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Sodium–Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport

Mudaliar, Sunder, Polidori, David, Zambrowicz, Brian, Henry, Robert R.·2015·Diabetes Care

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Abstract

Type 2 diabetes is a chronic disease with disabling micro- and macrovascular complications that lead to excessive morbidity and premature mortality. It affects hundreds of millions of people and imposes an undue economic burden on populations across the world. Although insulin resistance and insulin secretory defects play a major role in the pathogenesis of hyperglycemia, several other metabolic defects contribute to the initiation/worsening of the diabetic state. Prominent among these is increased renal glucose reabsorption, which is maladaptive in patients with diabetes. Instead of an increase in renal glucose excretion, which could ameliorate hyperglycemia, there is an increase in renal glucose reabsorption, which helps sustain hyperglycemia in patients with diabetes. The sodium-glucose cotransporter (SGLT) 2 inhibitors are novel antidiabetes agents that inhibit renal glucose reabsorption and promote glucosuria, thereby leading to reductions in plasma glucose concentrations. In this article, we review the long journey from the discovery of the glucosuric agent phlorizin in the bark of the apple tree through the animal and human studies that led to the development of the current generation of SGLT2 inhibitors.

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Authors: Mudaliar, S., Polidori, D., Zambrowicz, B., & Henry, R. R.
Affiliations: University of California San Diego (US)
Janssen Research & Development (United States) (US)
Regeneron (United States) (US)
Corresponding author: Mudaliar, Sunder
ORCID: Mudaliar, Sunder
Polidori, David
Zambrowicz, Brian
Henry, Robert R.
Venue: Diabetes Care
Publisher: American Diabetes Association
Published: 2015-11-19
Volume: 38
Issue: 12
Pages: 2344-2353
ISSN: 0149-5992 (ISSN-L)
1935-5548
DOI: 10.2337/dc15-0642
OpenAlex: W2175616918
Cited by: 225
References: 60
Citations by year: 2026: 5 · 2025: 19 · 2024: 14 · 2023: 18 · 2022: 21 · 2021: 21 · 2020: 23 · 2019: 17 · 2018: 27 · 2017: 32 · 2016: 28
FWCI: 4.36
Type: journal article
Language: en
Open access: closed
Locations: Diabetes Care (publishedVersion)
PubMed (publishedVersion)
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, sodium-glucose cotransporter, renal glucose reabsorption, intestinal glucose transport, type 2 diabetes, hyperglycemia, glycosuria, phloridzin, antidiabetic drug development, history of drug discovery
MeSH terms: Sodium-Glucose Transporter 2 Inhibitors, Animals, Biological Transport, Diabetes Mellitus, Type 2, Glucose, Glycosuria, Humans, Hypoglycemic Agents, Insulin Resistance, Intestinal Mucosa, Kidney, Phlorhizin, Sodium-Glucose Transport Proteins, Sodium-Glucose Transporter 2, Renal Elimination

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Sodium–Glucose Cotransporter Inhibitors: Effects on Renal and Intestinal Glucose Transport

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