SGLT2i demonstrated the strongest protective association against dementia in individuals with T2DM, according to a large meta-analysis published in Diabetes, Obesity and Metabolism.

The analysis included 67 trials involving more than 4 million participants and compared nine antidiabetic drug classes. Data from PubMed, Cochrane Library, and Igaku Chuo Zasshi-Web were reviewed through December 2023. SGLT2i, GLP-1 RAs, TZDs, and DPP-4 inhibitors were all associated with a reduced dementia risk compared with placebo, no treatment, or other glucose-lowering agents.

In contrast, insulin use was linked to an elevated dementia risk. Metformin, sulfonylureas, glinides, and α-glucosidase inhibitors showed no significant relationship with cognitive outcomes. Drug ranking placed SGLT2 inhibitors highest for dementia risk reduction, followed by GLP-1 RAs, TZDs, and DPP-4 inhibitors, with insulin ranked lowest.

These results highlight the potential of newer antidiabetic agents to provide cognitive benefits in addition to glucose control among individuals with T2DM.