Metformin, SGLT2is confer protection against dementia

Among various glucose-lowering medications, metformin and sodium glucose co-transporter-2 inhibitors (SGLT2is) are associated with a reduced risk of dementia, as shown in the results of a meta-analysis.

Researchers searched multiple online databases for observational studies wherein the incidence of dementia and Alzheimer’s disease (AD) was examined in relation to the initiation of glucose-lowering medications.

The Preferred Reporting Items for Systematic Reviews-Network Meta-Analyses (PRISMA-NMA) guidelines were followed, and Bayesian network meta-analysis was performed.

A total of 16 studies, which involved 1,565,245 individuals, met the eligibility criteria and were included in the meta-analysis. Pooled data showed that both dementia and AD risks were significantly lower among metformin and SGLT2i initiators.

The lowest risk of dementia was seen among metformin initiators, whereas the highest risk was recorded among initiators of α-glucosidase inhibitors. Among glucose-lowering medications used in the second-line setting, SGLT2i was associated with the lowest dementia risk.

In the subgroup of older adults at least 75 years of age, those who initiated dipeptidyl peptidase-4 inhibitor (DPP4i), metformin, sulfonylureas, and thiazolidinediones had a significantly increased risk of dementia compared with those who initiated SGLT2is.

Meanwhile, among metformin initiators, the risk of dementia was substantially lower, regardless of diabetic complication status or baseline A1C.

The researchers advised cautious interpretation of the findings, pointing out that patient-specific factors may affect the observed relationships, with metformin typically initiated at an earlier stage when there are fewer complications. Therefore, additional large-scaled clinical trials are warranted.