Clinical trial NCT03961659: 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.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Type 2 Diabetes Mellitus
Obesity
Cognitive Impairment
Keywords: Functional MRI
Olfactory function
Liraglutid
Dapagliflozin
Acarbose
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2019-05-23
Enrollment: 87
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change of olfactory brain activation by fMRI
timeFrame: from baseline to 16 weeks' follow-up.
Secondary outcomes:
measure: Change of cognitive function
timeFrame: from baseline to 16 weeks' follow-up.
measure: Proportion of patients whose MoCA<26 scores
timeFrame: at baseline and at 16 weeks' follow-up.
measure: Change of blood glycaemic control
timeFrame: from baseline to 16 weeks' follow-up
measure: Proportion of patients whose HbA1c<7%
timeFrame: at 16 weeks' follow-up.
measure: Proportion of patients whose weight loss>3% and >5%
timeFrame: from baseline to 16 weeks' follow-up.
measure: Olfactory threshold test
timeFrame: from baseline to 16 weeks' follow-up.
Other outcomes:
Locations:
city: Nanjing
country: China
facility: at Division of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University
state: Jiangsu
Study officials:
References:
citation: 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.