Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans
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Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.
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SGLT2 inhibitors decrease reabsorption of glucose in the kidney and lower FPG and A1C, enhancing urinary glucose elimination and attenuating blood glucose level.
“In addition, Sodium-Glucose Cotransporter (SGLT) 2 Inhibitors are one of the latest pharmacological interventions to decrease the reabsorption of glucose in kidney and lower FGP and A1C, which enhances urinary glucose elimination and attenuates blood glucose level.”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [194]
SGLT2 inhibitors can positively affect cardiovascular diseases due to sodium decrease, uric acid absorption, and blood pressure reduction.
“Meanwhile, they can also positively affect cardiovascular diseases due to sodium decrease, uric acid absorption, and blood pressure reduction (194).”
From Diabetes and Sarcopenic Obesity: Pathogenesis, Diagnosis, and Treatments (2020) · cites this paper as [194]
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- Authors
- List, J. F., & Whaley, J. M.
- Affiliations
- Bristol-Myers Squibb (United States) (US)
- Corresponding author
- Whaley, Jean M.
- ORCID
- Whaley, Jean M.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 79
- Issue
- 120
- Pages
- S20-S27
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2077519024
- Cited by
- 184
- References
- 35
- Citations by year
- 2026: 11 · 2025: 10 · 2024: 7 · 2023: 7 · 2022: 16 · 2021: 14 · 2020: 13 · 2019: 13 · 2018: 3 · 2017: 10 · 2016: 19 · 2015: 19 · 2014: 16 · 2013: 16 · 2012: 8
- FWCI
- 1.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Kidney International (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- AstraZeneca
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- SGLT2 inhibitors, SGLT2, glucose reabsorption, proximal tubule, type 2 diabetes, urinary glucose excretion, glycemic control, insulin sensitivity, beta-cell function, weight loss, blood pressure reduction, dapagliflozin, pharmacokinetics, once-daily dosing, HbA1c
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Animals, Diabetes Mellitus, Type 2, Glucose, Humans, Hypoglycemic Agents, Insulin Resistance, Kidney Tubules, Proximal, Insulin-Secreting Cells
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