Association between dapagliflozin and risk of dementia and Parkinson's disease: a subgroup analysis of a meta-analysis of randomized controlled trials.

Introduction: Dementia and Parkinson's disease (PD) are prevalent neurodegenerative disorders with substantial global health impacts. Emerging evidence suggests that SGLT2 inhibitors, such as dapagliflozin, may offer neuroprotective benefits. This study aims to evaluate dapagliflozin's association with risks of dementia and PD through a sub-analysis of a meta-analysis of randomized controlled trials (RCTs).

Evidence acquisition: This sub-analysis adhered to PRISMA 2020 guidelines and included RCTs from a prior meta-analysis focusing on dapagliflozin. Studies comparing dapagliflozin to placebo with reported dementia or PD outcomes were selected. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model. Heterogeneity was assessed using the I² statistic, and bias was evaluated with the Cochrane Risk of Bias 2 tool.

Evidence synthesis: Four RCTs met the inclusion criteria. For dementia, the pooled OR was 2.826 (95% CI: 0.264-30.229; I²=0%). For Alzheimer's-type dementia, the OR was 2.308 (95% CI: 0.232-22.928; I²=0%), while for PD, the OR was 0.533 (95% CI: 0.072-3.944; I²=0%). None of the results were statistically significant, and heterogeneity across studies was negligible.

Conclusions: This sub-analysis found no significant association between dapagliflozin and reduced risks of dementia or PD. While these results align with previous meta-analyses, further long-term RCTs are necessary to clarify dapagliflozin's neuroprotective potential and broader therapeutic applications.