Endocrine Abstracts

Background and aim: Acute and chronic brain dyscirculation comprise one of the main reasons of death and disability in type 2 diabetes. Glucose-lowering drugs of glucagon-like peptide-1 receptor agonists (GLP-1RA) group have proved to decrease myocardial infarction and stroke incidence, nevertheless their influence on chronic brain damage in not fully studied. Taking into account existing guidelines recommending treatment with GLP-1RA even for patients with satisfactory glycemic control, our aim was to study the influence of semaglutide in type 2 diabetic patients with target glycated hemoglobin (HbA1c) level on cognitive function and circulating neuronal damage markers.

Materials and methods: Type 2 diabetic patients aged 45-75 with target HbA1c (6.7[6.6;6.9]%) on metformin monotherapy were randomly divided into two groups: ‘MET’ (n=28) – those who continued metformin monotherapy, and ‘SEMA’ (n=35) – patients who were co-administered semaglutide (Rybelsus, Novo Nordisk) for 6 months. Additionally, ‘Control’ (n=30) group was formed – healthy volunteers comparable by age and gender. In all groups the levels of HbA1c, neuron-specific enolase (NSE), neurofilament light chains (NLC) were determined initially, cognitive assessment was performed by MOCA and MMSE scores. In ‘SEMA’ group these parameters were also evaluated 3 and 6 months after.

Results: Baseline NSE level in diabetic patients was higher than in healthy volunteers despite satisfactory glycemic control (3.60 [3.19;3.78] ng/ml in ‘MET’ and 3.78 [3.05;4.32] ng/ml in ‘SEMA’ groups and 2.76 [2.28;3.30] ng/ml in ‘Control’ group). Similarly baseline NLC concentration was high in both ‘MET’ and ‘SEMA’ groups than in ‘Control’ one (4.95 [3.30;5.56] ng/ml, 5.25 [3.75;5.56] and 4.10 [3.27;5.30 ]ng/ml, respectively). HbA1c decreased in ‘SEMA’ group, though not significantly, remaining in the target range. NSE concentration decreased in ‘SEMA’ group in 3 months (2.95 [2.42;3.4] ng/ml) and remained normal in 6 months (2.93 [2.58; 3.33] ng/ml). NLC also decreased in ‘SEMA’ group in 3 months (4.25 [3.13;8.50] ng/ml and even more prominently in 6 months (3.50 [1.69;5.88] ng/ml). Patients in ‘MET’ and ‘SEMA’ groups had cognitive impairment, resulting in the decreased points by both MOCA and MMSE scales. SEMA administration led to cognitive 4improvement – by 6th month of therapy MOCA scores in ‘SEMA’ group was 27.5 [25.75;29.75] (the normal value is 26 and more) and MMSE scores was 29.0 [27.5;29.5] (the normal value is 28-30). We found negative correlation between NLC level and MOCA, MMSE scores (r=-0.512, р=0.005 и r=-0.703, р=0.000, respectively).

Conclusions: DM, even with satisfactory glycemic control, has a negative impact on the brain, which is manifested by neuronal damage markers increase and cognitive dysfunction. Semaglutide can be neuroprotective in diabetic chronic brain damage independently on glycemic control.