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Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial
Open accessAbstract
Background HIV-associated lipohypertrophy, which is characterised by an abnormal accumulation of abdominal visceral adipose tissue, remains problematic in people with HIV. Effective interventions are lacking, despite HIV-associated lipohypertrophy carrying a substantial risk of cardiometabolic comorbidity. The primary aim of this trial was to investigate effects of the GLP-1 receptor agonist, semaglutide, on adipose tissue in HIV-associated lipohypertrophy. Methods This randomised, double-blind, placebo-controlled phase 2b clinical trial was conducted at a single US site. Key inclusion criteria included people with HIV aged 18 years or older with controlled HIV-1, a BMI of 25 kg/m 2 or more, and lipohypertrophy but without type 1 or type 2 diabetes. Participants were randomly assigned 1:1 to receive 32 weeks of once-weekly subcutaneous semaglutide (8-week dose titration and 24 weeks at 1·0 mg) or placebo; all research personnel and participants remained masked to treatment assignment. Primary outcomes were changes at 32 weeks in adipose tissue quantity by body compartment. Analyses, including safety, were performed using intention-to-treat principles. This trial was registered ClinicalTrials.gov (NCT04019197) and is complete. Findings Between June 10, 2019, and July 28, 2022, 108 participants were randomly assigned to receive semaglutide (n=54) or placebo (n=54). Eight (15%) in each group withdrew prematurely. Significant effects of semaglutide were seen over the 32-week study period in sex-adjusted multiplicative regression analyses for the primary outcome, abdominal visceral adipose tissue (β -30·82 cm 2, 95% CI -50·13 to -11·51; % change -30·6%). Decreases were also seen in other key measures, including abdominal subcutaneous adipose tissue (β -42·01 cm 2, 95% CI -75·49 to -8·52; % change -11·2%) and total body fat (natural logarithmic -0·21 kg, 95% CI -0·33 to -0·08; % change -18·9%). There were no statistically significant differences in possibly related or related adverse events (absolute risk difference 0·1111, 95% CI -0·0727 to 0·2869); however, one semaglutide-related grade 4 elevated lipase and two possibly related cases of cholelithiasis (grades 1 and 2) were observed. Interpretation Semaglutide holds promise as an effective treatment for HIV-associated lipohypertrophy. The potential risk of serious adverse events deserves further scrutiny in large trials in people with HIV. Funding National Institutes of Health.
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Emerging evidence suggests that semaglutide may improve metabolic outcomes independent of weight reduction in partial lipodystrophy.
“Emerging evidence suggests that semaglutide may improve metabolic outcomes independent of Weight reduction.”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [152]
The Results report improvements in glucose metabolism, insulin resistance, and some lipid measures. But the study also reports weight and fat loss; it does not establish that the metabolic improvements occurred independently of weight reduction. Its participants had HIV-associated lipohypertrophy, not a defined partial-lipodystrophy population. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn a phase 2b randomized placebo-controlled trial, semaglutide 2.4 mg once weekly significantly reduced abdominal visceral, subcutaneous, and total body fat in people with HIV-associated lipohypertrophy without diabetes.
“In a phase 2b randomized placebo-controlled trial, semaglutide 2.4 mg OW significantly reduced abdominal visceral, subcutaneous, and total body fat in people with HIV-associated lipohypertrophy without diabetes [152]”
From Precision obesity medicine: A phenotype-guided framework for pharmacologic therapy across the lifespan (2025) · cites this paper as [152]
The Methods describe a phase 2b placebo-controlled trial in people with HIV-associated lipohypertrophy without diabetes, and the Findings report reductions in abdominal visceral and subcutaneous fat and total body fat. However, participants received 1.0 mg of semaglutide weekly after dose titration, not 2.4 mg. (LLM, conf=0.95)
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References 31 · Cited by 55
Research works printed but not linked: 21
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Metadata
- Authors
- Eckard, A. R., Wu, Q., Sattar, A., Ansari-Gilani, K., Labbato, D., Foster, T., Fletcher, A. A., Adekunle, R. O., & McComsey, G. A.
- Affiliations
- Medical University of South Carolina (US)
- Case Western Reserve University (US)
- University Hospitals of Cleveland (US)
- Corresponding author
- Eckard, Allison Ross
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2024-08
- Volume
- 12
- Issue
- 8
- Pages
- 523-534
- ISSN
- 2213-8587 (ISSN-L)
- PMC
- PMC11417641
- OpenAlex
- W4400178611
- Cited by
- 55
- References
- 31
- Citations by year
- 2026: 28 · 2025: 17 · 2024: 10
- FWCI
- 29.77
- Type
- journal article
- Language
- en
- Update notices
- erratum (2025-04-01)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 175 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- The Lancet Diabetes & Endocrinology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- Case Western Reserve University Clinical and Translational Science Collaborative (UM1TR004528)
- National Center for Advancing Translational Sciences
- National Institutes of Health (R01DK121619)
- Topics
- Health Sciences › Medicine › Infectious Diseases › HIV-related health complications and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- semaglutide, GLP-1 receptor agonists, visceral adipose tissue, subcutaneous adipose tissue, fat mass, HIV, obesity, cardiometabolic risk, weight loss, dose titration, adverse events, drug safety, body composition, HIV-associated lipodystrophy
- MeSH terms
- Semaglutide, Adult, Double-Blind Method, Glucagon-Like Peptides, Female, Humans, Male, Middle Aged, HIV Infections, Treatment Outcome, HIV-Associated Lipodystrophy Syndrome, Intra-Abdominal Fat
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