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Anti-diabetic combination therapy with pioglitazone or glimepiride added to metformin on the AGE-RAGE axis: a

Eugenio Ragazzi1, Silvia Burlina2, Chiara Cosma2

  • 1Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.

Frontiers in Endocrinology
|August 28, 2023
PubMed
Abstract

Insights

Two oral anti-diabetic drugs, pioglitazone and glimepiride, significantly reduced advanced glycation end products (AGEs) and the AGE/soluble form of receptor (s-RAGE) ratio in type 2 diabetes patients over 5 years. Pioglitazone showed a greater reduction in the AGE/s-RAGE ratio.

Area of Science:

  • Endocrinology and Metabolism
  • Cardiovascular Research
  • Nephrology

Background:

  • The ratio of advanced glycation end products (AGEs) to their soluble receptor (s-RAGE) is a proposed risk marker for renal and cardiovascular diseases.
  • Understanding the impact of oral anti-diabetic treatments on the AGE/s-RAGE ratio is crucial for managing diabetes-related complications.

Purpose of the Study:

  • To evaluate the influence of two oral anti-diabetic treatments, pioglitazone and glimepiride, on the AGE/s-RAGE ratio in patients with type 2 diabetes over a 5-year period.
  • To compare the efficacy of pioglitazone versus glimepiride in modulating the AGE/s-RAGE ratio.

Main Methods:

  • Seventy-three type 2 diabetes mellitus patients were randomized to receive either pioglitazone or glimepiride, both in combination with metformin.
  • Patients were assessed at baseline and after 5 years of treatment for AGE and s-RAGE levels.
  • The AGE/s-RAGE ratio was calculated and analyzed for significant changes.

Main Results:

  • Both pioglitazone and glimepiride treatments significantly reduced AGE levels and the AGE/s-RAGE ratio by over 50% after 5 years compared to baseline.
  • Soluble form of receptor (s-RAGE) levels did not significantly change in either treatment group.
  • Pioglitazone demonstrated a more significant reduction in the AGE/s-RAGE ratio compared to glimepiride after 5 years.

Conclusions:

  • Oral anti-diabetic therapy, particularly with pioglitazone, can improve endothelial function markers by reducing the AGE/s-RAGE ratio, potentially lowering cardiovascular risk.
  • The AGE-RAGE axis modulation suggests long-term benefits of pioglitazone in managing diabetes-related vascular complications.
Keywords:
AGEsadvanced glycation end productsglimepiridepioglitazones-RAGEtype 2 diabetes mellitus

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