Drug Repositioning of Pioglitazone in Management and Improving the Cognitive Function among the Patients with Mild to Moderate Alzheimer's Disease: A Systematic Review and Meta-Analysis

• Published in: Neurology India 2023-11, Vol.71 (6), p.1132-1141
• Main Authors: Basutkar, Roopa, Sudarsan, Pooja, Robin, Sandra, Bhaskar, Vahini, Viswanathan, Balasubramaniam, Sivasankaran, Ponnusankar
• Format: Article
• Language: English
• Subjects: Advertising executives; Alzheimer's disease; Clinical trials; Cognitive ability; Drug therapy; Evaluation; Hypoglycemia; Pharmaceutical research
• ISSN: 0028-3886; 1998-4022
• DOI: 10.4103/0028-3886.391397

Background: Disease-modifying agents like Pioglitazone have shown promising effects on neuroinflammation and homeostasis of amyloid plaques, but there is a lack of research papers providing conclusive evidence. Objectives: This study is aimed to determine the safety and efficacy of Pioglitazone in improving cognitive function in patients with mild-moderate Alzheimer's disease (AD). Materials and Methods: Trials published in the last 12 years were identified from PubMed, Scopus, Cochrane Central, and other trial registries. Five hundred twenty-five records were obtained, from which five studies were included for quantitative analysis. Studies comparing Pioglitazone with a suitable placebo or other oral hypoglycemic agent were considered for review. Data was extracted using a pretested form, which was followed by a risk of bias assessment (ROB) with Cochrane's ROB assessment tool. Results: This meta-analysis included studies where Pioglitazone (15–30 mg) was compared to other oral hypoglycemic agents, placebo, or diabetic diet for a minimum duration of 6 months. Pioglitazone did not show a statistically significant improvement in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores [mean difference (MD): −1.16; 95% confidence interval (CI): −4.14–1.81]. By conducting sensitivity analysis with the removal of one study, significant efficacy was obtained [MD: −2.75; 95% CI: −4.84–−0.66]. The Wechsler Memory Scale-Revised logical memory I (WMS-R) scores had a significant improvement in the Pioglitazone group [MD: 2.02; 95% CI: 0.09–3.95]. Conclusion: Pioglitazone is a safe medication that has a promising effect in slowing the advancement of AD.