Comparative evaluation of SGLT-2i and GLP-1RA neuroprotective properties in type 2 diabetic patients

BACKGROUND: Chronic brain dyscirculation (CBD) is a common type 2 diabetes mellitus (DM) complication that leads to the cognitive dysfunction. Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter type 2 inhibitors (SGLT-2i) can reduce the stroke risk but their effect on CBD is not fully studied.

AIM: To study and to compare the effect of SGLT-2i of various selectivity and GLP-1RA on the biochemical and functional parameters of CNS damage in patients with type 2 DM.

MATERIALS AND METHODS: Type 2 diabetic patients with target HbA1c level on metformin monotherapy were included in “MET” group (n=43), with non-target HbA1c were divided into groups: “MET+EMPA”, n=47, (empagliflozin therapy), “MET+CANA”, n=41, (canagliflozin therapy), “MET+GLP-1RA”, n=66 (therapy with injectable GLP-1RA). The “Control” group (n=23) consisted of healthy volunteers. In “Control” and “MET” groups at baseline, in the rest groups also after 3 and 6 months neuron-specific enolase (NSE), neurofilament light chains (NLC) levels and cognitive status were determined.

RESULTS: NSE was increased in all DM patients. GLP-1RA therapy did not lead to NSE decrease. NSE decreased in “MET+EMPA” group after 3 months and in “MET+CANA” group after 6 months. NLC levels were elevated in patients with non-target HbA1c compared to “Control”. Both SGLT-2i caused a more pronounced decrease in LCN than GLP-1RA after 3 months; after 6 months NLC in all treatment groups did not differ from “Control” group. At baseline all DM patients had impaired cognitive function according to MOCA and MMSE. Empagliflozin treatment resulted in the improvement, but not normalization, of cognitive status by MOCA scale. Canagliflozin led to cognitive function normalization after 3 months and retention of the effect. GLP-1RA use was associated with mental function normalization after 6 months. Satisfactory glycemic control was achieved in all groups.

CONCLUSION: Type 2 DM is characterized by CNS damage even with satisfactory glycemic control. GLP-1RA and SGLT-2i have a protective effect in CBD in DM; the protective potential of low-selective canagliflozin is probably more pronounced, as it manifests in biochemical and functional parameters improvement. The neurotropic effect of GLP-1RA and SGLT-2i is not due solely to their effect on the glycemic profile.

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