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Cited by 293Diabetes Treatment and ManagementDiabetes Management and ResearchChronic Kidney Disease and Diabetes

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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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DeFronzo, Ralph A., Hompesch, Marcus, Kasichayanula, Sreeneeranj, Liu, Xiaoni, Hong, Ying, Pfister, Marc, Morrow, Linda A., Leslie, Bruce R., Boulton, David W., Ching, Agatha, LaCreta, Frank P., Griffen, Steven C.·2013·Diabetes Care
DOI 10.2337/dc13-0387PMC PMC3781504
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Abstract

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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Figure 1 Relationship between the rate of urinary glucose reabsorption/renal glucose filtration and the plasma glucose concentration during SHC in type 2 diabetic and healthy subjects at baseline and after 7 days of dapagliflozin treatment. Thin line, rate of glucose filtration; ○, observed rate of reabsorption; thick line, predicted rate of reabsorption; dashed line, geometric mean of TmG.
Figure 1 Relationship between the rate of urinary glucose reabsorption/renal glucose filtration and the plasma glucose concentration during SHC in type 2 diabetic and healthy subjects at baseline and after 7 days of dapagliflozin treatment. Thin line, rate of glucose filtration; ○, observed rate of reabsorption; thick line, predicted rate of reabsorption; dashed line, geometric mean of TmG.CC BY-NC-ND · PubMed Central
Figure 2 TmG in type 2 diabetic and healthy subjects at baseline and after 7 days of dapagliflozin treatment. A: TmG for all subjects. B: TmG for all 12 subjects with type 2 diabetes and 11 healthy subjects minus 1 outlier, which is shown separately.
Figure 2 TmG in type 2 diabetic and healthy subjects at baseline and after 7 days of dapagliflozin treatment. A: TmG for all subjects. B: TmG for all 12 subjects with type 2 diabetes and 11 healthy subjects minus 1 outlier, which is shown separately.CC BY-NC-ND · PubMed Central
Figure 3 A: Relationship between urinary glucose secretion (mg per 40 min SHC) and target plasma glucose concentration in type 2 diabetic and healthy subjects before and after 7 days of dapagliflozin treatment. B: Percentage of the filtered glucose load appearing in the urine of type 2 diabetic and healthy subjects before and after 7 days of dapagliflozin treatment.
Figure 3 A: Relationship between urinary glucose secretion (mg per 40 min SHC) and target plasma glucose concentration in type 2 diabetic and healthy subjects before and after 7 days of dapagliflozin treatment. B: Percentage of the filtered glucose load appearing in the urine of type 2 diabetic and healthy subjects before and after 7 days of dapagliflozin treatment.CC BY-NC-ND · PubMed Central

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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
DOI
10.2337/dc13-0387
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
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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