REALIST

UnknownPhase 4

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

A Multicentre Controlled and Randomized Study Assessing the Effect of Dulaglutide add-on to Dietary Reinforcement Versus Dietary Reinforcement Alone in Patients With Type 2 Diabetes and Carriers of a Non-alcoholic Steatohepatitis

Lead sponsor

Central Hospital, Nancy, France

Asset

Dulaglutide

Subcutaneous · GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

estimated

Study population

MASH / NAFLD / liver fibrosis, Type 2 diabetes

Key I/E criteria

•BMI ≤40•HbA1c ≤9%

Primary endpoint

•MASH resolution, no fibrosis worsening

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03648554

Org study ID2018-002162-38

Secondary IDPSS2018/REALIST-GUERCI/ASsponsor code

Timeline

Milestones

Study first posted2018-08-27actual

Last update posted2019-06-25actual

Study start2019-09-01estimated

Primary completion2023-09-30estimated

Study completion2024-03-30estimated

Assets

Investigational agents

Dulaglutide

Study populations

Who this study enrolls

MASH / NAFLD / liver fibrosisType 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age > 18 years, < 75 years

•Patients with moderately controlled type 2 diabetes under oral antidiabetic drugs (OADs) (i.e. biguanides, sulfonylureas, glinides, alpha-glucosidase inhibitors) at a stable dose since at least 3 months. Standard basal insulin treatments for at least 6 months before inclusion are allowed in addition to predefined authorized OADs.

•7.0%≤HbA1c≤ 9.0% confirmed in two assays over the last six months

•25 <BMI <40 kg/m2

•Patients carriers of confirmed stable non-alcoholic steatohepatitis diagnosed by liver biopsy dating less than six months, with a NAS score ≥ 4 with at least 1 point in each of the categories (steatosis, ballooning and lobular inflammation) and with a fibrosis score greater than stage 1 fibrosis but less than stage 4 fibrosis

•Stable weight during the six months prior to inclusion, i.e. the change in weight must not exceed 5% in the last six months since the last liver puncture biopsy (LPB).

•Person volunteered to participate in the study, informed about study organization and having signed the consent form

•Person affiliated to or beneficiary of a social security plan

•Person undergone the medical examination adapted to research

–At randomization: The diagnosis and the stage of non-alcoholic steatohepatitis must be confirmed after centralized reading of the hepatic histology of the liver puncture biopsy (LPB) performed within six months prior to inclusion, by a pathologist designated for the study.

Exclusion criteria

•Patients who received a treatment with a GLP-1 agonist, SGLT2 inhibitors, Thiazolidinediones (TZDs), hepatoprotective drugs such as silymarine (Legalon®) or Ursodeoxycholic acid (Cholurso®, Delursan®, Ursolvan®), vitamin E or Betaine during the six months prior to inclusion (3 months before the reference biopsy). Any treatment with DPP-4 inhibitors should be stopped on inclusion.

•Patients receiving rapid or short-acting mealtime insulin or premixed insulin in the last 6 months before screening visit

•Type 1 Diabetes

•Patients with idiopathic hemochromatosis

•Patients carriers of hepatitis B or C

•Terminal renal impairment (calculated clearance < 15 ml/min according to the CKD-EPI formula)

•Class III or IV congestive heart failure according to the NYHA classification

•Chronic alcoholism. The investigator while interviewing the patient at the baseline visit assesses alcohol consumption. This consumption must be limited to 30g/day of alcohol for men and 20g/day of alcohol for women

•Hepatic fibrosis with a Kleiner score ≥ F3 (for a score = F3, patients with a platelet count > 120,000 and an albumin concentration > 35 g/l can be included)

•Patients with gastrointestinal bleeding

•History of acute or chronic pancreatitis

•Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma (FMTC), or personal history of non-familial medullary thyroid carcinoma

•Patients who had bariatric surgery

•Patients who received drug treatment for obesity, notably Orlistat, during the last 6 months

•Patients with eating disorders (anorexia nervosa, bulimia nervosa, binge-eating disorder) which may compromise the achievement of dietary reinforcement goals

•Patients with a known allergy or hypersensitivity to the study product or one of its excipients

•Any other condition deemed incompatible with the proper conduct of the study as determined by the investigator

•Patient having participated in another biomedical research with the taking of an experimental drug within 3 months prior to the screening visit or subject under an exclusion period for other biomedical research.

•Woman of childbearing age without effective contraception

•Person referred in articles L.1121-5, L.1121-7 and L.1121-8 of the Public Health Code:

–Pregnant, parturient or breastfeeding woman

–Minor person (non-emancipated)

–Adult person under legal protection (any form of public guardianship)

–Adult person incapable of giving consent

•Person deprived of liberty for judicial or administrative decision, Person under psychiatric care according to articles L. 3212-1 and L. 3213-1.

Endpoints (13)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

MASH / liver

Weight & body composition

Glycemic / diabetes

Cardiometabolic biomarkers

Patient-reported / QoL

Weight & body composition

3 endpoints

Secondary/protocol endpoint

Change in body composition assessed by dual-energy x-ray absorptiometry scans

Time frame:after 52 weeks of treatment

Total fat mass

change from baseline, improvement

Secondary/protocol endpoint

Change in weight

Time frame:after 52 weeks of treatment

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Weight

Time frame:At 24 weeks after completion of the treatment

descriptive, improvement

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Improvement in the glycemic control

Time frame:after 52 weeks of treatment

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

overall glycemic control improvement

Time frame:after 52 weeks of treatment

HbA1c, change

change from baseline, improvement

LOINC 4548-4

MASH / liver

6 endpoints

Primary/protocol endpoint

Responder's proportion difference between the two groups (dulaglutide (TRULICITY®) on top of dietary reinforcement vs. dietary reinforcement alone)

Time frame:after 52 weeks of treatment

MASH resolution, no fibrosis worsening

categorical status, improvement

Secondary/protocol endpoint

Fibrosis Kleiner score

Time frame:after 52 weeks of treatment

change from baseline, improvement

Secondary/protocol endpoint

Fibrosis using Fibrotest score

Time frame:after 52 weeks of treatment

change from baseline, improvement

Secondary/protocol endpoint

Fibrosis marker parameter

Time frame:after 52 weeks of treatment

change from baseline, improvement

Secondary/protocol endpoint

Changes in serum levels of liver enzymes ALT and AST

Time frame:after 52 weeks of treatment

change from baseline, improvement

componentsALT, change, AST, change

Secondary/protocol endpoint

ALT and AST levels

Time frame:At 24 weeks after completion of the treatment

change from baseline, improvement

Cardiometabolic biomarkers

1 endpoint

Secondary/protocol endpoint

Changes in Lipid parameters

Time frame:after 52 weeks of treatment

change from baseline, improvement

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Change in quality of life

Time frame:after 52 weeks of treatment

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.