Annals of Internal MedicineSodium–Glucose Cotransporter-2 Inhibitors, Dulaglutide, and Risk for Dementia: A Population-Based Cohort Study

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This study compares the risk of dementia in older patients with type 2 diabetes who were treated with either sodium–glucose cotransporter-2 (SGLT2) inhibitors or dulaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA). The research, conducted using South Korean national health data, aimed to evaluate the potential neuroprotective effects of these medications in preventing dementia.

Study Design:

• Target trial emulation study using nationwide health care data from South Korea (2010-2022)
• Included patients aged 60 years or older with type 2 diabetes initiating SGLT2 inhibitors or dulaglutide
• 1:2 propensity score–matched cohort adjusted for confounders
• Primary outcome: presumed clinical onset of dementia (defined as 1 year before diagnosis date)
• Median follow-up of 4.4 years

Key Findings:

• 12,489 patients initiated SGLT2 inhibitor treatment (51.9% dapagliflozin, 48.1% empagliflozin)
• 1,075 patients initiated dulaglutide treatment
• Primary outcome occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group
• Estimated risk difference: -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point)
• Estimated risk ratio: 0.81 (CI, 0.56 to 1.16)

HCN Medical Memo
Although this study provides valuable insights into the potential neuroprotective effects of SGLT2 inhibitors and dulaglutide, the results are not definitive. The wide confidence intervals and limitations in study design warrant cautious interpretation. Clinicians should consider these findings in the context of individual patient factors and await further research, particularly studies including newer GLP-1 RAs, before making significant changes to prescribing practices for dementia prevention in type 2 diabetes patients.

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