Background
Lipohypertrophy (central adipose tissue (AT) accumulation) and AT abnormalities are common in people with HIV (PWH) and are key drivers of cardiometabolic comorbidities. In a recent randomized, double-blind, placebo-controlled phase 2b clinical trial, we observed significant effects of the glucagon-like peptide-1 receptor agonist (GLP-1 RA), semaglutide, over 32 weeks on key outcome measures, including improvements in weight, total body fat, visceral adiposity, blood pressure, glucose metabolism, and lipids in PWH and lipohypertrophy. The current analysis investigates effects of semaglutide on measures of subclinical cardiovascular health.
Methods
Virologically-suppressed PWH without known diabetes on stable antiretroviral therapy (ART) with body mass index ≥25 kg/m2, increased waist circumference/waist-to-hip ratio were included. Participants were randomized 1:1 to 32 weeks semaglutide or matching placebo. Pulse wave velocity (PWV), endothelial peripheral artery tonometry (endoPAT), and coronary artery calcium (CAC) score were used to measure arterial stiffness, endothelial function, and calcified coronary atherosclerotic disease, respectively. Indirect calorimetry was used to measure fasting resting energy expenditure (REE) and oxygen consumption (V02), assessments of general cardiometabolic health. 10-year atherosclerotic cardiovascular disease (ASCVD) risk scores were calculated. Analyses were performed with intention-to-treat principles using sex-adjusted multiplicative regression.
Results
108 participants (N=54 semaglutide) were enrolled (median age: 53 years, 60% male, 35% smokers). There were no statistically significant effects of semaglutide on PWV, CAC score, nor endoPAT endpoints, including reactive hyperemia index and augmentation index over the 32-week study period. While there were no statistically significant effects of semaglutide on REE, there was a trend toward significance for V02 [β –43 L/min, 95% confidence interval (CI) –92.3, 6.3; p=0.087; % change +11.3%]. Statistically significant decreases were seen in the 10-year ASCVD risk score (ln β –0.39, CI –0.74, –0.05; p=0.026; % change –32.6%).
Conclusions
32 weeks of semaglutide had no discernible effects on subclinical vascular disease, including arterial stiffness and endothelial function. However, there were improvements in overall cardiometabolic health and cardiovascular disease (CVD) risk. Longer and larger studies of GLP-1 RAs are indicated in HIV to further assess their effects on long-term CVD outcomes.