Study of Semaglutide for Non-Alcoholic Fatty Liver Disease (NAFLD), a Metabolic Syndrome With Insulin Resistance, Increased Hepatic Lipids, and Increased Cardiovascular Disease Risk (The SLIM LIVER Study)

NCT04216589 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: ACTG A537138453
• Study Type: interventional
• Target: 51
• Locations: 2 countries
• Sites: 9

Brief Summary

The purpose of this study was to evaluate the effects of semaglutide on intra-hepatic triglyceride (IHTG) content in people living with HIV (PLWH), central adiposity, insulin resistance or pre-diabetes, and hepatic steatosis.

Conditions

HIV Infections; Non-Alcoholic Fatty Liver Disease

Keywords

NAFLD; HIV; semaglutide

Outcome Measures

Primary Outcomes (1)

• Change (Absolute) in IHTG (%)

  The absolute change in intra-hepatic triglyceride content (%), as quantfied by MRI-PDFF, from the pre-entry visit to the Week 24 visit.

  Measured at pre-entry and Week 24

Secondary Outcomes (24)

• Change (Percent) in IHTG (%)

  Measured at pre-entry and Week 24

• Level of IHTG (%)

  Measured at Week 24

• Occurrence of Premature Discontinuation of Study Treatment

  Measured through Week 24

• Occurrence of Grade ≥3 Adverse Event That is Related to Study Treatment

  Measured through Week 24

• Change (Absolute) in Body Mass Index (BMI)

  Measured at Week 0 and Week 24

Study Arms (1)

Semaglutide

EXPERIMENTAL

All participants received a dose of 0.25 mg of semaglutide weekly starting at study entry, followed by 0.5 mg weekly starting at Week 2, and then 1.0 mg weekly from Weeks 4 through 24.

Drug: Semaglutide

Interventions

Semaglutide DRUG

Administered subcutaneously

Semaglutide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.
• NOTE: The term "licensed" refers to a US Food and Drug Administration (FDA)-approved kit, which is required for all investigational new drug (IND) studies, or for sites located in countries other than the United States, a kit that has been certified or licensed by an oversight body within that country and validated internally. Non-US sites are encouraged to use US FDA-approved methods for IND studies.
• WHO (World Health Organization) and CDC (Centers for Disease Control and Prevention) guidelines mandate that confirmation of the initial test result must use a test that is different from the one used for the initial assessment. A reactive initial rapid test should be confirmed by either another type of rapid assay or an E/CIA that is based on a different antigen preparation and/or different test principle (e.g., indirect versus competitive), or a Western blot or a plasma HIV-1 RNA viral load.
• Two separate reports of HIV-1 RNA measurements \<50 copies/mL, and no HIV-1 RNA measurement \>500 copies/mL, during the 48 weeks prior to entry. One of the HIV-1 RNA values must be the screening visit value, and the other value obtained between 24 and 48 weeks prior to entry.
• NOTE: All values must have been reported from a US laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent, or at any network-approved non-US laboratory that is Virology Quality Assurance (VQA) certified.
• No change in antiretroviral therapy (ART) in the 24 weeks prior to entry.
• NOTE A: Modifications of ART formulation (e.g., from standard formulation to fixed dose combination or single tablet regimen) will be permitted.
• NOTE B: Within-class substitutions are not permitted.
• No plan to change ART for the study duration.
• Within 30 days prior to pre-entry, a minimum WC measurement of ≥95 cm for individuals assigned male sex at birth or ≥94 cm for individuals assigned female sex at birth.
• NOTE: For transgender study participants, sites should use the parameter that matches sex assigned at birth.
• At least one of the following drawn within 30 days prior to pre-entry by any US laboratory that has a CLIA certification or its equivalent, or at any network-approved non-US laboratory that operates in accordance with Good Clinical Laboratory Practices (GCLP) and participates in appropriate external quality assurance programs:
• Fasting plasma glucose 100-125 mg/dL (refer to the study protocol for a definition of fasting).
• HbA1c between ≥5.7 and \<6.5%
• Homeostatic model assessment of insulin resistance (HOMA-IR) \>3.0 (Refer to calculator: https://www.mdcalc.com/homa-ir-homeostatic-model-assessment-insulin-resistance)

You may not qualify if:

• Known active hepatitis C virus (HCV) infection, defined as a detectable HCV RNA within 24 weeks prior to study entry.
• NOTE A: Individuals with HCV RNA below the limit of quantitation for \>24 weeks prior to study entry are eligible, i.e., individuals who have been treated for hepatitis C are eligible if they have completed therapy \>24 weeks prior to study entry, and/or individuals who spontaneously cleared hepatitis C virus are eligible as long as they have had undetectable HCV RNA for \>24 weeks. HCV RNA testing is not provided by the study.
• NOTE B: If HCV antibody testing has not been performed in the 5 years prior to screening and the participant does not have history of cured HCV infection, HCV antibody testing should be repeated at screening. If screening HCV antibody is positive or reactive, the individual is not eligible and should be referred for clinical evaluation through routine care.
• Active/chronic hepatitis B (HBV), defined as a positive hepatitis B surface antigen (HBsAg) at screening.
• NOTE A: HBsAg testing is only required at screening if HBV laboratory results are not available within the last 5 years prior to screening and individual does not have documented immunity.
• NOTE B: If HBsAg positive, individual is not eligible and should be referred for clinical evaluation through routine care.
• Known active severe delayed gastric emptying, as determined by the site investigator.
• Gain or loss of \>5% body weight within 12 weeks prior to study entry.
• NOTE: Self-report recall is acceptable.
• Any plans to change diet or exercise regimen significantly, except for the adoption of study provided suggestions for diet and exercise, within the study period.
• NOTE: "Significantly" refers to intent to join a weight-loss program such as Weight Watchers, or start a specific diet (such as ketogenic or very low carbohydrate).
• Known acute or chronic liver disease with cirrhosis or portal hypertension.
• History of liver transplant.
• Breastfeeding or plans to become pregnant.
• Current diagnosis of diabetes mellitus or current use of diabetes medications, or a laboratory measurement of hemoglobin A1c ≥6.5% at screening.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• The University of Texas Health Science Center, Houston: collaborator

Study Sites (9)

Alabama CRS (Site ID: 31788)

Birmingham, Alabama, 35294, United States

Location

University of Colorado Hospital CRS (Site ID: 6101)

Aurora, Colorado, 80045, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital CRS (MGH CRS) (Site ID: 101)

Boston, Massachusetts, 02114, United States

Location

Cincinnati Clinical Research Site (Site ID: 2401)

Cincinnati, Ohio, 45267-0405, United States

Location

Ohio State University CRS (Site ID: 2301)

Columbus, Ohio, 43210, United States

Location

Houston AIDS Research Team CRS (Site ID: 31473)

Houston, Texas, 77009, United States

Location

University of Washington AIDS CRS (Site ID: 1401)

Seattle, Washington, 98104-9929, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (IPEC) CRS (Site ID: 12101)

Rio de Janeiro, 21040-360, Brazil

Location

Related Publications (2)

• Corley M, Pang A, Kitch D, Kantor A, Sattler F, Belaunzaran-Zamudio P, Brown T, Landay A, Lake J, Erlandson K. Epigenetic Aging and Treatment Response to Semaglutide in the SLIM LIVER Study. Res Sq [Preprint]. 2025 Oct 1:rs.3.rs-7697256. doi: 10.21203/rs.3.rs-7697256/v1.

  PMID: 41256006 DERIVED

• Ditzenberger GL, Lake JE, Kitch DW, Kantor A, Muthupillai R, Moser C, Belaunzaran-Zamudio PF, Brown TT, Corey K, Landay AL, Avihingsanon A, Sattler FR, Erlandson KM. Effects of Semaglutide on Muscle Structure and Function in the SLIM LIVER Study. Clin Infect Dis. 2025 Feb 24;80(2):389-396. doi: 10.1093/cid/ciae384.

  PMID: 39046173 DERIVED

Related Links

• The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017.
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010.

MeSH Terms

Conditions

HIV Infections; Non-alcoholic Fatty Liver Disease

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• Kristine Erlandson, MD, MS

  University of Colorado Hospital CRS

  STUDY CHAIR

• Jordan E. Lake, MD, MSc

  Houston AIDS Research Team CRS

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2019
• First Posted: January 2, 2020
• Study Start: February 19, 2021
• Primary Completion: March 16, 2023
• Study Completion: September 15, 2023
• Last Updated: October 1, 2024
• Results First Posted: May 17, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? * Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? * To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? * Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://submit.mis.s-3.net/ Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (8); BR (1)