Effects of Dorzagliatin on 1st Phase Insulin and Beta-cell Glucose Sensitivity in T2D and Monogenic Diabetes

Inclusion criteria

• Individuals aged ≥ 18 years but < 65years
• Male or female
• Body mass index of over 18 kg/m2 and < 30 kg/m2 Additional Inclusion criteria for recent-onset T2D group

• Diagnosis of T2D for at least 3 months and less than 2 years
• On diet control only
• HbA1c>6.5 % and <8% Additional Inclusion criteria for GK MODY-2 group
• Abnormal fasting plasma glucose >5.6 mmol/l and known heterozygous carrier of pathogenic GK mutation

Exclusion criteria

• Subjects who do not agree to participate in this study.
• Country of birth is unknown
• Body weight less than 45kg
• Acute phase of cerebrovascular and cardiovascular diseases (within 6 months of recruitment).
• Subjects with severe renal dysfunction as defined by eGFR <30 ml/min/1.73m2 or patients receiving renal dialysis (such as haemodialysis or continuous ambulatory peritoneal dialysis).
• Severe hepatic dysfunction as defined by AST and/or ALT > 3 times upper limit of normal
• Severe cardiovascular disease, history of stroke, heart failure (NYHA III or IV) or history of myocardial infarction within last 12 months
• History of drug abuse or excessive alcohol intake based on investigator judgment
• Severe hypoglycaemia resulting in seizure/unconsciousness/coma/hospitalization in the last 3 months before screening
• Diagnosis with Type 1 Diabetes Mellitus (T1DM) or any previous episodes of diabetic ketoacidosis.
• Dehydration, diarrhoea or vomiting at the time of recruitment
• Subjects with severe infection, in perioperative period or with serious injury at the time of recruitment
• Subjects with anaemia (Haemoglobin <9.0mg/dL)
• Pregnant or lactating or intending to become pregnant within 30 days after last dose of study drug.
• Participation in a clinical trial within 30 days before enrolment
• Donation or loss of blood (excluding the volume of blood that will be drawn during screening procedures) as follows: >=300 mL of blood within 30 days prior to study drug administration.
• Subjects judged unsuitable for the study based on investigator judgment
• Use of metformin, sulfonylureas, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 [GLP-1] agonists, sodium glucose transporter 2 inhibitors, insulin, thiazolidinediones, acarbose in the 3 months prior to study enrolment will not be permitted.
• Use of strong or moderate CYP3A4 inhibitors or inducers and cannot be discontinued
• Unwilling or unable to follow protocol requirements.