Antidiabetic agents and dementia risk in type 2 diabetes: A systematic review and network meta‐analysis

AIMS: Certain antidiabetic agents may prevent dementia in patients with type 2 diabetes mellitus (T2DM). The purpose of this study is to elucidate the relative effect of antidiabetic agents on reducing dementia risk in patients with T2DM. MATERIALS AND METHODS: PubMed, Cochrane Library and Igaku Chuo Zasshi-Web from inception to 31 December 2023 were searched. Trials reported in English or Japanese language that assessed the effects of glucose-lowering drugs on dementia were selected. RESULTS: Overall, 67 trials (4 088 683 individuals) assessing nine antidiabetic agent classes were included. Studies comprised monotherapies versus control (no use of antidiabetic agents or placebo) (three trials), monotherapies versus add-on therapies (one trial) and real-world database studies (63 trials). The analysis showed that the risk of dementia decreased with sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP1-RA), thiazolidinediones (TZD) and dipeptidyl peptidase-4 inhibitors (DPP4i) compared with the reference (placebo, no use of antidiabetic agents or other antidiabetic agents). Conversely, insulin was associated with an increased risk of dementia, whereas no significant association was found with the use of metformin, sulfonylureas, glinides and α-glucosidase inhibitors. Analyses of treatment rankings further revealed the relative effect on reducing dementia risk in the following order: SGLT2i > GLP1-RA > TZD > DPP4i; insulin ranked the lowest. CONCLUSIONS: The most effective antidiabetic agent in reducing dementia risk in T2DM is SGLT2i, followed by GLP1-RA, TZD and DPP4i, whereas insulin is associated with an elevated risk of dementia.