Cognitive Protective Effect of Newer Antidiabetic Drugs

Investigating the Protective Effect of Newer Antidiabetic Drugs on Cognitive Decline in Diabetic Patients

The proposed study aims to:

1. Explore the cognitive protective effects of SGLT2 inhibitors and DPP-4 inhibitors in patients attending diabetic clinics in Alexandria
2. Examine the possible relationship of such effects with the systemic inflammatory and metabolic status in these patients
3. Undertake a network analysis to elucidate the potential pathways linking the observed protective effects, if any, with the observed changes in inflammatory or metabolic parameters

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Empagliflozin; Drug: Canagliflozin; Drug: Sitagliptin; Drug: Saxagliptin; Drug: Linagliptin; Drug: Vildagliptin

Detailed Description

The investigators propose to profile diabetic patients taking SGLT2 inhibitors and DPP-4 inhibitors using different parameters and compare them to others on more traditional anti-diabetic therapy. Regression and comparative statistics will be used to determine whether the targeted drug classes offer a benefit in terms of cognitive function. If a trend (or correlation) is determined, a bioinformatic approach will be adopted to perform a network analysis including the targets of these drug classes and pathways showing in datasets of the inflammatory or metabolic parameters altered by the drug. This network analysis is intended to provide further mechanistic insight into the pathways involved in the observed drug action.

The patients targeted will be divided into the following groups:

1. Diabetic patients treated with metformin and DPP-4 inhibitors and/or SGLT2 inhibitors
2. Diabetic patients treated with metformin only

This will be in addition to a group of healthy non-diabetic controls to serve as a baseline reference.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Shams T Osman, BPharm; Phone Number: +201096900070; Email: s-shams.mostafa@alexu.edu.eg
• Study Contact Backup: Name: Ahmed F El-Yazbi, PhD; Phone Number: +201155881772; Email: ahmed.fawzy.aly@alexu.edu.eg

Study Locations

• Egypt
  • Alexandria, Egypt
    • Recruiting
    • Alexandria University
    • Contact: Shams T Osman, BPharm; Phone Number: +201096900070; Email: s-shams.mostafa@alexu.edu.eg
    • Contact: Ahmed F El-Yazbi, PhD; Phone Number: +201155881772; Email: ahmed.fawzy.aly@alexu.edu.eg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Diabetic patients receiving care in diabetes ambulatory clinics in Alexandria

Description

Inclusion Criteria:

• Type 2 Diabetic Patients
• Age (≥50 Years)
• Ability to understand and cooperate with study procedures

Exclusion Criteria:

• Diagnosed dementia
• Use of possible or known cognition impairing drugs in the last three months

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
New Antidiabetic; Type 2 diabetic patients receiving SGLT2 inhibitors and/or DPP-4 inhibitors with metformin	Drug: Dapagliflozin; usual and customary doses for type 2 diabetes management; Drug: Empagliflozin; usual and customary doses for type 2 diabetes management; Drug: Canagliflozin; usual and customary doses for type 2 diabetes management; Drug: Sitagliptin; usual and customary doses for type 2 diabetes management; Drug: Saxagliptin; usual and customary doses for type 2 diabetes management; Drug: Linagliptin; usual and customary doses for type 2 diabetes management; Drug: Vildagliptin; usual and customary doses for type 2 diabetes management
Traditional Antidiabetic; Type 2 diabetic patients treated with metformin
Control; Healthy non-diabetic patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevention of decline in cognitive function associated with type 2 diabetes	Slowed reduction of the Montreal Cognitive Assessment Battery Score	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Better cognitive performance in the intervention group at baseline	Higher Montreal Cognitive Assessment Battery Score	1 Year

Other Outcome Measures

Outcome Measure	Time Frame
Reduced serum inflammatory markers in intervention group	1 Year

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Ahmed F El-Yazbi, PhD, Professor of Pharmacology and Therapeutics, Alexandria University; Principal Investigator: Labiba El-Khordagui, PhD, Professor of Pharmaceutics, Alexandria University; Principal Investigator: Amr El-Feky, MD, Assistant Professor of Internal Medicine, Alexandria University; Principal Investigator: Shams T Osman, BPharm, Instructor of Clinical Pharmacy, Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): March 2, 2022
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: January 20, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 26, 2022

Study Record Updates

• Last Update Posted (Actual): July 26, 2022
• Last Update Submitted That Met QC Criteria: July 24, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Sodium-Glucose Transporter 2 Inhibitors; Dipeptidyl-Peptidase IV Inhibitors; Dapagliflozin; Empagliflozin; Linagliptin; Sitagliptin Phosphate; Vildagliptin; Canagliflozin; Saxagliptin
• Other Study ID Numbers: DIAB-DRUG-COG-FUN-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: After publication a link will be provided for a data repository folder
• IPD Sharing Time Frame: Data will be come available after publication and remain available indefinitely
• IPD Sharing Access Criteria: Anyone who wishes to access the data
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No