| Eligibility |
Inclusion Criteria:
1. Subjects have diagnosed with type 2 diabetes according to the Guidelines for
prevention and treatment of type 2 diabetes in China (2020 Edition);
2. Aged 18 to 75 years (inclusive), no gender limitation;
3. Body mass index (BMI) = 24.0 kg/m^2 with stable body weight (less than 5%
self-reported change within 3 months);
4. Subjects diagnosed with type 2 diabetes = 3 years, and not on medication or with a
history of regular medication for no more than 1 week within the 3 months prior to
screening (subjects with a history of medication only include those with a history of
single-agent oral medication and a history of short-term intensive insulin therapy (=
2 weeks)); 5.7.5% = HbA1c = 10.0%;
6.Subjects of childbearing potential must use reliable methods of contraception from the
date of signing an informed consent to at least 3 months after the last dose; 7. The
subject fully understand the trial and possible adverse reactions, has the ability to
communicate properly with the investigator and comply with the research protocol;
8.Voluntarily participate in the trial and sign the informed consent form.
Exclusion Criteria:
1. Fasting plasma glucose = 13.9 mmol/L at screening or a history of severe hypoglycemia
(Serious event requiring help from others with changes in consciousness and/or body)
within 6 months prior to screening;
2. Systolic blood pressure = 160 mmHg or diastolic blood pressure =100 mmHg during
screening;
3. Have one or more positive tests in anti-human immunodeficiency virus antibody or
anti-treponema pallidum-specific antibody;
4. Aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) =2.5x upper limit
of normal (ULN), or Total bilirubin (TBiL)=1.5x ULN, or triglyceride > 5.7 mmol/L or
eGFR < 60 mL/(min*1.73 m^2) during the screening period;
5. Subjects with hematological diseases (e.g., aplastic anemia, myelodysplastic syndrome)
or any disease causing hemolysis or erythrocyte instability (e.g., malaria), or
hemoglobin<100 g/L;
6. Hypercortisolism, polycystic ovary syndrome, abnormal thyroid function (those
requiring medication or who have not reached a stable dose of treatment in 3 months
prior to screening), etc. or other diseases that may affect blood glucose metabolism;
7. Have a personal or family history of medullary thyroid carcinoma (MTC) or type 2
multiple endocrine neoplasia, or other genetic diseases that are susceptible to
medullary cancer, or calcitonin = 50 ng/L(pg/mL);
8. Acute complications of diabetes (including diabetic ketoacidosis, hyperosmolar
nonketotic diabetic coma, lactic acidosis) occurred once or more within 3 months or
twice or more within 6 months before screening;
9. Proliferative diabetic retinopathy, foot ulcers/gangrene, and manifestations of
peripheral neuropathy with obvious symptoms (e.g., gastroparesis, urinary retention,
intestinal obstruction, urinary incontinence, and painful peripheral neuropathy);
10. Subjects with degree II or III atrioventricular block in 12-lead ECG (except for
subjects who use the pacemaker), long QT syndrome or prolonged QTc interval (QTcF:
>450 ms for males, >470 ms for females), or signs of clinically significant localised
ischemic heart disease during the screening period; or those with other heart diseases
that are judged by the investigator to be unsuitable for entry into the study;
11. Any of the following cardiovascular and cerebrovascular events within half a year
before screening: unstable angina pectoris requiring hospitalization, myocardial
infarction, coronary artery bypass grafting, percutaneous coronary intervention
(diagnostic angiography is allowed), moderate to severe congestive heart failure (NYHA
grade III or IV), atrial or ventricular arrhythmia requiring hospitalization (such as
atrial fibrillation and ventricular tachycardia), pacemaker or defibrillator
implantation, transient ischemic attack or cerebrovascular accident (e.g. stroke), or
those with coronary artery bypass grafting or revascularization planned during the
study period;
12. Have chronic or acute pancreatitis ( or have a history of recurrent acute
pancreatitis), or serum amylase and/or lipase = 3x ULN (If lipase cannot be detected
in some centers, it is acceptable to judge only based on amylase),or severe
gastrointestinal disease, such as confirmed reflux esophagitis or gallbladder disease,
or any disease impacting gastric emptying (such as gastric bypass surgery, pyloric
stenosis, except for appendectomy) or gastrointestinal diseases that may be aggravated
by GLP-1 analogues; for subjects with a history of gallbladder stones (gallstone
removal or lithotripsy) and/or cholecystectomy, access to the study will be determined
by investigator after assessing the risk if there are no further sequelae;
13. History of severe respiratory tract, blood system, central nervous system diseases
(e.g., epilepsy, etc.), or history of malignant tumor (except for basal cell carcinoma
or carcinoma in situ that has been clinically cured), mental diseases (e.g.,
depression, anxiety, etc.), or history of other diseases that may endanger the safety
of the subjects and are considered unsuitable for this study in the investigator's
opinion;
14. Subjects who have undergone major surgery within 3 months before screening, or have
ongoing severe or acute infection within 4 weeks before screening, or whose white
blood cell count exceeds 10% of the upper limit of normal during the screening period;
15. Use of drugs that can affect glucose metabolism or directly reduce gastrointestinal
motility within the 3 months prior to screening or expected during the course of the
study, including the cumulative use of systemic glucocorticoids (topical, intraocular
and inhaled preparations), immunosuppressants and cytotoxic drugs for more than 7
days; Large doses of thiazide diuretics (hydrochlorothiazide>100 mg/d, chlorothiazide>
2 g/d, indapamide> 5 mg/d, chlorthalidone> 100 mg/d), anticholinergics,
antispasmodics, etc. for more than 7 consecutive days;
16. Have taken prescription or over-the-counter medications for weight loss (e.g.,
orlistat, sibutramine, rimonabant, phenylpropanolamine, or chlorphenimiindole, etc)
within 3 months prior to screening; or have undergone surgery that can cause weight
instability;
17. Drugs that may cause significant weight gain have been used or are being used within 3
months before screening, including tricyclic antidepressants, atypical antipsychotics
and mood stabilizers (e.g., midazolam, amitriptyline, mirtazapine, paroxetine, phenyl
valproic acid and its derivatives and lithium), etc;
18. Have a serious history of drug or food allergy, or may be allergic to the
investigational product according to the judgment of the investigator;
19. Lost more than 400 mL of blood due to blood donation or other reasons within 3 months
before the screening period;
20. Average alcohol intake more than 21 units of alcohol (male)/14 units of alcohol
(female) per week within the 3 months prior to screening;
21. Regular consumption of caffeine more than 600 mg per day within the 3 months prior to
screening;
22. Smoke more than 20 cigarettes per day within 3 months prior to screening;
23. Have skin abnormalities or dermatitis within a radius of 2 cm of the administration
site;
24. Participation in other drug studies within 3 months prior to screening and the last
received test drug less than 3 months prior to screening; or subjects out of the group
due to adverse events in the previous study; or attempted to participate in other drug
trials during the study;
25. Pregnant (blood pregnancy test positive in screening period) or lactating female;
26. Vaccinated within 28 days before screening or planned to be vaccinated during the
study;
27. Not suitable for this study in the investigator's opinion.
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