Effects of Sodium-glucose Co-transporter-2 Inhibitors on the Cognitive Function in Type 2 Diabetic Patient
Overview
- Phase
- Phase 3
- Intervention
- Canagliflozin
- Conditions
- Diabetes Mellitus, Type 2
- Sponsor
- Third Military Medical University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Changes of cognitive function assessed by cognitive function scale
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Zhiming Zhu
Director of the Department of Hypertension & Endocrinology, Daping Hospital
Third Military Medical University
Eligibility Criteria
Inclusion Criteria
- •Newly onset type 2 diabetes within 3 months
- •7%\<HbA1c\<10%
Exclusion Criteria
- •Type 2 diabetes with acute diabetic complications.
- •Type1 diabetes.
- •Thyroid dysfuncition.
- •Any surgical or medical conditions that significantly influence absorption, distribution, metabolism or excretion of the intervention drugs.
- •History of cardio-cerebral vascular events, such as congestive heart failure, myocardial infarction or stroke within 3 months.
- •Hepatic insufficiency (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.
- •Alcohol or medicine addiction, psychoactive substance abuse.
- •Other diseases affecting cognitive function (congenital dementia, brain trauma, parkinson's diseases, toxicencephacopathy,epilepsy, mental disorders, severe lungdy sfunction, epilepsy, severe hypoglycemic coma, cerebrovascular disease, ischemic heart disease, etc.)
Arms & Interventions
Canagliflozin
12 weeks of Canagliflozin(100mg/day) treatment, randomly
Intervention: Canagliflozin
Sitagliptin
12 weeks of Sitagliptin (100mg/day) treatment, randomly
Intervention: Sitagliptin
Outcomes
Primary Outcomes
Changes of cognitive function assessed by cognitive function scale
Time Frame: 12 weeks
cognitive function scale
Secondary Outcomes
- Changes of standardized uptake values of brain and splanchnic organs assessed by 18F-PET-CT(1 week)
- Changes of brain function assessed by near infrared brain functional imaging(4 week)
- Changes of urinary sodium and glucose excretion (mmol/24h)(1 week)