Pioglitazone for Primary and Secondary Prevention of Cardiovascular and Renal Outcomes in Patients with or at High Risk of Type 2 Diabetes: A Meta-Analysis

Background: Type 2 diabetes mellitus (T2DM) is a global health challenge associated with significant cardiovascular and renal complications. Pioglitazone, a thiazolidinedione, has demonstrated potential in reducing adverse outcomes beyond glycemic control because of its insulin-sensitizing and anti-inflammatory qualities. However, its safety and efficacy remain subjects of ongoing research. Aim: To assess pioglitazone's safety and effectiveness in preventing cardiovascular and renal outcomes in individuals with or at high risk of type 2 diabetes, including primary and secondary. Methods: Using information from randomized controlled trials (RCTs) released between 2018 and 2024, a meta-analysis was performed. Methodical searches in the PubMed, Cochrane Library, and Embase databases turned up pertinent research. Cardiovascular and renal outcome data were extracted, and SPSS version 23.0 was used for statistical analysis. The I2 statistic was used to evaluate the heterogeneity of the studies. Results: The analysis included 120 participants from six RCTs. Pioglitazone significantly reduced the risk of major adverse cardiovascular events (20.0% vs. 33.3%, p = 0.032) and cardiovascular mortality (8.3% vs. 15.0%, p = 0.045). Renal disease progression was observed in 16.7% of the pioglitazone group compared to 30.0% in controls (p = 0.027). All-cause mortality was lower in the pioglitazone group (10.0% vs. 18.3%, p = 0.048). Moderate heterogeneity was noted across studies (I² = 45%-50%). Adverse effects such as edema and weight gain were reported but did not outweigh the clinical benefits in selected patients. Conclusion: Pioglitazone helps people with or at high risk of type 2 diabetes by lowering cardiovascular and renal consequences. Its benefits extend beyond glycemic control, particularly in high-risk populations. However, potential adverse effects necessitate individualized treatment plans. Recommendations: Future studies ought to concentrate on long-term results, the best ways to dose medications, and reducing side effects. Clinical guidelines should emphasize personalized medicine to maximize the benefits of pioglitazone while mitigating risks. Keywords: Pioglitazone, Type 2 Diabetes Mellitus, Cardiovascular Outcomes, Renal Protection, Meta-Analysis