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Comparative Analysis of Pioglitazone and Tirzepatide on Body Weight, Glucose Levels, Neuroinflammation, and Oxidative

Ahmad Alhowail1, Mohammed F Aldawsari2, Maha Aldubayan1

  • 1Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia.

Drug Design, Development and Therapy
|August 7, 2025
PubMed
Abstract

Insights

Tirzepatide (TZP) and pioglitazone (PIO) improved cognitive function in type 2 diabetes mellitus (T2DM) rats by reducing neuroinflammation and oxidative stress. Pioglitazone showed greater efficacy than tirzepatide in these neuroprotective effects.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) is linked to cognitive impairment due to inflammation and oxidative stress.
  • Existing T2DM medications like tirzepatide (TZP) and pioglitazone (PIO) may offer neuroprotective benefits.
  • Understanding these effects is crucial for managing diabetic cognitive decline.

Purpose of the Study:

  • To investigate the neuroprotective effects of TZP and PIO in a rat model of T2DM.
  • To assess their impact on mitigating neuroinflammation and oxidative stress.
  • To evaluate their efficacy in improving cognitive deficits associated with T2DM.

Main Methods:

  • T2DM was induced in male albino rats using streptozotocin and nicotinamide.
  • Rats were divided into groups: Saline, TZP, PIO, T2DM, T2DM+TZP, and T2DM+PIO.
  • Treatments lasted 15 days, followed by assessments of survival, body weight, cognitive function (Y-maze, NOR), glucose, inflammatory markers (TNF-α, IL-6, IL-1β), and oxidative stress biomarkers (SOD, GPx, MDA).

Main Results:

  • T2DM induction negatively impacted survival, body weight, and cognitive function, while increasing glucose levels, neuroinflammation, and oxidative stress.
  • Both TZP and PIO treatments improved survival rates and cognitive function in diabetic rats.
  • PIO demonstrated a more significant reduction in neuroinflammation and oxidative stress compared to TZP.

Conclusions:

  • TZP and PIO treatments effectively ameliorate cognitive impairment in T2DM.
  • Pioglitazone exhibits superior efficacy over tirzepatide in reducing neuroinflammation and oxidative stress in diabetic rats.
  • These findings highlight the potential of TZP and PIO as therapeutic agents for cognitive deficits in T2DM.
Keywords:
cognitive impairmentdiabetesinflammationinsulinoxidative stresspioglitazonetirzepatide

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