背景:HIV相关的脂肪肥大,其特征是腹部内脏脂肪组织的异常积累,在艾滋病毒感染者中仍然存在问题。缺乏有效的干预措施,尽管HIV相关的脂肪肥大携带心脏代谢合并症的重大风险。该试验的主要目的是研究GLP-1受体激动剂的作用。塞马鲁肽,与HIV相关的脂肪肥大的脂肪组织。
方法:这是随机的,双盲,安慰剂对照的2b期临床试验在美国的一个研究中心进行.主要纳入标准包括18岁或以上的HIV感染者,HIV-1得到控制,BMI为25kg/m2或以上,和脂肪肥大,但没有1型或2型糖尿病。参与者被随机分配为1:1,接受32周的每周一次皮下semaglutide(8周剂量滴定和24周1·0mg)或安慰剂;所有研究人员和参与者对治疗分配保持掩盖。主要结果是在32周时,身体区室脂肪组织数量的变化。分析,包括安全,使用意向治疗原则进行。该试验已注册ClinicalTrials.gov(NCT04019197),已完成。
结果:在2019年6月10日至2022年7月28日之间,108名参与者被随机分配接受司马鲁肽(n=54)或安慰剂(n=54)。每组有8人(15%)过早退出。在32周的研究期间,在主要结局的性别调整乘性回归分析中观察到司马鲁肽的显着影响。腹部内脏脂肪组织(β-30·82cm2,95%CI-50·13至-11·51;%变化-30·6%)。其他关键措施也有所减少,包括腹部皮下脂肪组织(β-42·01cm2,95%CI-75·49至-8·52;%变化-11·2%)和总体内脂肪(自然对数-0·21kg,95%CI-0·33至-0·08;%变化-18·9%)。可能相关或相关的不良事件无统计学差异(绝对风险差异0·1111,95%CI-0·0727至0·2869);然而,观察到1例司马鲁肽相关的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)。
结论:塞马鲁肽有望成为治疗HIV相关脂肪肥大的有效药物。严重不良事件的潜在风险值得在艾滋病毒感染者的大型试验中进一步审查。
背景:美国国立卫生研究院。
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/m2 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.
RESULTS: 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 cm2, 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 cm2, 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.
CONCLUSIONS: 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.
BACKGROUND: National Institutes of Health.