2 inhibitor dapagliflozin improves glycemic control in diabetic patients by reducing the TmG and threshold at which glucose is excreted in the urine.
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“Studies with inhibitors of the SGLT2 transporter indeed showed that these drugs decrease the glucose reabsorption capacity of the proximal tubule, thereby acutely increasing glycosuria and improving glycemic control over time (DeFronzo et al., 2013).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as DeFronzo et al., 2013
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Glucose clamp technique: a method for quantifying insulin secretion and resistance.
DeFronzo, R. A., Tobin, J. D., & Andres, R. (1979) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1979.237.3.e214 · Cited by 7,425
Self-citationDeFronzo, R. A. (2009) · Diabetes · doi:10.2337/db09-9028 · Cited by 3,016
Self-citationAssessing Kidney Function — Measured and Estimated Glomerular Filtration Rate
Stevens, L. A., Coresh, J., Greene, T., & Levey, A. S. (2006) · New England Journal of Medicine · doi:10.1056/nejmra054415 · Cited by 2,952
Biology of Human Sodium Glucose Transporters
Wright, E. M., Loo, D. D. F., & Hirayama, B. A. (2011) · Physiological Reviews · doi:10.1152/physrev.00055.2009 · Cited by 1,430
Bailey, C. J., Gross, J. L., Pieters, A., Bastien, A., & List, J. F. (2010) · The Lancet · doi:10.1016/s0140-6736(10)60407-2 · Cited by 873
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Ferrannini, E., Ramos, S. J., Salsali, A., Tang, W., & List, J. F. (2010) · Diabetes Care · doi:10.2337/dc10-0612 · Cited by 725
Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes
List, J. F., Woo, V., Morales, E., Tang, W., & Fiedorek, F. T. (2009) · Diabetes Care · doi:10.2337/dc08-1863 · Cited by 698
SGLT2 Mediates Glucose Reabsorption in the Early Proximal Tubule
Vallon, V., Platt, K. A., Cunard, R. A., Schroth, J., Whaley, J. M., Thomson, S. C., Koepsell, H., & Rieg, T. (2010) · Journal of the American Society of Nephrology · doi:10.1681/asn.2010030246 · Cited by 565
Role of Sodium-Glucose Cotransporter 2 (SGLT 2) Inhibitors in the Treatment of Type 2 Diabetes
Abdul‐Ghani, M. A., Norton, L., & DeFronzo, R. A. (2011) · Endocrine Reviews · doi:10.1210/er.2010-0029 · Cited by 454
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DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Self-citationInflammation and atherosclerosis: signaling pathways and therapeutic intervention
Kong, P., Cui, Z.-Y., Huang, X.-F., Zhang, D.-D., Guo, R.-J., & Han, M. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00955-7 · Cited by 1,183
Pathophysiology of diabetic kidney disease: impact of SGLT2 inhibitors
DeFronzo, R. A., Reeves, W. B., & Awad, A. S. (2021) · Nature Reviews Nephrology · doi:10.1038/s41581-021-00393-8 · Cited by 627
Self-citationRenal, metabolic and cardiovascular considerations of SGLT2 inhibition
DeFronzo, R. A., Norton, L., & Abdul‐Ghani, M. A. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.170 · Cited by 588
Self-citationThe tubular hypothesis of nephron filtration and diabetic kidney disease
Vallon, V., & Thomson, S. C. (2020) · Nature Reviews Nephrology · doi:10.1038/s41581-020-0256-y · Cited by 465
Metadata
- Authors
- DeFronzo, R. A., Hompesch, M., Kasichayanula, S., Liu, X., Hong, Y., Pfister, M., Morrow, L. A., Leslie, B. R., Boulton, D. W., Ching, A., LaCreta, F. P., & Griffen, S. C.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Profil Institute for Clinical Research (US)
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- DeFronzo, Ralph A.
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2013-09-14
- Volume
- 36
- Issue
- 10
- Pages
- 3169-3176
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- PMC
- PMC3781504
- OpenAlex
- W2120922908
- Cited by
- 293
- References
- 26
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 22 · 2023: 27 · 2022: 17 · 2021: 22 · 2020: 22 · 2019: 23 · 2018: 30 · 2017: 24 · 2016: 30 · 2015: 24 · 2014: 22 · 2013: 1
- FWCI
- 20.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Care (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R56DK024092)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- dapagliflozin, SGLT2 inhibitors, renal glucose reabsorption, type 2 diabetes, renal glucose threshold, pharmacodynamic modeling, glycemic control
- MeSH terms
- Adult, Benzhydryl Compounds, Diabetes Mellitus, Type 2, Female, Glucose, Glucosides, Humans, Hypoglycemic Agents, Kidney, Male, Middle Aged, Sodium-Glucose Transport Proteins
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