Effects of Liraglutid, Dapagliflozin and Acarbose on the Cognitive Function, Olfactory Function, and Odor-induced Brain Activation in Overweight/Obese T2DM Patients Controlled Inadequately With Metformin Monotherapy.

NCT03961659 | Unknown

• 1 other identifier: ZZ2019
• Study Type: interventional
• Target: 87
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, open label, parallel, 16-week study to explore and evaluate the therapeutic effects of liraglutid, dapagliflozin and acarbose on the cognitive function, olfactory function, and odor-induced brain activation in overweight/obese patients with type 2 diabetes mellitus(T2DM) inadequately controlled with metformin monotherapy.

Conditions

Type 2 Diabetes Mellitus; Obesity; Cognitive Impairment

Keywords

Functional MRI; Olfactory function; Liraglutid; Dapagliflozin; Acarbose

Outcome Measures

Primary Outcomes (1)

• Change of olfactory brain activation by fMRI

  Compare the change of olfactory brain activation by fMRI from baseline to 16 weeks' follow-up

  from baseline to 16 weeks' follow-up.

Secondary Outcomes (6)

• Change of cognitive function

  from baseline to 16 weeks' follow-up.

• Proportion of patients whose MoCA<26 scores

  at baseline and at 16 weeks' follow-up.

• Change of blood glycaemic control

  from baseline to 16 weeks' follow-up

• Proportion of patients whose HbA1c<7%

  at 16 weeks' follow-up.

• Proportion of patients whose weight loss>3% and >5%

  from baseline to 16 weeks' follow-up.

Study Arms (3)

Liraglutid

ACTIVE COMPARATOR

Liraglutid will be titrated from 0.6mg/day to a final dose 1.8mg/day during the first 2 weeks, if well tolerated. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but liraglutid could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Liraglutid

Dapagliflozin

ACTIVE COMPARATOR

Dapagliflozin will be initiated and maintained at 10mg/day every morning until the completion of the study. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but dapagliflozin could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Dapagliflozin

Acarbose

ACTIVE COMPARATOR

Acarbose will be initiated at 50mg three times daily for the first week, and then titrated to100mg three times daily if appropriate. Meanwhile, All patients will also continue on their existing dose and regimen of metformin throughout the study. Visits at 4-week intervals will be performed to evaluate the safety of drugs. Metformin dose can be reduced in response to hypoglycaemia, but acarbose could not be adjusted. If the plasma glucose still not achieve the target at the maximum dose, the maximum dose will be maintained until the completion of the study.

Drug: Acarbose

Interventions

Liraglutid DRUG

Liraglutid will be titrated from 0.6mg/day to 1.8mg/day during the first 2 weeks, if well tolerated. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Liraglutid

Dapagliflozin DRUG

Dapagliflozin will be initiated and maintained at 10mg/day every morning until the completion of the study. All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Dapagliflozin

Acarbose DRUG

Acarbose will be initiated at 50mg three times daily for the first week, and then titrated to 100mg three times daily if appropriate.All patients will also continue on their existing dose and regimen of metformin throughout the study.

Also known as: metformin

Acarbose

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≧ 40 and ≦75 years old
• T2DM patients controlled with metformin monotherapy with stable, maximum tolerated doses (≧1500mg/d, ≧12 weeks)
• HbA1c\>7% and ≤9%
• Body mass index(BMI) ≥25kg/m2 and with stable weight during previous 3 months
• Right handedness
• Possessed over 6-year education
• Provision of informed consent prior to any study specific procedures
• Mini-Mental State Examination (MMSE) \>24

You may not qualify if:

• Allergies to research drugs
• Treated with glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter 2 inhibitors, insulins, and glycosidase inhibitors in the previous 6 months
• Moderate to severe renal dysfunction defined as estimated glomerular filtration rate(eGFR)\<60ml/min/1.73m2 ( eGFR was estimated by CKD-EPI creatinine equation using an online calculator).
• Hepatic insufficiency
• A history of neurological and psychiatric disorders, nasal pathologies, abnormal thyroid, pancreatitis, repeated urinary tract infection, chronic gastrointestinal dysfunction, any disease that may worsen by intestinal flatulence, alcohol or substance abuse, steroid treatment
• Any acute disease
• Inability to undergo tests or MRI scanning
• Pregnant or lactating women
• Participating in other clinical trials at the same time or within 6 months prior to the start of the trial

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University

Nanjing, Jiangsu, 210008, China

RECRUITING

Related Publications (1)

• Cheng H, Zhang Z, Zhang B, Zhang W, Wang J, Ni W, Miao Y, Liu J, Bi Y. Enhancement of Impaired Olfactory Neural Activation and Cognitive Capacity by Liraglutide, but Not Dapagliflozin or Acarbose, in Patients With Type 2 Diabetes: A 16-Week Randomized Parallel Comparative Study. Diabetes Care. 2022 May 1;45(5):1201-1210. doi: 10.2337/dc21-2064.

  PMID: 35263425 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Obesity; Cognitive Dysfunction

Interventions

Metformin; dapagliflozin; Acarbose

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Trisaccharides; Oligosaccharides; Polysaccharides; Carbohydrates

Central Study Contacts

Da long Zhu, MD, PhD

CONTACT

86-25-83-105302; zhudldr@gmail.com

Yan Bi, MD, PhD

CONTACT

86-25-83-105302; biyan@nju.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician

Study Record Dates

• First Submitted: May 19, 2019
• First Posted: May 23, 2019
• Study Start: May 1, 2019
• Primary Completion: August 1, 2020
• Study Completion: February 1, 2021
• Last Updated: May 23, 2019

Record last verified: 2019-05

Locations

CN (1)