Objective:

This systematic review and meta-analysis aimed to evaluate the effect of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on cognition in patients with T2DM.

Background:

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have protective effects on cardiovascular and renal outcomes in patients with or without type 2 diabetes (T2DM). While animal studies have shown potential cognitive benefits of SGLT2i, evidence from human studies remains inconclusive.

Design/Methods:

A systematic search of PubMed and EMBASE was performed from inception to March 18, 2023, using prespecified keywords. Eligible studies compared the use of SGLT2i versus non-SGLT2i controls and reported the dementia outcomes. Safety outcomes included hypoglycemia and infection. Random-effects estimation based on Mantel-Haenszel method was used to calculate pooled relative risks with 95% confidence intervals. Forest and funnel plots were constructed.

Results:

Six observational studies involving 460,112 non-demented patients with T2DM were included. Of these, 155,844 patients received SGLT2i, and 304,268 patients received non-SGLT2i controls with a median follow-up of 2.8 years (range 1.3 to 11.4 years). The mean age of patients receiving SGLT2i was 71 years (range 61 to 80) similar to the control group 68 years (59 to 80). The incidence of dementia was 2.7% (4,202/155,844) in the SGLT2i group and 8.7% (26,366/304,268) in the control group (RR 0.50; CI 0.37-0.66; P<0.001). No significant difference in infection was observed between groups.

Conclusions:

SGLT2 inhibitors are associated with a significant reduction in the risk of dementia in patients with T2DM. These findings suggest that SGLT2 receptor may be a promising therapeutic target for the prevention of dementia in this population.