Impact of hypoglycemic agents on glycemic control and cognitive decline in older adults with type 2 diabetes: real-world evidence on glucagon like peptide 1 receptor agonists

BACKGROUND: Type 2 diabetes mellitus (T2DM) is frequently associated with cognitive decline in the older population. Although optimal glycemic control is known to be essential for disease management, the impact of hypoglycemic agents on cognitive function remains poorly investigated. METHODS: This retrospective study included 93 geriatric outpatients with T2DM. Hypoglycemic treatments consisted of metformin, sodium-glucose co-transporter 2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl peptidase-4 inhibitors, and insulin. Patient evaluations included glycated hemoglobin (HbA1c) measurements, Standardized Mini-Mental State Examination (MMSE), and Mini Nutritional Assessment (MNA). RESULTS: After one year of treatment, patients exhibited a significant reduction in HbA1c levels (from 8.06% [±1.19] to 7.19% [±0.84], P<0.001), improvement of MMSE scores (from 25.87 [±3.09] to 27.47 [±2.9], P<0.001). Regression analysis identified GLP-1RAs as the most effective agent in improving glycemic control (P<0.001) and cognitive function (P=0.016). Treatment with GLP-1RAs was associated with a reduction in MNA scores (P<0.001), though these remained above the malnutrition threshold. CONCLUSIONS: Our findings suggest that improved glycemic control may help slow cognitive decline in older patients with T2DM. Among the drug classes examined, GLP-1RAs showed the largest reductions in HbA1c and were linked to greater MMSE score gains.