Association Between SGLT2 Inhibitors and Risk of Dementia and Parkinson's Disease: A Meta-Analysis of 12 Randomized Controlled Trials

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been shown 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. Hence, we sought to evaluate the association between SGLT2i and the risk of dementia and Parkinson's disease in patients with type 2 diabetes mellitus, heart failure, or chronic kidney disease.

Methods: We performed a systematic literature search on PubMed, and Clinicaltrial.gov for relevant randomized controlled trials 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 randomized controlled trials with 74,442 patients (40,784 in the SGLT2i group and 33,658 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. Pooled analysis showed that there is no significant association between SGLT2i use and the risk of dementia (OR 1.37; 95% CI, 0.70-2.69; P = .36), dementia Alzheimer's type (OR 1.99; 95% CI, 0.59-6.71; P = .27), vascular dementia (OR 0.40; 95% CI, 0.09-1.85; P = .24), and Parkinson's disease (OR 0.63; 95% CI, 0.25-1.61; P = .33) when compared with the control groups.

Conclusion: Our study suggests that there is no significant association between SGLT2i use and the risk of dementia, its subtypes, and Parkinson's disease when compared with the control groups.