Once-weekly semaglutide in people with HIV-associated lipohypertrophy: a randomised, double-blind, placebo-controlled phase 2b single-centre clinical trial.

Autor:	Eckard AR; Department of Pediatrics, Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC, USA; Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC, USA. Electronic address: eckarda@musc.edu., Wu Q; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Sattar A; Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA., Ansari-Gilani K; Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Labbato D; Department of Medicine, Division of Infectious Diseases, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Foster T; Department of Medicine, Division of Infectious Diseases, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Fletcher AA; Department of Medicine, Division of Infectious Diseases, University Hospitals Cleveland Medical Center, Cleveland, OH, USA., Adekunle RO; Department of Medicine, Division of Infectious Diseases, Medical University of South Carolina, Charleston, SC, USA., McComsey GA; Department of Medicine, Division of Infectious Diseases, University Hospitals Cleveland Medical Center, Cleveland, OH, USA.
Jazyk:	angličtina
Zdroj:	The lancet. Diabetes & endocrinology [Lancet Diabetes Endocrinol] 2024 Aug; Vol. 12 (8), pp. 523-534. Date of Electronic Publication: 2024 Jul 01.
DOI:	10.1016/S2213-8587(24)00150-5
Abstrakt:	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. Competing Interests: Declaration of interests ARE served as an advisor for Gilead Sciences and Theratechnologies. GAM received consulting fees from Gilead, ViiV, Janssen, Theratechnologies, and Merck. All other authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Databáze:	MEDLINE
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