NCT07441187

Efficacy and Safety of Henagliflozin, Retagliptin, and Metformin Extended-Release Tablets in Chinese Patients With Type 2 Diabetes Mellitus

• Status: Not Yet Recruiting
• Phase: —
• Study type: Observational
• Enrollment: 300 (estimated)
• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

Summary

Given the significant and growing burden of Type 2 Diabetes (T2DM) in China, there is a continuous need for effective, convenient, and well-tolerated treatment strategies. This Phase IV, multicenter, prospective, observational study aims to evaluate the real-world effectiveness and safety of a novel, once-daily, fixed-dose combination (FDC) tablet containing Henagliflozin (SGLT2 inhibitor), Retagliptin (DPP-4 inhibitor), and Metformin Extended-Release in Chinese patients with T2DM. The study plans to enroll approximately 300 patients across 30 sites, stratified into two cohorts: newly diagnosed, drug-naïve patients and those with inadequate glycemic control on a single prior oral antidiabetic drug. The primary objective is to assess the change in Glycated Hemoglobin (HbA1c) from baseline after 24 weeks of treatment. Key secondary objectives include evaluating the proportion of patients achieving HbA1c targets (\<7.0% and ≤6.5%), assessing changes in other metabolic parameters such as body weight, blood pressure, fasting and postprandial glucose, and lipid profiles, and monitoring treatment adherence. The safety evaluation will comprehensively document all adverse events, with special attention to events of interest including hypoglycemia, urinary/genital infections, volume-related events, and diabetic ketoacidosis. The study design includes a screening period, a 2-week run-in with lifestyle intervention, a 24-week core treatment period where eligible patients receive the FDC therapy, and a final safety follow-up. Efficacy and safety assessments are scheduled at baseline, Week 4, Week 12, and Week 24. Statistical analysis will be primarily descriptive, focusing on changes from baseline for continuous endpoints and frequency distributions for categorical endpoints, with analyses conducted separately for the two patient cohorts. The study will be conducted in full compliance with Good Clinical Practice (GCP), the Declaration of Helsinki, and relevant Chinese regulations, requiring prior ethics committee approval and written informed consent from all participants. This real-world evidence study seeks to confirm the clinical benefits and safety profile of this triple-combination therapy observed in earlier controlled trials, providing practical insights into its use in routine management of T2DM within the Chinese healthcare context.

Detailed description

1. Rationale China faces a high and growing burden of Type 2 Diabetes (T2DM). This Phase IV study evaluates a novel, once-daily, oral triple-combination therapy in a real-world setting. The fixed-dose combination (FDC) contains Henagliflozin (SGLT2 inhibitor), Retagliptin (DPP-4 inhibitor), and Metformin XR. These agents have complementary mechanisms: SGLT2 inhibition increases urinary glucose excretion, DPP-4 inhibition enhances incretin effects, and metformin reduces hepatic glucose output and improves insulin sensitivity. Prior Phase III data showed superior glycemic efficacy of this triple combination versus dual therapy. This study aims to confirm its effectiveness and safety in routine clinical practice. 2. Objectives \& Endpoints Primary Objective: To evaluate the change in HbA1c from baseline after 24 weeks of FDC treatment. Secondary Objectives: To assess the proportion of patients achieving HbA1c targets (\<7.0%, ≤6.5%), glycemic control without hypoglycemia, adherence, and changes in other metabolic parameters (weight, blood pressure, lipids, glucose). Safety Objective: To evaluate the FDC's safety profile. Primary Endpoint: Change in HbA1c from baseline to Week 24. Key Secondary Endpoints: Proportions achieving HbA1c targets; changes in body weight, systolic/diastolic blood pressure, fasting/postprandial glucose, lipid profiles; adherence rate; hypoglycemic events. Safety Endpoints: Incidence of Adverse Events (AEs), Serious AEs (SAEs), and AEs of Special Interest (e.g., hypoglycemia, urinary/genital infections, volume depletion, diabetic ketoacidosis, acute kidney injury). 3. Study Design This is a multicenter, prospective, observational, dual-cohort study targeting 300 patients from \~30 sites. Cohort 1 (n≈100): Newly diagnosed, drug-naïve T2DM (HbA1c 8.0-11.0%). Cohort 2 (n≈200): Patients with inadequate control (HbA1c 7.0-11.0%) on one prior oral antidiabetic drug (OAD). Study Flow: Screening/Run-in (Up to 5 weeks): Eligibility confirmed. A 2-week run-in involves lifestyle intervention (all) + continuation of prior OAD (Cohort 2 only). Treatment (24 weeks): Eligible patients start FDC tablet (one tablet QD). Assessments at Weeks 4, 12, and 24. Safety Follow-up: Telephone follow-up 7 days after last dose. 4. Key Eligibility Inclusion: Age 18-70; T2DM diagnosis; meets Cohort 1 or 2 criteria; BMI \>19 \& ≤40 kg/m². Exclusion: Type 1 diabetes; significant cardiovascular/renal/hepatic disease; history of pancreatitis, recurrent UTIs/ genital infections; pregnancy. 5. Assessments Efficacy: HbA1c, fasting plasma glucose, 2h postprandial glucose (meal tolerance test), insulin/C-peptide, body weight, waist circumference, blood pressure, lipid profile, uric acid. Safety: Physical exams, vital signs, lab tests (hematology, biochemistry, renal/hepatic function, urinalysis), and continuous AE monitoring. 6. Statistical Plan Analysis Populations: Full Analysis Set (FAS): Primary efficacy population. Safety Set (SS): All patients receiving ≥1 dose. Analysis: Descriptive statistics. Changes from baseline presented as mean ± SD with 95% CI. Analyses performed separately for both cohorts. One interim analysis is planned. 7. Ethics \& Compliance The study will be conducted per ICH-GCP, Declaration of Helsinki, and Chinese regulations. IRB/EC approval and written informed consent are mandatory prior to initiation. Participant confidentiality is protected. 8. Planned Timeline Site Activation \& Enrollment: Nov 2025 - Jun 2026 Treatment \& Follow-up: Through Dec 2026 Data Analysis \& Reporting: 2027

Conditions

• T2DM (Type 2 Diabetes Mellitus)

Interventions

Type	Name	Description
DRUG	Henagliflozin, Retagliptin, and Metformin Extended-Release Tablets	After the run-in period, eligible patients who meet the criteria for receiving the investigational drug will discontinue their prior antidiabetic therapy. Based on the investigator's clinical judgment of the patient's condition, the investigational drug Henagliflozin/Retagliptin/Metformin Extended-Release Tablet (containing Henagliflozin 10 mg, Retagliptin Phosphate 100 mg, and Metformin Hydrochloride 1000 mg per tablet) will be prescribed. The dosage is one tablet once daily in the morning, taken with or without food. It is recommended to take the medication at approximately the same time each day. The tablet should be swallowed whole and must not be chewed.

Timeline

• Start date: 2026-02-20
• Primary completion: 2027-12-31
• Completion: 2027-12-31
• First posted: 2026-02-27
• Last updated: 2026-02-27