Efficacy and Safety of Canagliflozin in the Treatment of Type 2 Diabetes With Mild Cognitive Impairment

Efficacy and Safety of Canagliflozin in the Treatment of Type 2 Diabetes With Mild Cognitive Impairment- a Prospective, Randomized, Single-blind, Controlled, Single-center, Head-to-head Clinical Cohort Study

The prevalence of cognitive dysfunction in diabetic patients is high, which seriously affects the quality of life of patients, and early intervention is of great significance. Central nervous system insulin resistance plays a key role in the pathogenesis of cognitive dysfunction in diabetic patients. Central insulin resistance observed by functional magnetic resonance imaging (fMRI), may serve as an alternative endpoint for assessing cognitive function. Sodium glucose cotransporter 2 inhibitor (SGLT2i) may improve cognitive impairment by improving central insulin resistance.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes Mellitus; Cognitive Impairment
• Intervention / Treatment: Drug: Canagliflozin group; Drug: Sitagliptin; Drug: Acarbose

Detailed Description

The prevalence of cognitive dysfunction in diabetic patients is high, which seriously affects the quality of life of patients. Cognitive impairment mainly includes two stages: mild cognitive impairment (MCI) and dementia. Early detection of diabetic patients with MCI and effective intervention measures to prevent and delay the onset of dementia have important clinical value and social significance. With the development of imaging technology, especially fMRI changes in local blood flow and metabolic activities of the brain can be displayed before changes in brain structure. The central insulin resistance status observed by fMRI may serve as an alternative endpoint for assessing cognitive function. SGLT2i has been shown to significantly improve insulin resistance in the central nervous system in previous basic and clinical studies. However, up to now, no head-to-head clinical studies have been reported on SGLT2i and other antidiabetic drugs in patients with MCI.

Based on the above research background, we hypothesize that canagliflozin, as a clinically commonly used SGLT2i, it may improve cognitive function in patients with type 2 diabetes mellitus and MCI by improving insulin resistance in the central nervous system.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Bin Lu, doctor; Phone Number: 18121186716; Email: lubinfd@126.com
• Study Contact Backup: Name: Cuiping Jiang, master

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China
      • Recruiting
      • Fudan University affiliated Huadong Hospital
      • Contact: Bin Lu, doctor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• age: 40-75 years old;
• HbA1c: 7.0 - 10.0%;
• Moca scale total score between 20-26 (duration of education is more than 10 years) or total score between 20 and 25 (duration of education is less than 10 years);
• sign informed consent;

Exclusion Criteria:

• left-handedness;
• duration of diabetes is less than 6 years;
• inability to complete central nervous system magnetic resonance imaging;
• alcohol or drug addiction history;
• use of other oral hypoglycemic drugs within 90 days prior to enrollment except for metformin;
• Family or past history of neurological or psychiatric disorders, pancreatitis, medullary thyroid cancer and multiple endocrine adenomatosis;
• History of recurrent urinary tract infection and malignant tumor;
• History of severe gastrointestinal diseases and gastroenteric surgery;
• Pregnancy/lactation status;
• Abnormal liver function (liver enzyme index is more than 2.5 times the upper limit of the reference range) or abnormal kidney function (estimated glomerular filtration rate is less than 45ml/min); Type 1 diabetes; other diseases or conditions that reduce the possibility of enrollment or complicate enrollment, such as frequent changes in the working environment and unstable living environment, which are likely to cause loss of follow-up, according to the judgment of the researchers;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: canagliflozin treatment group; Canagliflozin was used once daily, 100 mg/time, orally	Drug: Canagliflozin group; Canagliflozin,100mg once daily, orally, for 6 months
Placebo Comparator: sitagliptin treatment group; Sitagliptin was used 100mg once daily, orally.	Drug: Sitagliptin; Sitagliptin,100mg once daily, orally, for 6 months
Placebo Comparator: Acarbose treatment group; Acarbose was used 100mg three times daily, orally.	Drug: Acarbose; Acarbose,100mg three times daily, orally, for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the changes in cerebral blood flow shown by fMRI	the changes in cerebral blood flow shown by fMRI after nasal inhalation of insulin	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment Scale (Moca scale)	The Moca scale score ranges from 0 to 30. The higher the score, the better the cognitive function. Scores ranging from 12 to 21 are classified as dementia, while scores between 19 and 26 are classified as MCI. The investigators compare the scores of the Moca scale before and after the intervention.	6 months
body composition	The body composition is measured using Beijing Yueqi BIA. The indicators include weight (kg), skeletal muscle (kg), body fat (kg), body mass index (kg/m2), body fat percentage (%), visceral fat area (cm2), waist-to-hip ratio, and skeletal muscle index (kg/m2). The investigators compare the changes in body composition before and after the intervention.	6 months
grip strength	The grip strength is evaluated using an electronic grip strength tester. Each hand is tested twice, and the average values are taken. The side with the greater grip strength is selected as the final grip strength. A low grip strength is defined as less than 28 kg for men and less than 18 kg for women. The investigators compare the changes in grip strength before and after the intervention.	6 months
glycated hemoglobin	The glycated hemoglobin (%) is measured on an empty stomach, and the investigators compare the changes before and after the intervention.	6 months
insulin	The measurement of insulin (mIU/L) is conducted in the fasting state. The investigators compare the changes before and after the intervention.	6 months
C-peptide	The measurement of C-peptide (ng/ml) is conducted in the fasting state. The investigators compare the changes before and after the intervention.	6 months
blood glucose	The measurement of blood glucose (mmol/L) is conducted in the fasting state. The investigators compare the changes before and after the intervention.	6 months

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): October 30, 2026

Study Registration Dates

• First Submitted: February 2, 2024
• First Submitted That Met QC Criteria: July 14, 2026
• First Posted (Actual): July 17, 2026

Study Record Updates

• Last Update Posted (Actual): July 17, 2026
• Last Update Submitted That Met QC Criteria: July 14, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Mental Disorders; Metabolic Diseases; Neurocognitive Disorders; Glucose Metabolism Disorders; Diabetes Mellitus; Cognition Disorders; Nutritional and Metabolic Diseases; Cognitive Dysfunction; Diabetes Mellitus, Type 2; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Carbohydrates; Polysaccharides; Oligosaccharides; Pyrazines; Triazoles; Trisaccharides; Sitagliptin Phosphate; Acarbose
• Other Study ID Numbers: 2022XD020

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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