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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Diabetes Mellitus Type 2; Metabolic Dysfunction-Associated Steatotic Liver Disease
• Intervention / Treatment: Drug: iGlarLixi; Drug: IGlar U100

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210008
      • Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iGlarLixi group; Participants receive iGlarLixi once daily before breakfast for 12 weeks.	Drug: iGlarLixi; The iGlarLixi is administered as a subcutaneous injection once daily within 1 hour before breakfast. The starting dose ranges from 0.1 to 0.2 U/kg, with a maximum daily dose of 20 U (equivalent to 20 U iGlar or 20 μg Lixi). Dose titration is guided by fasting self-monitored plasma glucose (SMPG) levels, with the goal of achieving a target range of 4.4-5.6 mmol/L while avoiding hypoglycemia. All participants continue to receive background metformin therapy throughout the treatment period.
Other: iGlar group; Participants receive iGlar once daily at a fixed time for 12 weeks.	Drug: IGlar U100; The iGlar is administered via subcutaneous injection once daily at a fixed time. The recommended starting dose ranges from 0.1 to 0.2 U/kg. The dose is subsequently titrated to achieve a fasting self-monitored plasma glucose (SMPG) target of 4.4-5.6 mmol/L, with careful attention to avoiding hypoglycemia. Throughout the study, all participants maintain their background metformin therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of liver fat content	The changes of liver fat content were measured by MRI-PDFF	Baseline, 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of body weight	The changes of body weight were measured by InBody-770 equipment.	Baseline, 12 weeks
Changes of lipid metabolism indexes	The changes of lipid metabolism indexes were measured by triglyceride, total cholesterol, high-density and low-density lipoprotein-cholesterol.	Baseline, 12 weeks
Changes of FIB-4 index	The changes of liver fibrosis can be measured by FIB-4 index.	Baseline, 12 weeks
Changes of liver transaminase	The changes of liver transaminase were measured by ALT, AST, γ-GGT.	Baseline, 12 weeks
Changes of liver inflammation index	The changes of liver inflammation index were measured by TE.	Baseline, 12 weeks
Changes of liver stiffness measurement	The changes of liver stiffness measurement were measured by MRE and VCTE.	Baseline, 12 weeks
Changes of body fat	The changes of body fat were measured by InBody-770 equipment.	Baseline, 12 weeks
Changes of muscle mass	The changes of muscle mass were measured by InBody-770 equipment.	Baseline, 12 weeks
Changes of HbA1c	The changes of glucose metabolism indexes were measured by HbA1c.	Baseline, 12 weeks
Changes of plasma glucose	The changes of glucose metabolism indexes were measured by fasting plasma glucose and 2-h postprandial plasma glucose.	Baseline, 12 weeks
Changes of C-peptide	The changes of glucose metabolism indexes were measured by fasting C-peptide and 2-h postprandial C-peptide.	Baseline, 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Hypoglycemic Events	The number and percentage of participants experiencing at least one hypoglycemic event, categorized by severity, will be assessed and compared between treatment groups.	From Baseline to Week 12
Incidence of other adverse events	All adverse events (AEs) will be recorded and summarized, with particular focus on gastrointestinal adverse events (GIAEs) and other specified events. The following data will be collected: the number and percentage of patients with GIAEs, including the type (nausea, vomiting, diarrhea), grading (per CTCAE v5.0), severity, and relationship to the study drug; the number and percentage of patients with other AEs (including allergic reactions, major adverse cardiovascular events [MACE], and pancreatic events).	From Baseline to Week 12

Collaborators and Investigators

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Investigators: Study Director: Yan Bi, Department of Endocrinology, the Affiliated Drum Tower Hospital of Nanjing University Medical School

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2025
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: November 24, 2025
• First Submitted That Met QC Criteria: December 9, 2025
• First Posted (Actual): December 10, 2025

Study Record Updates

• Last Update Posted (Actual): December 10, 2025
• Last Update Submitted That Met QC Criteria: December 9, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2
• Other Study ID Numbers: 2024-325-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No