Researching an Effect of GLP-1 Agonist on Liver STeatosis (REALIST)

Summary

GLP-1 analogues represent new treatments in diabetes that cause weight loss. Their effect on NASH in humans is unknown. A decrease in Alanine Aminotransferase (ALT) has been reported in pooled Exenatide/Placebo and Liraglutide/Placebo studies. More recently, LEAN study has shown that Liraglutide will result in improvements in liver histology in patients with NASH. It should be of high interest to investigate the effect of another GLP-1 Agonist as effective as Liraglutide, i.e. Dulaglutide in NASH.

Dulaglutide is one of the five GLP-1 receptor agonists approved for type 2 diabetes mellitus (T2DM). It is an effective treatment because it is dosed once-weekly, provides HbA1c reduction similar to Liraglutide, weight reduction similar to Exenatide, and has an adverse effect profile similar to other GLP-1 receptor agonists. Reduction in body weight was observed in patients treated with Dulaglutide, irrespective of nausea and/or vomiting.The search for a direct effect of Dulaglutide on liver fat overload in patients with type2 diabetes is required before considering the effectiveness of this treatment in NASH in diabetic populations. No current GLP-1 study has been designed with a control group with the same weight loss than as in the treatment group.

Primary objective: The investigators aim to study the effect of Dulaglutide 1.5 mg (TRULICITY®) add-on to dietary reinforcement after 52 weeks of treatment, on the improvement of liver histology compared to dietary reinforcement alone in patients with type 2 diabetes and carriers of non-alcoholic steatohepatitis.

Secondary objectives:

* After 52 weeks of treatment, to assess the effect of dulaglutide (TRULICITY®) add-on to dietary reinforcement on Fibrosis score, Transaminase levels, body composition as measured by dual energy X-ray absorptiometry, lipid profile, glycemic control and weight. The effect of the treatment will also be assessed on quality of life.
* At 24 weeks after completion of the treatment, to assess the sustainability of dulaglutide (TRULICITY®) treatment add-on to dietary reinforcement on ALT and AST rates as well as on weight.

Conditions

• Diabetes Mellitus, Type 2
• NASH - Nonalcoholic Steatohepatitis

Interventions

DRUG

dulaglutide (TRULICITY®) 1.5 mg

dulaglutide (TRULICITY®) 1.5 mg subcutaneous administration, one weekly injection over 52 weeks of treatment

OTHER

reinforced dietary monitoring

moderate caloric restriction individually adjusted according to the ideal weight and activity level, encouraging regular physical activity (about 30 minutes per day or 150-200 min per week)

Sponsors & Collaborators

• Eli Lilly and Company

  collaborator INDUSTRY

• Central Hospital, Nancy, France

  lead OTHER

Principal Investigators

• Bruno GUERCI · CHRU de Nancy

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-09-01

Primary Completion

2023-09-30

Completion

2024-03-30

Countries

• France

Study Locations