Effects of Semaglutide in HIV-Associated Lipohypertrophy

NCT04019197 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 2 other identifiers: STUDY20190121R01DK121619
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, double-blinded, placebo-controlled trial designed to assess the effect of the GLP-1 receptor agonist, semaglutide, on visceral and ectopic fat, insulin resistance, inflammation markers, and the downstream effect of cardiovascular risk in people with HIV. The primary endpoints will be visceral and ectopic fat changes over the study period. The secondary endpoints will include changes in markers of inflammation, immune activation, gut integrity, and cardiovascular disease risk assessment.

Conditions

HIV/AIDS; Lipohypertrophy; Obesity

Keywords

HIV; lipohypertrophy; semaglutide; GLP-1 receptor agonist; obesity

Outcome Measures

Primary Outcomes (3)

• Effects of Semaglutide on Quantity of Abdominal Fat (Total, Subcutaneous, Visceral) at Week 32 Compared to Baseline

  Effects of semaglutide will be investigated, including a comparison of changes over time between participants receiving semaglutide vs. placebo, on the amount of abdominal fat (total, subcutaneous, visceral) as measured in area via abdominal CT scan.

  32 weeks

• Effects of Semaglutide on Quantity of Fat (Total Body Fat, Limb Fat, Trunk Fat) at Week 32 Compared to Baseline

  Effects of semaglutide will be investigated, including a comparison of changes over time between participants receiving semaglutide vs. placebo, on the amount of body fat (total body fat, total limb fat, total trunk fat) as measured in mass via whole-body DXA scan.

  32 weeks

• Effects of Semaglutide on Quantity of Ectopic Fat (Total Pericardial Fat) at Week 32 Compared to Baseline

  Effects of semaglutide will be investigated, including a comparison of changes overtime between participants receiving semaglutide vs. placebo, in total pericardial fat as measured by chest CT scan.

  32 weeks

Secondary Outcomes (46)

• Effects of Semaglutide on Liver Fat at Week 32 Compared to Baseline

  32 weeks

• Effects of Semaglutide on Quantity of Lean Body Mass at Week 32 Compared to Baseline

  32 weeks

• Effects of Semaglutide on Quantity of Total Right Psoas Muscle at Week 32 Compared to Baseline

  32 weeks

• Effects of Semaglutide on Quality of Abdominal Fat (Total, Subcutaneous, Visceral) at Week 32 Compared to Baseline

  32 weeks

• Effects of Semaglutide on Quality of Pericardial Fat at Week 32 Compared to Baseline

  32 weeks

Study Arms (2)

Participants with HIV and lipohypertrophy: semaglutide arm

EXPERIMENTAL

Participants with HIV/lipohypertrophy will receive semaglutide 0.25 mg x4 weeks, then semaglutide 0.5 mg x4 weeks, then semaglutide 1.0 mg x24 weeks, then no drug x24 weeks.

Drug: Semaglutide Injectable Product

Participants with HIV and lipohypertrophy: placebo arm

PLACEBO COMPARATOR

Participants with HIV/Lipohypertrophy will receive placebo x32 weeks, then no placebo for 24 weeks.

Drug: Placebo

Interventions

Semaglutide Injectable Product DRUG

semaglutide subcutaneous injection

Also known as: semaglutide, Ozempic

Participants with HIV and lipohypertrophy: semaglutide arm

Placebo DRUG

placebo injection

Also known as: placebo injection, placebos

Participants with HIV and lipohypertrophy: placebo arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥18 years.
• HIV-1 infection as documented by any licensed ELISA test kit and confirmed by Western blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1 RNA, or a second antibody test by a method other than ELISA is acceptable as an alternative confirmatory test.
• Body mass index ≥25 kg/m2.
• Waist circumference and waist-to-hip ratio \>95 cm and \>0.94 cm, respectively, for men, and \>94 cm and \>0.88 cm, respectively, for women occurring in the context of HIV treatment.
• Subjective evidence of increased abdominal girth occurring after initiation of HIV treatment.
• HIV-1 RNA \<400 copies/mL for ≥6 months.
• Receiving a stable antiretroviral regimen for at least the last 12 weeks prior to study entry with cumulative duration of 1 year of treatment at the time of study entry.
• Provision of signed and dated informed consent form and is capable of reading and comprehending the informed consent.
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• All women of child-bearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to start of study medication. WOCBP is defined as any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy), who is not postmenopausal (defined as amenorrhea 12 consecutive months), or is on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone level 35 mIU/mL. Women who are using oral, implanted, or injectable contraceptive hormones or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g., vasectomy), should be considered of child-bearing potential.
• Female subjects who are not of reproductive potential (have reached menopause or undergone hysterectomy, bilateral oophorectomy or tubal ligation) or whose male partner has undergone successful vasectomy with resulting azoospermia or has azoospermia for any other reason, are eligible without requiring the use of contraception. Patient-reported history of menopause, sterilization, and azoospermia is considered acceptable documentation.
• All subjects must not participate in a conception process (e.g. active attempt to become pregnant or to impregnate, sperm donation, in vitro fertilization), and if participating in sexual activity that could lead to pregnancy, the female subject/male partner must use condoms (male or female) in addition to one of the following forms of contraception while on study: either a spermicidal agent, diaphragm, cervical cap, IUD, or hormonal-based contraception.
• Have no plans to alter antiretroviral therapy, or to undergo any weight loss program, formal exercise training or surgery during the study period, or initiate structured/strategic antiretroviral treatment interruptions.

You may not qualify if:

• Known cardiovascular disease or diagnosed diabetes. If on metformin without a diabetes diagnoses metformin use has to be constant, uninterrupted for 6 months prior to entry.
• Any active or chronic uncontrolled inflammatory condition, infection or cancer.
• Women who are pregnant or breastfeeding.
• Women with a positive pregnancy test on enrollment or prior to study drug administration.
• A clinically-relevant illness within 14 days prior to study entry not explicitly excluded by the protocol, a physical or psychiatric disability, or a laboratory abnormality that might place the subject at increased risk by being exposed to the medications in this study or which might confound the interpretation of this investigation.
• Active gastrointestinal symptom Grade \>1 within the last month.
• Regular use of immunomodulators/agents which could impact inflammation. Regular use of NSAIDS allowed if constant, uninterrupted for 6 months and no plans to alter. Statin use must also be constant, uninterrupted for 6 months prior to study entry. Thyroid medication allowed unless diagnosed with uncontrolled thyroid disease.
• Inability to communicate effectively with study personnel.
• Use of megestrol acetate, testosterone, or any steroid use beyond normal amounts found in the body within 6 months of study, or intend to start.
• Glomerular filtration rate \<50 cc/min/1.73 m2.
• Hemoglobin \<10 g/dL.
• Elevated lipase level \>1.5 upper limit of normal
• AST AND ALT \>2.5x upper limit of normal.
• Use of growth hormone or growth hormone-releasing hormone in the last year, or intent to start.
• History of excessive alcohol use (on average 2 or more drinks a day) , pancreatitis, thyroid cancer, or a diagnosis of multiple endocrine neoplasia (MEN) syndrome type 2.

Sponsors & Collaborators

• Case Western Reserve University: lead
• Medical University of South Carolina: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Related Publications (3)

• Atieh O, Daher J, Abboud M, Wu Q, Sattar A, Baissary J, Koberssy Z, Labbato D, Eckard AR, McComsey GA. Effects of Semaglutide on Cognitive Function in People with HIV: A Randomized Controlled Trial. Clin Infect Dis. 2025 Oct 16:ciaf577. doi: 10.1093/cid/ciaf577. Online ahead of print.

  PMID: 41098140 DERIVED

• Funderburg NT, Ross Eckard A, Wu Q, Sattar A, Ailstock K, Cummings M, Labbato D, McComsey GA. The Effects of Semaglutide on Inflammation and Immune Activation in HIV-associated Lipohypertrophy. Open Forum Infect Dis. 2025 Mar 20;12(4):ofaf152. doi: 10.1093/ofid/ofaf152. eCollection 2025 Apr.

  PMID: 40160348 DERIVED

• Eckard AR, Wu Q, Sattar A, Ansari-Gilani K, Labbato D, Foster T, Fletcher AA, Adekunle RO, McComsey GA. Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial. Lancet Diabetes Endocrinol. 2024 Aug;12(8):523-534. doi: 10.1016/S2213-8587(24)00150-5. Epub 2024 Jul 1.

  PMID: 38964353 DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; Obesity

Interventions

semaglutide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Notably, participants were treated with 1.0 mg semaglutide weekly, the US Food and Drug Administration-approved dose at the time of study initiation. Since then, recommended doses have increased to 2.0 mg and 2.4 mg for type 2 diabetes and weight loss, respectively

Results Point of Contact

• Title: Allison Ross Eckard, MD
• Organization: Medical University of South Carolina

eckarda@musc.edu

843-792-4541

Study Officials

• Grace A McComsey, MD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

• Allison R Eckard, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 1, 2019
• First Posted: July 15, 2019
• Study Start: May 16, 2019
• Primary Completion: April 30, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 4, 2026
• Results First Posted: February 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: after completion of total study and publication
• Access Criteria: individual requests will be reviewed by study PIs.

Locations

US (2)