Cofrogliptin every two weeks added to metformin and dapagliflozin versus daily linagliptin for 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 trial will test whether adding cofrogliptin every two weeks to metformin and dapagliflozin lowers HbA1c better than adding daily linagliptin in adults with type 2 diabetes whose blood sugar is not controlled on metformin plus an SGLT2 inhibitor.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 170 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Huazhong University of Science and Technology (Academic / other)
• Locations: 2 sites (Wuhan, Hubei and 1 other locations)
• Trial ID: NCT07019012 on ClinicalTrials.gov

What this trial studies

This phase 4 interventional comparison assigns adults with type 2 diabetes who remain above target HbA1c on stable metformin and dapagliflozin to receive either cofrogliptin every two weeks or daily linagliptin in addition to their existing therapy. The primary outcome is the change in glycated hemoglobin (HbA1c) from baseline to 24 weeks. Participants will be followed for safety and changes in fasting plasma glucose and other metabolic measures, with visits at Wuhan University-affiliated hospitals. Eligible participants must have been on dapagliflozin 10 mg and stable metformin for at least 12 weeks and meet specified HbA1c, BMI, and kidney function limits.

Who should consider this trial

Good fit: Adults (≥18 years) with type 2 diabetes who have been on dapagliflozin 10 mg daily and a stable dose of metformin for ≥12 weeks, with HbA1c between 7.0% and 10.0%, eGFR ≥60 ml/min/1.73 m2, BMI ≤40 kg/m2, and willingness to perform home glucose monitoring are the ideal candidates.

Not a fit: People with type 1 diabetes, those with HbA1c outside the 7.0–10.0% range, significant renal impairment (eGFR <60), or who are not already on metformin plus an SGLT2 inhibitor are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, adding cofrogliptin every two weeks could improve or match HbA1c control while offering less frequent dosing compared with a daily DPP-4 inhibitor.

How similar studies have performed: Daily DPP-4 inhibitors like linagliptin have established efficacy for lowering HbA1c, but cofrogliptin given every two weeks is a newer dosing approach with limited published evidence to date.

Eligibility criteria

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.

Where this trial is running

Wuhan, Hubei and 1 other locations

• Wuhan University People's Hospital — Wuhan, Hubei, China (Recruiting)
• Wuhan University People's Hospital — Wuhan, Hubei, China (Recruiting)

Study contacts

• Principal investigator: XueFeng Yu, Doctor — Tongji Hosptial Affiliated to Tongji Medical College of Huazhong University fo Science and Technology
• Study coordinator: ZheLong Liu, Doctor

Conditions T2DM