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. 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 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 () and is complete. 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, 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, 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. 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. National Institutes of Health.

中文翻译：

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HIV 相关脂肪肥大患者每周一次的 semaglutide 治疗：一项随机、双盲、安慰剂对照的 2b 期单中心临床试验


HIV 相关脂肪肥大，其特征是腹部内脏脂肪组织异常积累，在 HIV 感染者中仍然存在问题。尽管 HIV 相关的脂肪肥大具有心脏代谢合并症的重大风险，但缺乏有效的干预措施。该试验的主要目的是研究 GLP-1 受体激动剂 semaglutide 对 HIV 相关脂肪肥大中脂肪组织的影响。这项随机、双盲、安慰剂对照的 2b 期临床试验在美国的一个地点进行。关键纳入标准包括 18 岁或以上、HIV-1 受控、BMI 为 25 kg/m 或更高、脂肪肥大但无 1 型或 2 型糖尿病的 HIV 感染者。参与者被随机分配 1：1 接受 32 周每周一次的皮下注射 semaglutide （8 周剂量滴定和 24 周 1·0 mg） 或安慰剂;所有研究人员和参与者仍然对治疗分配设盲。主要结局是 32 周时按体室划分的脂肪组织数量的变化。使用意向性治疗原则进行分析，包括安全性。此试用版已注册 （） 并且已完成。在 2019 年 6 月 10 日至 2022 年 7 月 28 日期间，108 名参与者被随机分配接受索马鲁肽 （n=54） 或安慰剂 （n=54）。每组 8 例 （15%） 提前退出。在 32 周的研究期间，在性别调整的乘法回归分析中，观察到 semaglutide 对主要结局、腹部内脏脂肪组织 （β -30·82 cm，95% CI -50·13 至 -11·51;% 变化 -30·6%）的显著影响。 其他关键指标也观察到减少，包括腹部皮下脂肪组织（β -42·01 cm，95% CI -75·49 至 -8·52;% 变化 -11·2%）和全身脂肪（自然对数 -0·21 kg，95% CI -0·33 至 -0·08;% 变化 -18·9%）。可能相关或相关的不良事件没有统计学意义差异（绝对风险差 0·1111,95% CI -0·0727 至 0·2869）;然而，观察到 1 例与 semaglutide 相关的 4 级脂肪酶升高和 2 例可能相关的胆石症病例 （1 级和 2 级）。索马鲁肽有望成为治疗 HIV 相关脂肪肥大的有效方法。在 HIV 感染者的大型试验中，严重不良事件的潜在风险值得进一步审查。美国国立卫生研究院。