Abstract
Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years, primarily in highly developed Western societies. T2DM causes systemic complications, such as atherosclerotic heart disease, ischemic stroke, peripheral artery disease, kidney failure, and diabetes-related maculopathy and retinopathy. The growing number of T2DM patients and the treatment of long-term T2DM-related complications pressurize and exhaust public healthcare systems. As a result, strategies for combating T2DM and developing novel drugs are critical global public health requirements. Aside from preventive measures, which are still the most effective way to prevent T2DM, novel and highly effective therapies are emerging. In the spotlight of next-generation T2DM treatment, sodium-glucose co-transporter 2 (SGLT-2) inhibitors are promoted as the most efficient perspective therapy. SGLT-2 inhibitors (SGLT2i) include phlorizin derivatives, such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2, along with SGLT-1, is a member of the SGLT family of proteins that play a role in glucose absorption via active transport mediated by Na+/K+ ATPase. SGLT-2 is only found in the kidney, specifically the proximal tubule, and is responsible for more than 90% glucose absorption. Inhibition of SGLT-2 reduces glucose absorption, and consequently increases urinary glucose excretion, decreasing blood glucose levels. Thus, the inhibition of SGLT-2 activity ultimately alleviates T2DM-related symptoms and prevents or delays systemic T2DM-associated chronic complications. This review aimed to provide a more detailed understanding of the effects of SGLT2i responsible for the acute improvement in blood glucose regulation, a prerequisite for T2DM-associated cardiovascular complications control.
Keywords: Type 2 diabetes mellitus, T2DM, sodium-glucose transporter proteins, SGLT-2 inhibitors, cardiovascular complications, diabetes.
Current Medicinal Chemistry
Title:SGLT-2 Inhibitors: The Next-generation Treatment for Type 2 Diabetes Mellitus
Volume: 31 Issue: 30
Author(s): Nikola Lukic, Mirjana T. Macvanin, Zoran Gluvic, Manfredi Rizzo, Djordje Radak, Jasjit S. Suri and Esma R. Isenovic*
Affiliation:
- Department of Radiobiology and Molecular Genetics, VINČA Institute of Nuclear Sciences - National Institute of the Republic of Serbia, University of Belgrade, Belgrade, Serbia
Keywords: Type 2 diabetes mellitus, T2DM, sodium-glucose transporter proteins, SGLT-2 inhibitors, cardiovascular complications, diabetes.
Abstract: Type 2 diabetes mellitus (T2DM) has become a worldwide concern in recent years, primarily in highly developed Western societies. T2DM causes systemic complications, such as atherosclerotic heart disease, ischemic stroke, peripheral artery disease, kidney failure, and diabetes-related maculopathy and retinopathy. The growing number of T2DM patients and the treatment of long-term T2DM-related complications pressurize and exhaust public healthcare systems. As a result, strategies for combating T2DM and developing novel drugs are critical global public health requirements. Aside from preventive measures, which are still the most effective way to prevent T2DM, novel and highly effective therapies are emerging. In the spotlight of next-generation T2DM treatment, sodium-glucose co-transporter 2 (SGLT-2) inhibitors are promoted as the most efficient perspective therapy. SGLT-2 inhibitors (SGLT2i) include phlorizin derivatives, such as canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. SGLT-2, along with SGLT-1, is a member of the SGLT family of proteins that play a role in glucose absorption via active transport mediated by Na+/K+ ATPase. SGLT-2 is only found in the kidney, specifically the proximal tubule, and is responsible for more than 90% glucose absorption. Inhibition of SGLT-2 reduces glucose absorption, and consequently increases urinary glucose excretion, decreasing blood glucose levels. Thus, the inhibition of SGLT-2 activity ultimately alleviates T2DM-related symptoms and prevents or delays systemic T2DM-associated chronic complications. This review aimed to provide a more detailed understanding of the effects of SGLT2i responsible for the acute improvement in blood glucose regulation, a prerequisite for T2DM-associated cardiovascular complications control.
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Lukic Nikola, Macvanin T. Mirjana, Gluvic Zoran, Rizzo Manfredi, Radak Djordje, Suri S. Jasjit and Isenovic R. Esma*, SGLT-2 Inhibitors: The Next-generation Treatment for Type 2 Diabetes Mellitus, Current Medicinal Chemistry 2024; 31 (30) . https://dx.doi.org/10.2174/0109298673251493231011192520
DOI https://dx.doi.org/10.2174/0109298673251493231011192520 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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