## Protocol Section
### Identification Module
**NCT ID:** NCT06417489

**Brief Title:** Evaluation of Efficacy and Safety of Combination Therapy of Henagliflozin Proline, Retagliptin and Metformin in New Diagnosed Type 2 Diabetes Patients

**Official Title:** Evaluation of Efficacy and Safety of Combination Therapy of Henagliflozin Proline, Retagliptin and Metformin Compared to Sequential Metformin Therapy in Newly Diagnosed Type 2 Diabetes Patients

#### Organization Study ID Info
**ID:** 2024-165-002
#### Organization
**Class:** OTHER
**Full Name:** Peking University First Hospital
### Status Module
#### Completion Date
**Date:** 2026-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-16

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-11

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2026-05-30

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-31

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-16
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-11
**Study First Submit QC Date:** 2024-05-11
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Peking University First Hospital

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** This study evaluated the efficacy and safety of initial combined treatment of Henggliptin, Retagliptin and Metformin by including new type 2 diabetes patients. This study is a multicenter, randomized, open label, positive control study. It is planned to include 160 new type 2 diabetes patients who meet the inclusion criteria of the study. The study is divided into three stages: screening period (V0, -14d-0), treatment period (V1-V8, D1-24w) and safe follow-up period (V9, 28w), with a total of 10 planned visits. This study was divided into an experimental group and a control group. The experimental group received a one-time addition of 10 mg qd of Henggliptin, 100 mg qd of Regagliptin, and 500mg of Metformin. The control group was first treated with metformin. If the blood sugar level did not meet the standard (fasting blood glucose (FPG)\&gt;7mmol/L, postprandial blood glucose (PPG)\&gt;10mmol/L), Henggeliflozin 10 mg qd was sequentially added. If the blood sugar level did not meet the standard after 4 weeks, Regagliptin 100 mg qd was added. During the follow-up period, evaluate blood glucose control, pancreatic islet function, and safety in both groups of patients.

### Conditions Module

**Conditions:**

- Type 2 Diabetes

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 160

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Henagliflozin Proline 10 mg qd+Regagliptin 100 mg qd+Metformin 500mg bid. The dose of metformin from the first to second week is 500mg bid, and the dose from the third to fourth week is 1000mg bid. If the maximum dose of metformin cannot be tolerated, the researcher shall increase the dosage according to the patient's tolerance situation. The minimum dose is 1000mg/day.

**Intervention Names:**

- Drug: Combination therapy

**Label:** Combination therapy

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Metformin, the dose from the first to second week is 500mg bid, and the dose from the third to fourth week is 1000mg bid. If the maximum dose of metformin cannot be tolerated, the researcher shall increase the dosage according to the patient's tolerance situation. The minimum dose is 1000mg/day. After the fourth week of treatment, blood glucose levels were measured. For those whose blood glucose levels did not meet the standard (fasting blood glucose (FPG)\>7mmol/L, postprandial blood glucose (PPG)\>10mmol/L), 10 mg qd of Henagliflozin Proline was sequentially added. If the blood glucose levels did not meet the standard after 4 weeks of treatment (FPG\>7mmol/L, PPG\>10mmol/L), 100 mg qd of Ruigeliflozin was added

**Intervention Names:**

- Drug: Sequential treatment group

**Label:** Sequential treatment group

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Combination therapy

**Description:** Henagliflozin Proline 10 mg qd+Regagliptin 100 mg qd+Metformin 500mg bid. The dose of metformin from the first to second week is 500mg bid, and the dose from the third to fourth week is 1000mg bid. If the maximum dose of metformin cannot be tolerated, the researcher shall increase the dosage according to the patient\&#39;s tolerance situation. The minimum dose is 1000mg/day.

**Name:** Combination therapy

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Sequential treatment group

**Description:** Metformin, the dose from the first to second week is 500mg bid, and the dose from the third to fourth week is 1000mg bid. If the maximum dose of metformin cannot be tolerated, the researcher shall increase the dosage according to the patient\&#39;s tolerance situation. The minimum dose is 1000mg/day. After the fourth week of treatment, blood glucose levels were measured. For those whose blood glucose levels did not meet the standard (fasting blood glucose (FPG)\&gt;7mmol/L, postprandial blood glucose (PPG)\&gt;10mmol/L), 10 mg qd of Henagliflozin Prolinewas sequentially added. If the blood glucose levels did not meet the standard after 4 weeks of treatment (FPG\&gt;7mmol/L, PPG\&gt;10mmol/L), 100 mg qd of Ruigeliflozin was added

**Name:** Sequential treatment group

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Measure:** Proportion of subjects with HbA1c<7% at 12w

**Time Frame:** From enrollment to the end of treatment at 12 weeks

#### Secondary Outcomes

**Measure:** The proportion of subjects with HbA1c<7% at week 24

**Time Frame:** From enrollment to the end of treatment at 24 weeks

**Measure:** The proportion of subjects with HbA1c<6.5% at 12 week

**Time Frame:** From enrollment to the end of treatment at 12 weeks

**Measure:** The proportion of subjects with HbA1c<6.5% at 24 week

**Time Frame:** From enrollment to the end of treatment at 24 weeks

**Measure:** Changes in HbA1c compared to baseline at 12 weeks

**Time Frame:** From enrollment to the end of treatment at 12 weeks

**Measure:** Changes in HbA1c compared to baseline at 24 weeks

**Time Frame:** From enrollment to the end of treatment at 24 weeks

**Measure:** Changes in fingertip blood glucose (seven point blood glucose spectrum) compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in 2hPPG compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in FBG compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in systolic pressure compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in diastolic pressure compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in body weight compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in waist circumference compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in eGFR compared to baseline at 4w, 8w, 12w, and 24w

**Time Frame:** From enrollment to the end of treatment at 4/8/12/24 weeks

**Measure:** Changes in C-peptide levels during the 12 and 24 weeks compared to baseline during abdominal and 2-hour postprandial periods

**Time Frame:** From enrollment to the end of treatment at 12 and 24 weeks

**Measure:** Changes in insulin levels during the 12 and 24 weeks compared to baseline during abdominal and 2-hour postprandial periods

**Time Frame:** From enrollment to the end of treatment at 12 and 24 weeks

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

1. Untreated newly diagnosed T2DM patients;
2. Age ≥ 18 years old;
3. 8.0% ≤ HbA1c\&lt;11.0%;
4. 19 kg/m2 ≤ BMI\&lt;35 kg/m2;
5. eGFR ≥ 60 ml/min1.73m2;
6. Voluntarily participate and sign an informed consent form

Exclusion Criteria:

1. Pregnant and lactating women, as well as women of childbearing age who are unwilling to take reliable contraceptive measures;
2. Individuals who are known to be allergic to Henggliflozin, Regagliptin, or Metformin;
3. Other types of diabetes except type 2 diabetes;
4. Type 2 diabetes with a history of ketoacidosis (DKA) in the last 6 months;
5. NYHA cardiac grade IV patients;
6. Within 30 days prior to the screening visit, admission due to acute coronary syndrome (ST segment elevation myocardial infarction, non ST segment elevation myocardial infarction, or unstable angina), percutaneous coronary intervention, or cardiac surgery; Or plan to undergo percutaneous coronary intervention or cardiac surgery within 3 months.
7. Confirmed respiratory system diseases (such as chronic obstructive pulmonary disease, pulmonary arterial hypertension, etc.);
8. History of acute or chronic pancreatitis;
9. Uncontrolled hypertension, defined as systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg (average of three supine blood pressure measurements) during screening visits;
10. Patients with orthostatic hypotension and/or systolic blood pressure\&lt;90 mmHg at visit 0 or visit 1, or clinically diagnosed as having low blood volume;
11. Diagnosed malignant tumor patients with an expected life expectancy of less than 1 year;
12. Patients with a history of recurrent urinary and reproductive tract infections (judged by clinical doctors);
13. Patients who participate in other clinical trials within 3 months;
14. Alcohol or drug addiction.
15. In addition to the above, the researchers determined that patients who are not suitable to participate in this clinical trial.

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** nan.gu@pkufh.cn

**Name:** Junqing Zhang

**Phone:** 8613611167278

**Role:** CONTACT

### IPD Sharing Statement Module

**IPD Sharing:** UNDECIDED

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000044882

- Term: Glucose Metabolism Disorders

- ID: D000008659

- Term: Metabolic Diseases

- ID: D000004700

- Term: Endocrine System Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC18

- Name: Nutritional and Metabolic Diseases

- Abbrev: BC19

- Name: Gland and Hormone Related Diseases

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M7115

- Name: Diabetes Mellitus

- Relevance: HIGH

- As Found: Diabetes

- ID: M7119

- Name: Diabetes Mellitus, Type 2

- Relevance: HIGH

- As Found: Type 2 Diabetes

- ID: M11639

- Name: Metabolic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M25403

- Name: Glucose Metabolism Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M7862

- Name: Endocrine System Diseases

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000003920

- Term: Diabetes Mellitus

- ID: D000003924

- Term: Diabetes Mellitus, Type 2

### Intervention Browse Module - Browse Branches

- Abbrev: Hypo

- Name: Hypoglycemic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: AA

- Name: Amino Acids

### Intervention Browse Module - Browse Leaves

- ID: M11667

- Name: Metformin

- Relevance: LOW

- As Found: Unknown

- ID: T15

- Name: Proline

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
