Related Experiment Video

Updated: May 13, 2025

Glycemic Impact on Knee Osteoarthritis Symptoms on Physical, Radiographic, and Inflammatory Markers among Individuals Aged 50 and Over with Diabetes
07:22

Glycemic Impact on Knee Osteoarthritis Symptoms on Physical, Radiographic, and Inflammatory Markers among Individuals Aged 50 and Over with Diabetes

Published on: March 7, 2025

138

The Impact of SGLT-2 Inhibitors on Hydroxyl Radical Markers and Diabetic Neuropathy: A Short-Term Clinical Study

Ágnes Klabuzai1,2, Viktória Bekő1, Zsófia Sütő1

  • 12nd Department of Medicine and Nephrology-Diabetes Centre, University of Pécs Medical School, H-7624 Pécs, Hungary.

Antioxidants (Basel, Switzerland)
|April 14, 2025
PubMed

Insights

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors improve metabolic, hematologic, renal, and nerve function in type 2 diabetes patients. These effects are linked to reduced hydroxyl free radical production, suggesting a novel mechanism of action for SGLT-2 inhibitors.

Area of Science:

  • Endocrinology
  • Nephrology
  • Cardiology
  • Neurology

Background:

  • Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are known for metabolic benefits in type 2 diabetes.
  • Beyond glycemic control, SGLT-2 inhibitors demonstrate cardiovascular and nephroprotective effects.
  • The precise mechanisms underlying these pleiotropic effects remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of SGLT-2 inhibitor initiation on metabolic, hematologic, renal, and neuropathic parameters.
  • To explore the potential role of hydroxyl free radical production in mediating SGLT-2 inhibitor effects.
  • To examine correlations between oxidative stress markers and clinical outcomes.

Main Methods:

  • Prospective study of 40 type 2 diabetes patients initiating SGLT-2 inhibitor therapy.
  • Evaluated clinical and laboratory measurements, hydroxyl free radical markers (urinary tyrosine ratios), and neuropathic assessments (current perception threshold).
  • Measurements were taken before and 4 weeks after SGLT-2 inhibitor initiation.

Main Results:

  • Significant reductions in body weight, BMI, fasting glucose, fructosamine, and albuminuria.
  • Significant increases in RBC count, hemoglobin, hematocrit, MCV, and platelet count.
  • Reduced urinary o-tyrosine/p-tyrosine and (m-tyrosine+o-tyrosine)/p-tyrosine ratios, indicating diminished hydroxyl free radical production.
  • Significant improvement in neuropathic assessments (CPT) in patients with baseline neuropathy.
  • Disappearance of correlations between hematologic/renal markers and hydroxyl free radical markers post-treatment.
  • Changes in hydroxyl free radical markers correlated positively with CPT improvements.

Conclusions:

  • Short-term SGLT-2 inhibition simultaneously improves metabolic, hematologic, renal, and neuropathic endpoints in type 2 diabetes.
  • These benefits are potentially mediated by the attenuation of abnormal tyrosine incorporation into signaling proteins, leading to reduced hydroxyl free radical production.
  • Further research is needed to confirm long-term efficacy and explore adjunctive therapies like p-tyrosine supplementation.
Keywords:
SGLT-2 inhibitordiabetic kidney diseasediabetic neuropathyhydroxyl free radicalmeta-tyrosineortho-tyrosineplateletred blood cell

More Related Videos

Author Spotlight: Exploring the Impact of Reduced Resistance Exercise Volume on Metabolic Health06:13

Author Spotlight: Exploring the Impact of Reduced Resistance Exercise Volume on Metabolic Health

Published on: December 1, 2023

1.0K
Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

469

Related Concept Videos

Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
141
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
134
Oral Hypoglycemic Agents: Glinides01:06

Oral Hypoglycemic Agents: Glinides

Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively...
111
Oral Hypoglycemic Agents: Sulfonylureas01:17

Oral Hypoglycemic Agents: Sulfonylureas

Sulfonylureas are oral hypoglycemic agents utilized in treating type 2 diabetes. They are characterized by their unique sulfonylurea chemical structure. The family of sulfonylureas is divided into generations. First-generation sulfonylureas, including tolbutamide (Orinase), chlorpropamide (Diabinese), and tolazamide (Tolinase), trigger insulin release from pancreatic β cells and enhance peripheral tissues' insulin sensitivity. The second-generation members, such as glipizide...
163
Glucose Transporters01:27

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:
22.2K
Oral Hypoglycemic Agents: α-Glucosidase Inhibitors01:19

Oral Hypoglycemic Agents: α-Glucosidase Inhibitors

α-glucosidase inhibitors, including acarbose (Precose), miglitol (Glyset), and voglibose (Voglib) (primarily available in Asia), are drugs that control blood sugar levels by delaying the digestion of starch and disaccharides. They achieve this by inhibiting α-glucosidase enzymes in the intestine, which slow the absorption of carbohydrates in the intestine, which in turn leads to a prolonged release of the glucoregulatory hormone GLP-1 from intestinal L-cells.
Acarbose and miglitol are...
124