Efficacy and Safety Comparison of Cofrogliptin Add-on Versus Metformin Dose-escalation in Type 2 Diabetes Patients Inadequately Controlled With SGLT-2 Inhibitors Plus Low-Dose Metformin:A Multicenter, Open-Label Trial

NCT06863532 | Recruiting DMC

• 1 other identifier: 2024-0986
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to evaluate the change in glycated hemoglobin (HbA1c) levels of adding cofrogliptin compared to escalation of metformin dose after 24 weeks in type 2 diabetes patients who have failed to achieve adequate glycemic control despite receiving combination therapy with SGLT2i and metformin. Participants will be asked to use either cofrogliptin combined with SGLT2i and metformin or SGLT2i combined with increased dose of metformin.

Conditions

Type 2 Diabetes

Keywords

t2dm

Outcome Measures

Primary Outcomes (1)

• the change in glycated hemoglobin (HbA1c) levels

  the change in glycated hemoglobin (HbA1c) levels of adding cofrogliptin compared to escalation of metformin dose after 24 weeks in type 2 diabetes patients who have failed to achieve adequate glycemic control despite receiving combination therap

  throughout the study, about 1 year

Secondary Outcomes (6)

• The proportion of subjects with HbA1c < 7.0% and < 6.5%

  throughout the study, about 1 year

• 2h-PPG and FPG

  throughout the study, about 1 year

• Change in HbA1c levels

  throughout the study, about 1 year

• Changes in body weight, fasting C-peptide, insulin sensitivity, and β-cell function

  throughout the study, about 1 year

• proportion of subjects who withdrew

  throughout the study, about 1 year

Study Arms (2)

cofrogliptin add-on group

EXPERIMENTAL

The cofrogliptin add-on group will continue their existing SGLT2i plus metformin regimen and dosing, with the add-on of cofrogliptin over 24 weeks of triple combined therapy.

Drug: Metformin dose escalation

Metformin dose escalation group

ACTIVE COMPARATOR

The metformin dose escalation group will have their metformin dose gradually increased to the target dose

Drug: Cofrogliptin+SGLT2i+Metformin

Interventions

Cofrogliptin+SGLT2i+Metformin DRUG

The cofrogliptin add-on group will continue their existing SGLT2i plus metformin regimen and dosing, with the add-on of cofrogliptin over 24 weeks of triple combined therapy.

Metformin dose escalation group

Metformin dose escalation DRUG

The metformin dose escalation group will have their metformin dose gradually increased to the target dose.

cofrogliptin add-on group

Eligibility Criteria

• Age: 18 Years - 74 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign a written informed consent form.
• Male or female aged 18-74 years (inclusive).
• Meet the diagnostic criteria for type 2 diabetes mellitus (T2DM).
• Have initiated treatment with any one of the SGLT2i monotherapy (dapagliflozin 10mg/d, canagliflozin 100mg/d, empagliflozin 10mg/d, ertugliflozin 5mg/day, or henagliflozin 10mg/day) for at least 8 weeks.
• Have received 500-1000mg/day metformin treatment for at least 8 weeks with a stable, unchanged dose maintained during the screening period.
• HbA1c level within the range of 7.5% to 9.5% inclusive.
• Fasting blood glucose (FBG) level less than 15 mmol/L before randomization.
• Body mass index (BMI) less than or equal to 40 kg/m2 before randomization.
• Urine ketone test negative before randomization.
• Estimated glomerular filtration rate (eGFR) of 60 ml/min/1.73m2 or higher before randomization.
• Agree to maintain the same diet and exercise habits throughout the trial, and be willing and able to correctly use a home blood glucose meter for self-monitoring of blood glucose (SMBG) and keep records.

You may not qualify if:

• Type 1 diabetes mellitus.
• Various types 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 liver insufficiency of any cause, defined as ALT (SGPT), AST (SGOT), or alkaline phosphatase serum levels greater than 3 times the upper limit of normal (ULN) during the screening period.
• Acute coronary syndrome (ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina), stroke, or transient ischemic attack (TIA) within the past 3 months.
• Uncontrolled hypertension: systolic blood pressure ≥ 160 mmHg or diastolic blood pressure ≥ 90 mmHg.
• Hemoglobin level less than 10 g/l or 100 mg/dl.
• Recurrent genitourinary infections more than twice within the past 3 months.
• History of bariatric surgery or other gastrointestinal surgeries causing chronic malabsorption within the past 2 years.
• Received anti-obesity medication within the past 3 months or any other treatment (e.g., surgery, radical diet plans) that led to unstable body weight at the time of screening.
• History of cancer (except basal cell carcinoma) and/or cancer treatment within the past 5 years.
• Human immunodeficiency virus (HIV) positivity.
• Severe peripheral vascular disease.

Sponsors & Collaborators

• Second Affiliated Hospital, School of Medicine, Zhejiang University: lead
• Ningbo Medical Center Lihuili Hospital: collaborator
• Hangzhou Traditional Chinese Medicine Hospital: collaborator
• Wenzhou Central Hospital: collaborator
• The Second Affiliated Hospital of Dalian Medical University: collaborator

Study Sites (1)

Second Affiliated Hospital, School of Medicine, Zhejiang University

Hangzhou, Zhejiang, China

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Chao Zheng, Doctor

  Second Affiliated Hospital, School of Medicine, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wenheng Zeng, Doctor

CONTACT

+86 137 5711 8319; 42590910@qq.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 7, 2025
• Study Start: March 30, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: March 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)