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Diabetes Care. 2013 Oct;36(10):3169-76. doi: 10.2337/dc13-0387. Epub 2013 Jun 4.

Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes.

Author information

1
Corresponding author: Ralph A. DeFronzo, albarado@uthscsa.edu.

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.

PMID:
23735727
PMCID:
PMC3781504
DOI:
10.2337/dc13-0387
[Indexed for MEDLINE]
Free PMC Article
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