Scientific Poster Session III - Original Research

Original Research
  Monday, November 13, 2023
  01:00 PM–02:30 PM

Abstract

Introduction: It is becoming widely accepted that cognitive impairment is one of the complications of type 2 diabetes mellitus (T2DM). Thus far, disease-modifying therapeutic interventions in cognitive disorders are not forthcoming. However, there is mounting interest in the neuroprotective action of some anti-diabetic drugs, such as dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose cotransporter-2 inhibitors (SGLT2i).

Research Question or Hypothesis: We hypothesize that combining DPP-4i and/or SGLT2i with metformin will reduce cognitive deterioration in T2DM patients.

Study Design: We conducted a cross-sectional study, where we compared T2DM patients on DPP-4i or SGLT2i in combination with metformin with a control group receiving metformin monotherapy. Moreover, a group of healthy subjects were recruited as a baseline reference.

Methods: For each patient recruited, a detailed patient profile was filled in, cognitive function was assessed using a validated Arabic version of the Montreal Cognitive Assessment (MoCA), and blood samples were collected to assess glucose control and inflammatory markers (CRP and IL-6) levels. Furthermore, metabolomic screening and pathway analysis were performed on the collected serum samples. One-way ANOVA was conducted for statistical analysis using GraphPad Prism. A P-value <0.05 was considered significant.

Results: Patients on metformin monotherapy had a significantly lower MoCA score than healthy volunteers, however, there was no significant difference between healthy volunteers and patients in the combination groups. This effect was not linked to glycemic control nor related to a reduction of typical inflammatory mediators measured. Furthermore, in comparison to healthy volunteers, patients on metformin monotherapy showed elevated D-amino acids through the metabolomic analysis conducted and showed an upregulation of the ribonucleosides degradation to ribose-1-phosphate pathway.

Conclusion: DPP-4i and SGLT2i in combination with metformin in comparison to metformin monotherapy might offer a cognitive protective effect through pathways other than glycemic control and systemic inflammation. Neuroprotection could be attributed to DPP-4i and SGLT2i overall impact on D-amino acids metabolism and changes in nucleoside metabolism.

Presenting Author

Shams T. Osman BPharm
Faculty of Pharmacy, Alexandria University

Authors

Mahmoud A. Agami PhD
Faculty of Pharmacy, New Valley University

Yehia Mechref PhD
Texas Tech University

Mona Goli PhD
Texas Tech University

Noha A. Hamdy PhD
Faculty of Pharmacy, Alexandria University

Waziha Purba BSc
Texas Tech University

Amr Y. El-Feky PhD
Faculty of Medicine, Alexandria University

Labiba K. El-Khordagui PhD
Faculty of Pharmacy, Alexandria University

Ahmed F. El-Yazbi PhD
Faculty of Pharmacy, Alexandria University and Alamein International University

Junyao Wang PhD
Texas Tech University