Efficacy Study of Liraglutide vs.Sitagliptin vs. Glargine on Liver Fat in T2DM Subjects

Phase 4

Completed

• Conditions: Non-alcoholic Fatty Liver Disease
• Interventions: Drug: Sitagliptin combined with metformin; Drug: Liraglutide combined with metformin; Drug: Insulin glargine combined with metformin

• Registration Number: NCT02147925
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The aim of this study is to explore the effectiveness of liraglutide combined with metformin in non-alcoholic fatty-liver disease patients with type 2 diabetes mellitus (T2DM) compared to sitagliptin and insulin glargine in combination with metformin.

Detailed Description

This is a 26-week, randomized, open-label, active controlled, parallel group, multi-centre trial.To compare the change of intrahepatic lipids (IHL) as measured by magnetic resonance spectroscopy(MRS) or MRI estimated proton density fat fraction (MRI-PDFF) as measured by MRI IDEAL IQ (Iterative Decomposition of water andfat with Echo Asymmetryand Least-squares estimation) in type 2 diabetic patients with non-alcoholic fatty-liver disease after a 26-week treatment of liraglutide, sitagliptin or insulin glargine per day combined with metformin.The primary endpoint will be defined by intrahepatic lipids (IHL) as measured by magnetic resonance spectroscopy (MRS) or MRI-PDFF as measured by MRI IDEAL IQ.

Study Timeline

• Study First Submitted: 2014-05-16
• Study First Submitted QC: 2014-05-27
• Study First Posted: 2014-05-28
• Study Start: 2014-08
• Primary Completion: 2017-04
• Study Completion: 2017-04
• Status Verified: 2017-10
• Last Update Submitted: 2018-05-17
• Last Update Posted: 2018-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

• Recorded Type 2 diabetes diagnosed at least 3 months before the study; At least 3 months treatment on a stable dose（≧1500mg/d）of metformin before the study
• 6.5%<HbA1c ≤10%
• Clinically diagnosed simple liver steatosis
• 30-75 years old
• Female subjects should be postmenopausal, surgically sterile, or using contraceptives for 3 months before screening and continuing throughout the study;
• BMI 20~35 kg/m2 and with a history of stable body weight (≤10%variation for ≥3 months)
• intrahepatic lipids (IHL) >10%

Exclusion Criteria

• Type 1 diabetes
• Treatment within the last 3 months with Thiazolidinediones(TZDs), orlistat, insulin, any history of incretin based therapy or any other drugs associated with hepatic steatosis (including but not limited to glucocorticoids, tamoxifen, amiodarone or methotrexate)
• History or current episode of pancreatitis or other disease of the pancrea; Impaired liver function, defined as plasma alanine transaminase(ALT) >2.5 times of upper normal limit
• Moderate and severe renal insufficiency defined as MDRD formula glomerular filtration rate<60ml/min/1.73m2
• Weekly alcohol intake>14 units for women or >21 units for men
• Any history of liver disease including metabolic or auto-immune liver diseases or viral hepatitis
• History or family history of medullary thyroid cancer(MTC), or multiple endocrine neoplasia type 2(MEN-2)
• Congestive heart failure(NYHA III~IV)
• Severe gastric-intestinal diseases
• Pregnancy and/or intention of becoming pregnant
• Known proliferative retinopathy or maculopathy requiring acute treatment as judged by the Investigator; Use of non-herbal Chinese medicine or other non-herbal local medicine with unknown/unspecified content. Herbal traditional Chinese medicine or other local herbal medicines may, at the Investigator's discretion, be continued throughout the trial at an unchanged dose

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sitagliptin	Sitagliptin combined with metformin	Sitagliptin combined with metformin
Liraglutide	Liraglutide combined with metformin	Liraglutide combined with metformin
Insulin glargine	Insulin glargine combined with metformin	Insulin glargine combined with metformin

Primary Outcome Measures

Name	Time	Method
Intrahepatic lipids (IHL)	26-week	To compare the change of intrahepatic lipids (IHL) in type 2 diabetic patients with non-alcoholic fatty-liver disease after a 26-week treatment of liraglutide, sitagliptin or insulin glargine per day combined with metformin.

Secondary Outcome Measures

Name	Time	Method
Change of abdominal subcutaneous adipose tissue(SAT)	26 weeks	To compare the change of SAT in type 2 diabetic patients
Change of visceral adipose tissue(VAT)	26 weeks	To compare the change of VAT in type 2 diabetic patients
Change in hemoglobin A1c(HbA1c)	26 weeks	To compare the change of HbA1c in type 2 diabetic patients

Trial Locations

Locations (1)

The Third Affiliated Hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China