Clinical trial NCT05553093: Effects of Tirzepatide and Insulin Glargine on Glucolipid Metabolism and Brain Function in Patients With Type 2 Diabetes
Official title: Nanjing First Hospital, Nanjing Medical University
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Nanjing First Hospital, Nanjing Medical University
Sponsor class: OTHER
First posted: 2022-09-23
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The effects of Tirzepatide and Insulin Glargine on glucose and lipid metabolism and inflammation in patients with type 2 diabetes mellitus. Effects of Tirzepatide on the occurrence and development of cognitive impairment in diabetic patients and its associated pattern of changes in brain neural network characteristics.

Detailed description: The aim of the study is to investigate the effects of Tirzepatide and Insulin Glargine on glucose and lipid metabolism and inflammation in patients with type 2 diabetes mellitus. Meanwhile, this study will evaluate the effects of Tirzepatide on the development of cognitive impairment and its associated pattern of changes in neural network characteristics in diabetic patients.

Eligibility criteria: Inclusion Criteria:

* Type 2 diabetes was diagnosed according to World Health Organization(WHO) classification or other locally applicable diagnostic criteria.
* Received stable metformin with or without sulfonylureas at least 2 months prior to visit 1 and between visits 1 and 3 (metformin ≥ 1000 mg/ day and does not exceed the maximum dose specified in the nationally approved guidelines;Sulfonylureas should be at least half of the maximum dose as stated in the national approved instructions).
* No insulin treatment (except for gestational diabetes or short-term use in acute Settings \[duration ≤14 days\]).
* At visit 1, HbA1c ≥ 7.5% and ≤ 11.0% was determined according to the central laboratory.
* Body mass index (BMI) ≥ 23 kg/m2.

Exclusion Criteria:

* Type 1 Diabetes Mellitus (T1DM)
* Had chronic or acute pancreatitis at any time prior to visit 1.
* A history of proliferative diabetic retinopathy or diabetic macular degeneration or non-proliferative diabetic retinopathy requiring acute treatment.
* History of severe hypoglycemia and/or insensitive hypoglycemia within 6 months prior to visit 1.
* History of ketoacidosis or hyperosmolar state/coma
* Have a known clinically significant gastric emptying disorder (e.g., severe diabetic gastroparesis or gastric outlet obstruction), have received or plan to undergo gastric bypass surgery or restrictive bariatric surgery (e.g., Lap-Band®) during the study period, or take long-term medications that directly affect gastrointestinal motility.
* Had any of the following cardiovascular diseases in the 2 months prior to the visit: acute myocardial infarction or cerebrovascular accident (stroke) or hospitalization due to congestive heart failure (CHF).
* New York Heart Association Classification of Heart Function Class III and Class IV CHF.
* Have acute or chronic hepatitis, have signs or symptoms of any liver disease other than non-alcoholic fatty liver disease (NAFLD), or have alanine aminotransferase (ALT) levels \> 3.0 times the upper limit of the normal range determined by the central laboratory at visit 1;For NAFLD patients, only ALT levels ≤ 3.0 times the upper limit of the normal range (ULN) were eligible for this trial.
* The estimated glomerular filtration rate (eGFR) calculated based on the Chronic Kidney Disease Epidemiology Collaboration equation（CKD-EPI）formula was less than 45 mL/min/1.73 m2, as determined by the central laboratory at visit 1.
* The researchers suggest that there is evidence of significant, poorly controlled endocrine abnormalities, such as thyrotoxicosis or adrenal crisis.
* Family or personal history of medullary thyroid cancer (MTC) or type 2 multiple endocrine tumor syndrome.
* Serum calcitonin level ≥ 35 ng/L (pg/mL) was determined by the central laboratory at visit 1.
* There was significant evidence of active autoimmune abnormalities (e.g., lupus or rheumatoid arthritis) and the investigators suggested that systemic glucocorticoid therapy might be required in the following 12 months.
* Has received an organ transplant (corneal transplant allowed) or is waiting for an organ transplant.
* A history of active or untreated malignancy, or a remission period of less than 5 years for a clinically significant malignancy (other than basal or squamous cell skin cancer, carcinoma in situ of the cervix, or carcinoma in situ of the prostate).
* Presence of any other medical history (e.g., known drug or alcohol abuse or mental illness) that the investigator considered would have prevented the patient from complying with and completing the study protocol.
* Presence of any blood disorders that may interfere with HbA1c measurements (e.g., hemolytic anemia, sickle cell disease).

Primary outcomes:
measure: blood sugar changes
timeFrame: 40 weeks
measure: blood lipid changes
timeFrame: 40 weeks
measure: Brain function
timeFrame: 40 weeks
Secondary outcomes:
measure: Body composition analysis
timeFrame: 40 weeks
measure: Inflammation factors, including adiponectin,leptin,IL-1,IL-6,IL-18,TNF-α,ghrelin,asprosin.
timeFrame: 40 weeks
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Nanjing First Hospital
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital with Nanjing Medical University
name: Jianhua Ma, Doctor
role: STUDY_DIRECTOR
References: