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.

NCT ID: NCT03961659

Last Updated: 2019-05-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-31
• Study Completion Date: 2021-02-28

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.

Detailed Description

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 T2DM inadequately controlled with metformin monotherapy.We have 1 principle investigator, 6 sub-investigators and 1 nurse in research centre. The sub-investigators will screen in the outpatient and inpatient departments to enroll 87 patients (29 for each arm) totally with the inclusion and exclusion criteria in 12 months. The patients will be randomized at a 1:1:1 ratio into liraglutid, dapagliflozin and acarbose treatment group with a computer-generated random order. All patients will also continue on their existing dose and regimen of metformin throughout the study. At the baseline, clinical information collection, 100g-steamed bread meal test, biochemical measurement, body composition analysis, cognitive assessment, olfactory test and functional magnetic resonance imaging(fMRI) scan will be conducted for all patients. During the treatment period, visits at 4-week intervals will be performed to evaluate the safety of drugs and adjust the dose of metformin if hypoglycaemia occurs; meanwhile, fasting and 2-hour postprandial plasma glucose assayed by fingerstick, physical examination, and olfactory test will be conducted. At the end of the study, all of the assessments will be performed again for all recruited subjects, including early withdrawal patients.

Conditions

Type 2 Diabetes Mellitus; Obesity; Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Liraglutid

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.

Group Type: ACTIVE_COMPARATOR

Liraglutid

Intervention Type: 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.

Dapagliflozin

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.

Group Type: ACTIVE_COMPARATOR

Dapagliflozin

Intervention Type: 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.

Acarbose

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.

Group Type: ACTIVE_COMPARATOR

Acarbose

Intervention Type: 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.

Interventions

Liraglutid

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.

Intervention Type: DRUG

Dapagliflozin

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.

Intervention Type: DRUG

Acarbose

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.

Intervention Type: DRUG

Other Intervention Names

metformin; metformin; metformin

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

OTHER

Sponsor Role: lead

Responsible Party

Dalong Zhu

Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

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

Nanjing, Jiangsu, China

Site Status: RECRUITING

Countries

China

Central Contacts

Da long Zhu, MD, PhD

Role: CONTACT

zhudldr@gmail.com

86-25-83-105302

Yan Bi, MD, PhD

Role: CONTACT

biyan@nju.edu.cn

86-25-83-105302

Facility Contacts

Dalong Zhu, MD,PhD

Role: primary

zhudldr@gmail.com

86-25-83-105302

Yan Bi, MD,PhD

Role: backup

biyan@nju.edu.cn

86-25-83-105302

References

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.

Reference Type: DERIVED

PMID: 35263425 (View on PubMed)

Other Identifiers

ZZ2019

Identifier Type: -

Identifier Source: org_study_id