Henagliflozin on Liver Fibrosis in Patients with MASLD and T2DM

NCT06762223 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: 2024NL-195-01
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 1

Brief Summary

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing due to changes in economic conditions and lifestyle, and it is anticipated to become a significant liver disease burden in the future. This is particularly true for patients with MASLD who also have type 2 diabetes mellitus (T2DM), as the rate of comorbidity between these conditions has risen in recent years due to their shared mechanisms, necessitating careful management of both. Liver fibrosis is a critical concern, as poor blood glucose control can worsen liver fibrosis, which in turn complicates blood sugar management. Therefore, addressing liver fibrosis in patients with MASLD and T2DM is urgent, yet there are currently no targeted therapies to reverse its progression. SGLT2 inhibitors, have shown promise in potentially reversing liver fibrosis, but existing research is limited and has not adequately focused on liver fibrosis improvement, highlighting the need for more robust evidence-based studies.

Conditions

Metabolic Dysfunction-associated Steatotic Liver Disease; Type 2 Diabetes Mellitus

Keywords

metabolic dysfunction-associated steatotic liver disease; type 2 diabetes mellitus; Henagliflozin; SGLT2i; Liver fibrosis

Outcome Measures

Primary Outcomes (1)

• Liver stiffness measurements (LSM) of subjects

  As determined by magnetic resonance elastography (MRE)

  From enrollment to the treatment at 24 and 48 weeks

Secondary Outcomes (11)

• Efficacy Evaluation of MASLD in fibrosis

  From enrollment to the treatment at 24 and 48 weeks

• Efficacy Evaluation of MASLD in liver fatty quantification

  From enrollment to the treatment at 24 and 48 weeks

• Efficacy Evaluation of MASLD in non-invasive biological indicators related to liver fibrosis

  From enrollment to the treatment at 24 and 48 weeks

• Renal function

  From enrollment to the treatment at 24 and 48 weeks

• Liver function

  From enrollment to the treatment at 24 and 48 weeks

Study Arms (2)

Control Group

PLACEBO COMPARATOR

Placebo + Metformin 1.7g/d

Drug: Metformin 1700 mg daily; Other: Placebo of Henagliflozin

Intervention Group

EXPERIMENTAL

Henagliflozin 10mg/d + Metformin 1.7g/d

Drug: Henagliflozin 10 mg daily; Drug: Metformin 1700 mg daily

Interventions

Henagliflozin 10 mg daily DRUG

Henagliflozin (SHR3824) is a hypoglycemic agent classified as an SGLT2i, which has been independently developed by Jiangsu Hengrui Pharmaceutical Co., Ltd. (China) and Shanghai Hengrui Pharmaceutical Co., Ltd (China). It received marketing authorization in China on December 31, 2021 (ID: H20210053).The prescribed dosage of Henagliflozin is 10 mg per day, as indicated on the drug label, with administration recommended in the early morning. In instances where a participant forgot to take the medication in the morning, they were permitted to do so until 12:00 PM on the same day.

Intervention Group

Metformin 1700 mg daily DRUG

The metformin utilized in this study is Metformin Hydrochloride Extended-release Tablets, manufactured by Bristol-Myers Squibb Company. This formulation of metformin is available in a dosage of 0.85 grams per tablet, necessitating that patients administer two tablets daily to acquire the dose of 1.7g daily, to be taken within thirty minutes prior to breakfast and dinner respectively. However, adjustments to the metformin dosage were not permitted during follow-up visits.

Control Group; Intervention Group

Placebo of Henagliflozin OTHER

The placebo was supplied by the pharmaceutical company responsible for Henagliflozin, ensuring that both the placebo and Henagliflozin were indistinguishable in terms of appearance, taste, and odor, while lacking any significant pharmacological effect. Administration of the placebo was recommended to occur in the early morning.

Control Group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must be aged between 18 and 75 years.
• Participants must meet the diagnostic criteria for MASLD and T2DM.
• Participants' HbA1c level between 6.5% and 9%.
• The LSM obtained via the FibroScan device must be equal to or greater than 8 kPa.
• Participants must not have experienced a significant change in body weight exceeding 15% within the past four weeks.
• Participants must not have utilized non-biguanide hypoglycemic medications in the three months preceding the study.

You may not qualify if:

• Patients diagnosed with non-MASLD, which encompasses conditions such as viral hepatitis, autoimmune liver disease, liver tumors, and drug-induced liver injury, among others;
• Individuals exhibiting ALT and/or AST levels that exceed the normal range by threefold or more;
• Patients currently using or having used medications associated with secondary MASLD (including, but not limited to, corticosteroids, estrogen, amiodarone, methotrexate, etc.) within the preceding three months;
• Individuals utilizing or having utilized medications within the last three months that possess the potential to ameliorate hepatic steatosis or fibrosis in MASLD (including, but not limited to, ursodeoxycholic acid, bicyclol tablets, silymarin capsules, polyene phosphatidylcholine capsules, vitamin E, etc.);
• Patients with known or suspected elevated alcohol consumption (females exceeding 12 grams per day; males exceeding 24 grams per day) or those on medications that may contribute to increased consumption;
• Individuals who have experienced severe acute complications such as hypoglycemia, ketoacidosis, hyperglycemia, or hyperosmolar states within the past month or during the course of medication;
• Patients who have undergone metabolic bariatric surgery or are currently participating in bariatric treatment;
• Individuals with significant primary systemic pathologies, including but not limited to respiratory, circulatory, digestive, urinary, neurological, hematological, rheumatological, endocrine diseases, tumors, or AIDS;
• Female participants who are pregnant, breastfeeding, or of childbearing potential and not employing a highly effective contraceptive method;
• Individuals with known allergies or potential allergies to the medications utilized in this study, rendering them intolerant;
• Patients with a history of recurrent or severe urinary and genital tract infections;
• Individuals exhibiting severe cognitive impairment or mental illness that impedes their ability to cooperate;
• Patients currently engaged in clinical observation of other pharmacological agents.

Sponsors & Collaborators

• Xiqiao Zhou: lead
• Jiangsu Hengrui Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

Jiangsu province hospital of traditional chinese medicine

Nanjing, Jiangsu, 210029, China

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Liver Cirrhosis

Interventions

henagliflozin; Metformin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Central Study Contacts

Tiansu Jiangsu province hospital of traditional chinese medicine

CONTACT

025-17397952085; 728294997@qq.com

TIANSU LV, -

CONTACT

025+17397952085

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: In the process of randomizing groups, the study designers assigned a blinded code to each participant. This coding is organized based on the order of enrollment.Only the study implementer will have access to the serial numbers of the study subjects, the blinded codes, and the drugs labeled with those codes. The details of the blind codes are known solely to the lead study designers and are maintained by designated personnel. At this stage, as the study implementer includes participants in sequence, only the drugs labeled with the corresponding codes can be administered, ensuring that neither the implementer nor the participants are aware of the group assignments or the drugs being used.To assess the quality of blinding completion, we employed the James Blinding Index (JBI) and the Bang Blinding Index (BBI) as evaluative tools.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: January 7, 2025
• Study Start: December 31, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 7, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)