Cofrogliptin Once Every 2 Weeks as Add-on Therapy to Metformin and Dapagliflozin Versus Daily Linagliptin in Patients With Type 2 Diabetes.

Cofrogliptin Once Every 2 Weeks as Add-on Therapy to Metformin and Dapagliflozin Versus Daily Linagliptin in Patients With Type 2 Diabetes: A Multicenter, Randomized, Open-Label, Active-Controlled, Non-inferiority Trial

This study is designed to evaluate the change in glycated hemoglobin (HbA1c) levels from baseline to 24 weeks after the combination therapy of cofrogliptin, metformin and SGLT2i (dapagliflozin) in type 2 diabetes mellitus (T2DM) patients with poor control of glucose level by metformin and SGLT2i combination therapy.

The primary objective of this study is to evaluate the change in glycated hemoglobin (HbA1c) levels from baseline to 24 weeks after the combination therapy of cofrogliptin, metformin and SGLT2i (dapagliflozin) in type 2 diabetes mellitus (T2DM) patients with poor control of glucose level by metformin and SGLT2i combination therapy, as well as the comparison of efficacy of cofrogliptin and linagliptin. Patients will be assigned to receive the treatment of SGLT2i+metformin+cofrogliptn or SGLT2i+metformin+linagliptin.

Inclusion Criteria:

• Able to understand and voluntarily sign a written informed consent form.
• Male or female subjects aged 18 years and above .
• Meet the diagnostic criteria for Type 2 Diabetes Mellitus (T2DM).
• Have been on initial SGLT2i monotherapy (dapagliflozin) at a dose of 10 mg daily for at least 12 weeks.
• Have received metformin treatment for ≥12 weeks, with a stable dose maintained during the screening period (≥1500 mg/day if tolerable or at the maximum tolerated dose (<1500 mg/day but ≥1000 mg/day), and no dosage adjustment).
• HbA1c levels within the range: 7.0% < HbA1c ≤ 10.0%.
• Fasting plasma glucose (FPG) < 15 mmol/L.
• Body Mass Index (BMI) ≤ 40 kg/m2.
• Estimated Glomerular Filtration Rate (eGFR) ≥ 60 ml/min/1.73m2.
• Agree to maintain the same diet and exercise habits throughout the trial period, willing and able to accurately use a home blood glucose meter for self-monitoring of blood glucose (SMBG) and keep records.

Exclusion Criteria:

• Type 1 Diabetes Mellitus.
• Any type of secondary diabetes.
• Pending or having undergone pancreatic or β-cell transplantation.
• History of pancreatitis or pancreatic resection.
• Complicated with diabetic ketoacidosis or hyperosmolar coma.
• Moderate or severe hepatic insufficiency of any cause. Hepatic insufficiency is defined as screening period levels of ALT (SGPT), AST (SGOT), or alkaline phosphatase serum levels exceeding 3 times the upper limit of normal (ULN).
• Acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina), stroke, or transient ischemic attack (TIA) within the last 3 months.
• Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 100 mmHg.
• Hemoglobin levels < 10 g/l or 100 mg/dl.
• More than 2 recurrent genitourinary infections within the last 3 months.
• History of bariatric surgery or other gastrointestinal surgeries leading to chronic malabsorption within the last 2 years.
• Weight instability due to anti-obesity medication within the last 3 months or any other treatment (such as surgery, aggressive diet plans) at screening.
• History of cancer (excluding basal cell carcinoma) and/or cancer treatment within the last 5 years.
• Human Immunodeficiency Virus (HIV) infection.
• Severe peripheral vascular disease.
• Hematological malignancy or any disorder causing hemolysis or erythrocyte instability (e.g., malaria, babesiosis, hemolytic anemia).
• Concurrent immune system diseases or currently receiving systemic corticosteroid therapy.
• Changes in thyroid hormone dosage within the last 6 weeks, or any other uncontrolled endocrine or metabolic disorder outside of T2DM.
• Alcohol or drug abuse within the last 3 months that may reduce trial compliance, or any chronic condition deemed by the investigator as likely to reduce study compliance or medication adherence.
• Known allergy to the trial medication components or other chemically similar drugs or excipients.
• Pregnant women, women planning pregnancy during the study or breastfeeding, subjects unwilling to use reliable contraception (including condoms, spermicides, or intrauterine devices) from signing the informed consent form until 28 days after the last dose of trial medication, or women planning to use progesterone-containing contraceptives during this period. Men with plans for conception during the study.
• Participation in any other clinical study within the last 30 days.