Effects of iGlarLixi Versus iGlar on Liver Fat Content in Patients With Type 2 Diabetes Mellitus Combined With Metabolic Dysfunction-associated Steatotic Liver Disease

Effects of iGlarLixi Versus iGlar on Liver Fat Content in Patients With Type 2 Diabetes Mellitus With Metabolic Dysfunction-associated Steatotic Liver Disease: A Randomized Controlled Trial

This is a single-center, randomized, open-label, controlled clinical trial to compare the effects of a fixed-ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) versus insulin glargine 100 U/mL (iGlar) on liver fat content in patients with Type 2 Diabetes (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). The study includes a 12-week treatment period.

This study is designed as a single-center, randomized, open-label, parallel controlled trial. A total of 36 participants with T2DM and MASLD (defined by MRI-PDFF ≥10%) will be randomized in a 1:1 ratio to receive either once-daily iGlarLixi or iGlar, both in combination with metformin, for 12 weeks. The primary outcome is the change in liver fat content assessed by magnetic resonance imaging proton density fat fraction (MRI-PDFF) from baseline to week 12. Key secondary outcomes include changes in liver enzymes, liver inflammation, fibrosis indices (assessed by transient elastography and FIB-4 index), body composition (weight, BMI, waist circumference, waist-to-hip ratio, and visceral fat area), glycemic control (HbA1c, fasting and postprandial glucose), insulin function, lipid profiles, and uric acid. Safety assessments will include monitoring of hypoglycemic events, gastrointestinal adverse events, and other adverse events.

Inclusion Criteria:

1. Diagnosis of Type 2 Diabetes Mellitus.
2. Diagnosis of MASLD with liver fat content defined by MRI-PDFF ≥ 10%.
3. HbA1c ≥ 9.0% at screening.
4. Body Mass Index (BMI) between 25.0 and 35.0 kg/m², with stable weight (change < 10% in the past 3 months).
5. Stable antidiabetic regimen for at least 3 months prior to screening.

Exclusion Criteria:

• 1. History of excessive alcohol consumption (≥210 g/week for men, ≥140 g/week for women).

  2. Other known causes of chronic liver disease (e.g., viral hepatitis, autoimmune hepatitis, Wilson's disease, hemochromatosis).

  3. Use of medications known to affect liver fat content (e.g., thiazolidinediones, SGLT2 inhibitors, GLP-1 receptor agonists, systemic corticosteroids) within 3 months prior to screening.

  4. Presence of acute infections or diabetic acute complications (e.g., ketoacidosis, hyperosmolar state) within 2 weeks prior to screening.

  5. History of pancreatitis or elevated amylase/lipase > 3 times the upper limit of normal (ULN).

  6. Significant liver impairment (ALT or AST > 3 × ULN). 7. Moderate to severe renal impairment (eGFR < 60 mL/min/1.73m²). 8. Congestive heart failure (NYHA class III-IV). 9. Personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN-2).

  10. Severe gastrointestinal disease. 11. Contraindications to MRI examination. 12. Pregnancy or lactation. 13. Participation in another investigational drug study within 6 months prior to enrollment.

  14. Known hypersensitivity to the study drugs or their excipients.