Effects of Liraglutide on the Cognitive Function in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Type 2 diabetes mellitus (T2DM) can impaire cognitive function,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. Glucagon-like peptide-1 (GLP-1) is a member of an endogenous class of incretin hormones synthesized in intestinal epithelial L-cells.GLP-1 enhances glucose-dependent secretion of insulin,inhibits glucagon secretion, slows gastric emptying and reduces food intake. Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue. It has been proved that Liraglutide can improve insulin resistance and cognitive function in AD animals. Therefore, it is speculated that Liraglutide may interfere with the occurrence and development of cognitive dysfunction in patients with T2DM. In order to confirm the effects, the investigators conduct an open, prospective, positive controlled study in patients with T2DM. The effect on BMI,waist circumference, hip circumference, waist-to-hip ratio,fasting plasma glucose，glycosylated hemoglobin,blood lipids and cognitive function were measured to explore the effects of liraglutide in patients with T2DM. The overall goal of this study is to explore the effects of liraglutide 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 Liraglutide on the Cognitive Function in Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes。 Exclusion Criteria: Type 2 diabetes with acute diabetic complications. Type 1 diabetes. Other diseases affecting cognitive function (congenital dementia,brain trauma,severe heart dysfunction,severe kidney dysfunction,severe lung dysfunction,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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Liraglutide<br>12 weeks of liraglutide treatment at adjusting dose, up to 1.8mg/day Drug: liraglutide | Drug: Liraglutide<br>* Liraglutide is a glucagon-like peptide type 1 (GLP-1) analogue. It has been proved that Liraglutide can improve insulin resistance and cognitive function in AD animals. Therefore, it is speculated that Liraglutide may interfere with the occurrence and development of cognitive dysfunction in patients with T2DM. In order to confirm the effects, the investigators conduct an open, prospective, positive controlled study in patients with T2DM.<br>|
| Placebo Comparator: Placebo<br>12 weeks of Placebo treatment at adjusting dose Drug:Placebo | Drug: placebo<br>* Any hypoglycemic drugs except glucagon-like peptide type 1 (GLP-1) analogue.<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. | The cognitive function will be calculated from performance on the following measures: (1)Digit Span Test(DST);(2) Rey Auditory Verbal Learning(RAVL);(3) Long-Delay Free Recall(LDFR);(4) Trail Making Test(TMT);(5) Animal Naming Test(ANT);(6) Clock Drawing Test(CDT);(7)Minimum Mental State Examination(MMSE);(8)Memory and executive screening(MES);(8)functional near-infrared spectroscopy. | Baseline,4weeks,8weeks，12weeks(End of Trial) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of systolic blood pressure and diastolic blood pressure | Change of systolic blood pressure and diastolic blood pressure compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of fasting plasma glucose | Change of fasting plasma glucose compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of HbA1c | Change of HbA1c compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of lipid profile | Change of lipids profiles (TC, HDL-C, LDL-C, TG) in mmol/L compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of liver enzymes | Change of liver enzymes (ALT, AST in IU/L) compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of kidney function | Change of kidney function（serum creatinine in umol/L、eGFR in ml/min） compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of CRP | Change of CRP compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of Body mass index(BMI) | Change of Body mass index(BMI) compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of waist circumference | Change of waist circumference compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of hip circumference | Change of hip circumference compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 
| Change of waist-to-hip ratio | Change of waist-to-hip ratio compared with baseline, and between the intervention and control group at the end of the study (12 weeks) | Baseline,4weeks,8weeks，12weeks(End of Trial) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, Cognitive function, Liraglutide