Effects of SGLT2i on the Cognitive Function in T2DM Patient (ESCDP)

Study Overview
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Brief Summary
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Type 2 diabetes is associated with diabetic cognopathy, the prevalence of Alzheimer's Disease(AD) in T2DM patients is 1.5 to 2.5 times higher than the general population. Cognitive impairment seriously affects the health and quality of life of the elderly. Prevention and treatment measures for cognitive decline in persons with T2DM has not been well studied. Sodium-glucose transporter-2 (SGLT-2) inhibitors, which lower serum glucose by inhibiting SGLT2-mediated glucose reabsorption in renal proximal tubules, could be neuroprotective. It was recently reported that the SGLT-2 inhibitor improved cognitive function and ameliorated oxidative stress via attenuating mitochondrial dysfunction, insulin resistance, inflammation, and apoptosis in mice or HFD-induced obese rats, that means SGLT-2 inhibitor may provide neuroprotection in the diabetic brain. Hence, Invokana (Canagliflozin) might act as a potent dual inhibitor of AChE and SGLT2. Since the development of diabetes is associated with AD, the design of new AChE inhibitors based on antidiabetic drug scaffolds would be particularly beneficial. Moreover, the present computational study reveals that Invokana (Canagliflozin) is expected to form the basis of a future dual therapy against diabetes associated neurological disorders. The overall goal of this study is to explore the effects of SGLT2 inhibitor on the cognitive function in patients with type 2 diabetes mellitus and make further contribution to the improvement of cognitive function.

Official Title
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Effects of Sodium-glucose Co-transporter-2 Inhibitors on the Cognitive Function in Type 2 Diabetic Patient

Conditions
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Diabetes Mellitus, Type 2, Cognitive Functions Confusion

Intervention / Treatment
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* Drug: Dapagliflozin
* Drug: Metformin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Early onset type 2 diabetes within 3 months 7%<HbA1c<10% Exclusion Criteria: Type 2 diabetes with acute diabetic complications. Type1 diabetes. Other diseases affecting cognitive function (congenital dementia, brain trauma, severe heartdysfunction,severekidneydysfunction,severelungdysfunction, epilepsy, severe hypoglycemic coma, cerebrovascular disease, ischemic heart disease, etc.); Alcohol abuse,mental illness and psychoactive substance abuse History of thyroid disease Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs. Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs. History of depression, schizophrenia or dementia. History of cardio-cerebral vascular events, such as congestive heart failure, myocardial infarction or stroke within 3 months. History of parkinson's diseases, head injury,toxicencephacopathy,epilepsy. Hypohepatia (AST or AST is twice higher than the upper limit) or history of hepatitis or cirrhosis, hepatic encephalopathy. Renal insufficiency (serum creatinine 1.5 times higher than the upper limit) or history of dialysis and nephritic syndrome. Acute infections, tumor, severe arrhythmia, mental disorders, alcohol or medicine addiction. Fertile woman without contraceptives. Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs. Allergic to or have contraindication to the intervention drugs.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapagliflozin<br>12 weeks of Dapagliflozin(10mg/day) treatment, randomly | Drug: Dapagliflozin<br>* Near infrared detection of brain function in diabetic patient at baseline and after 12 weeks of Dapagliflozin(10mg/day) treatment<br>|
| Experimental: Metformin<br>12 weeks of Metformin (1500-2000mg/day) treatment, randomly | Drug: Metformin<br>* Near infrared detection of brain function in diabetic patient at baseline and after 12 weeks of Metformin (1500-2000mg/day) treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of cognitive function assessed by cognitive function scale after 12 weeks |  | Baseline,12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes mellitus, Cognitive Functions, Sodium glucose transporter