Henagliflozin on Liver Fibrosis in Patients with MASLD and T2DM

Phase 4

Not yet recruiting

• Conditions: Metabolic Dysfunction-associated Steatotic Liver Disease; Type 2 Diabetes Mellitus
• Interventions: Drug: Metformin 1700 mg daily; Drug: Henagliflozin 10 mg daily; Other: Placebo of Henagliflozin

• Registration Number: NCT06762223
• Lead Sponsor: Xiqiao Zhou

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-17
• Study Start: 2024-12-31
• Study First Submitted QC: 2025-01-01
• Last Update Submitted: 2025-01-01
• Study First Posted: 2025-01-07
• Last Update Posted: 2025-01-07
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 190

Inclusion Criteria

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

Exclusion Criteria

1. Patients diagnosed with non-MASLD, which encompasses conditions such as viral hepatitis, autoimmune liver disease, liver tumors, and drug-induced liver injury, among others;
2. Individuals exhibiting ALT and/or AST levels that exceed the normal range by threefold or more;
3. 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;
4. 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.);
5. 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;
6. 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;
7. Patients who have undergone metabolic bariatric surgery or are currently participating in bariatric treatment;
8. Individuals with significant primary systemic pathologies, including but not limited to respiratory, circulatory, digestive, urinary, neurological, hematological, rheumatological, endocrine diseases, tumors, or AIDS;
9. Female participants who are pregnant, breastfeeding, or of childbearing potential and not employing a highly effective contraceptive method;
10. Individuals with known allergies or potential allergies to the medications utilized in this study, rendering them intolerant;
11. Patients with a history of recurrent or severe urinary and genital tract infections;
12. Individuals exhibiting severe cognitive impairment or mental illness that impedes their ability to cooperate;
13. Patients currently engaged in clinical observation of other pharmacological agents.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control Group	Metformin 1700 mg daily	Placebo + Metformin 1.7g/d
Control Group	Placebo of Henagliflozin	Placebo + Metformin 1.7g/d
Intervention Group	Henagliflozin 10 mg daily	Henagliflozin 10mg/d + Metformin 1.7g/d
Intervention Group	Metformin 1700 mg daily	Henagliflozin 10mg/d + Metformin 1.7g/d

Primary Outcome Measures

Name	Time	Method
Liver stiffness measurements (LSM) of subjects	From enrollment to the treatment at 24 and 48 weeks	As determined by magnetic resonance elastography (MRE)

Secondary Outcome Measures

Name	Time	Method
Efficacy Evaluation of MASLD in fibrosis	From enrollment to the treatment at 24 and 48 weeks	This includes: 1. Difference from baseline in LSM of subjects based on FibroScan; 2. The proportion of LSM of subjects on MRE reduced by ≥15%; 3. The proportion of LSM of subjects on FibroScan reduced by ≥15%
Efficacy Evaluation of MASLD in liver fatty quantification	From enrollment to the treatment at 24 and 48 weeks	This includes: 1. Difference from baseline in liver fatty quantification of subjects based on magnetic resonance imaging proton density fat fraction(MRI-PDFF); 2. Difference from baseline in liver fatty quantification of subjects based on FibroScan; 3. The proportion of liver fatty quantification of subjects based on MRI-PDFF was reduced by ≥30%; 4. The proportion of liver fatty quantification of subjects based on FibroScan was reduced by ≥30%;
Efficacy Evaluation of MASLD in non-invasive biological indicators related to liver fibrosis	From enrollment to the treatment at 24 and 48 weeks	This includes:1.NAFLD fibrosis score(NFS) = - 1.675 + \[0.037 ×Age\] + \[0.094 × body mass index(BMI) (kg/m2)\] + \[1.13 × fasting plasma glucose(FPG)/ Diabetes (Yes=1，No= 0)\] + \[0.99 × aspartate aminotransferase(AST)/alanine aminotransferase(ALT)\] - \[0.013 × platelet count(PLT) (×109/L)\] - \[0.66 × Albumin(ALB) (g/dL)\]; NFS \<-1.455, -1.455-0.675, and \>0.675 mean expressed as low, medium, and high risk, respectively(39); 2.Fibrosis-4(FIB-4) index= \[Age× AST (U/L)\]/\[PLT (×109/L)× ALT (U/L)1/2\];
Renal function	From enrollment to the treatment at 24 and 48 weeks	This includes:This includes:Difference from baseline in renal function related parameters of subjects, primarily including uric acid(UA), urea nitrogen(BUN), creatinine(Cr), urine albumin-to-creatinine ratio(UACR).
Liver function	From enrollment to the treatment at 24 and 48 weeks	This includes:Difference from baseline in liver function related parameters of subjects, primarily including AST, ALT, gamma-glutamyl transferase(GGT), alkaline phosphatase(ALP), ALB, total bilirubin(TBiL).
Lipid metabolism	From enrollment to the treatment at 24 and 48 weeks	This includes:Difference from baseline in lipid metabolism related parameters of subjects, primarily including Triglyceride(TG), total cholesterol(TC), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C).
Efficacy Evaluation of T2DM	From enrollment to the treatment at 24 and 48 weeks	homeostatic model assessment of insulin resistance(HOMA-IR)

Trial Locations

Locations (1)

Jiangsu province hospital of traditional chinese medicine; 🇨🇳 Nanjing, Jiangsu, China