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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Liraglutide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • The third hospital affiliated to the Third Military Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Liraglutide; 12 weeks of liraglutide treatment at adjusting dose, up to 1.8mg/day Drug: liraglutide	Drug: Liraglutide; 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.
Placebo Comparator: Placebo; 12 weeks of Placebo treatment at adjusting dose Drug:Placebo	Drug: placebo; Any hypoglycemic drugs except glucagon-like peptide type 1 (GLP-1) analogue.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Third Military Medical University

Publications and helpful links

General Publications

• Li Q, Jia M, Yan Z, Li Q, Sun F, He C, Li Y, Zhou X, Zhang H, Liu X, Bu X, Gao P, He H, Zhao Z, Zhu Z. Activation of Glucagon-Like Peptide-1 Receptor Ameliorates Cognitive Decline in Type 2 Diabetes Mellitus Through a Metabolism-Independent Pathway. J Am Heart Assoc. 2021 Jul 20;10(14):e020734. doi: 10.1161/JAHA.120.020734. Epub 2021 Jul 10.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2018
• Primary Completion (Actual): February 1, 2019
• Study Completion (Actual): May 1, 2019

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): July 10, 2019
• Last Update Submitted That Met QC Criteria: July 9, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Liraglutide; Type 2 diabetes mellitus; Cognitive function
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: Liraglutide

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