IMPACT OF SEMAGLUTIDE IN PATIENTS WITH TYPE 2 DIABETES AND MILD COGNITIVE IMPAIRMENT (MCI): clinical effects and genetic predictors of response

The study analyzed the effect and efficacy of semaglutide on cognitive function and neurophysiological parameters in a sample of patients with type 2 diabetes (T2DM) and mild cognitive impairment (MCI). The primary objective was to evaluate the impact of semaglutide on cognitive performance and on type 2 diabetes-related comorbidities, such as cognitive impairment and depression. A total of 72 patients (both sexes), aged 50 years or older, with T2DM and MCI were enrolled. Recruitment occurred between January 1, 2021, and December 31, 2023, spanning a total of 24 months. Patients were assessed at baseline (T0) and then every six months, for a total of five outpatient visits. Three single nucleotide polymorphisms (SNPs) associated with the risk of developing dementia - rs429358 (ApoE), and rs1467967 and rs2471738 (MAPT) - were investigated in order to identify potential genetic predictors of neurocognitive response to treatment with semglutide. For the neuropsychological assessment, tests such as the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), and Beck Depression Inventory (BDI) were used. The results showed a statistically significant improvement in neuropsychological test scores, indicating that semaglutide therapy is associated with enhanced cognitive performance. None of the SNPs under investigation demonstrated the ability to predict the neurocognitive response to treatment with semaglutide. In this study, Semaglutide appeared to have positive effects on T2DM-related comorbidities, helping to slow the progression of depression and impairments in mentalization.