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Characterization of Renal Glucose Reabsorption in Response to Dapagliflozin in Healthy Subjects and Subjects With Type 2 Diabetes
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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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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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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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