1984. Effects of Semaglutide on Adipose Tissue in HIV-Associated Lipohypertrophy

Abstract

Abstract Background Lipohypertrophy (central adipose tissue (AT) accumulation) is a common and significant problem in people with HIV (PWH). Pathogenesis remains elusive; yet, AT abnormalities are key drivers of cardiometabolic co-morbidities in HIV. We aimed to assess effects of semaglutide, a glucagon-like peptide-1 receptor agonist, on AT in PWH with lipohypertrophy. Methods We conducted a randomized, double-blinded, placebo-controlled trial of virologically-suppressed, non-diabetic PWH ≥ 18 years of age on stable antiretroviral therapy (ART) with body mass index (BMI) ≥ 25 kg/m2, increased waist circumference/waist-to-hip ratio, and subjective increased abdominal girth after ART initiation. Participants were randomized 1:1 to 32 weeks semaglutide (8-week titration + 24 weeks 1.0 mg weekly subcutaneous injection) or matching placebo. Computed tomography and whole-body dual-energy X-ray absorptiometry were used to measure area/density in abdominal AT [total (TAT), visceral (TAT), and subcutaneous (SAT)] and body composition [lean body mass (LBM), limb/trunk/total body fat (TBF)], resp. Semaglutide effects were estimated using generalized estimating equations or simultaneous quantile regressions on outcome variables. Results 108 participants were enrolled (N = 54 semaglutide: median age = 52 years, 70% male, 61% Black, 83% integrase inhibitor). Groups were well-matched at baseline. In unadjusted models, semaglutide group had greater reductions (P < 0.05) in BMI, homeostatic model of insulin resistance (HOMA-IR), trunk fat, TBF (at quantile ≥ 75th), TAT, and SAT with trends (P < 0.1) for limb fat and VAT (Fig 1/Table 1). Semaglutide effects remained significant for BMI, HOMA-IR, trunk fat, TAT, and VAT after adjusting for age, sex, CD4, and ART duration (Table 2); caloric intake was also significant at ≤ 50th quantile. No differences were seen in LBM, AT density, or VAT/TAT ratio. Semaglutide was well-tolerated; serious adverse events were rare. Conclusion Semaglutide significantly decreased central fat in PWH with lipohypertrophy, primarily driven by reductions in VAT. Semaglutide may offer an effective treatment to decrease visceral adiposity and reduce co-morbidity risk. Further investigation is needed to determine mechanisms by which reductions in visceral adiposity occur. Disclosures Grace A. McComsey, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Janssen: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Grant/Research Support