Abstract Body (Do not enter title and authors here):


Background
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have demonstrated to reduce the risk of hospitalizations from heart failure and cardiovascular mortality. However, SGLT2i therapy’s potential effects on the risks of dementia and Parkinson’s disease are not well established, with conflicting results based on observational studies.

Objective
We sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson’s disease in patients with type 2 diabetes mellitus (T2DM), heart failure, or chronic kidney disease.

Methods
We performed a systematic literature search on PubMed, Scopus, and Clinicaltrial.gov for relevant randomized controlled trials (RCTs) from inception until March 2024 without any language restrictions. Odds ratios (OR) and 95% confidence intervals (CI) were pooled using a random-effect model.

Results
A total of 12 RCTs with 74, 442 patients (40784 in the SGLT2i group and 33658 in the control group) were included in the analysis. The mean age of patients in SGLT2i and control was 65.3 and 65.2 years respectively. The mean follow-up duration was 2.9 years. Pooled analysis showed that there is no significant association between SGLT2i and the risk of dementia (OR, 1.37 (95%CI: 0.70-2.69), P=0.36, I2=0%), dementia Alzheimer’s type (OR, 2.62 (95%CI: 0.47-14.49), P=0.27, I2=0), vascular dementia (OR, O.52 (95%CI: 0.09-2.98), P=0.46, I2=0%), and Parkinson’s disease (OR, 0.75 (95%CI: 0.25-2.25), P=0.61, I2=0%) was comparable between SGLT2i and control groups.

Conclusion
Our study suggest that there is no significant association between SGLT2i and the risk of dementia, its subtypes, and Parkinson’s disease. Further large-power randomized trials are needed to strengthen the understanding of neuropsychiatric beneficial effects of SGLT2i.