Semaglutide microdosing trial aims to prevent weight regain and improve cardiometabolic health in PWH

People with HIV (PWH) often face increased risks of cardiometabolic diseases, including obesity, insulin resistance, and dyslipidemia, partly due to antiretroviral therapies and chronic inflammation. Traditional weight loss interventions can be challenging to sustain, leading to high rates of weight regain. GLP-1 receptor agonists, like liraglutide and semaglutide, have demonstrated significant efficacy in weight management and improving cardiometabolic markers in the general population and in PWH, as seen in the prior LIROH trial. However, the optimal dosing strategy for long-term maintenance and tolerability, particularly microdosing, in this vulnerable population remains an important clinical gap.

This is a randomized, controlled, parallel-group, open-label study enrolling 80 HIV-1 infected patients aged ≥ 18 years with a BMI ≥30 kg/m². Participants will undergo an initial 12-week weight loss induction phase using standard semaglutide dosing, followed by a 48-week maintenance phase. During maintenance, the intervention arm will receive semaglutide microdosing in combination with lifestyle interventions, while the control arm will receive lifestyle interventions alone. The primary endpoint is the rate of weight regain, with secondary objectives evaluating tolerability and changes in weight, waist circumference (WC), and body mass index (BMI) over the 60-week study duration.

This study is a trial protocol, and as such, no findings or numerical results are available yet. The primary objective is to prospectively determine the rate of weight regain in PWH receiving semaglutide microdosing versus no additional drug following an initial weight loss induction therapy. Secondary objectives will evaluate the tolerability of semaglutide microdosing in this population, which is crucial given potential drug interactions and comorbidities in PWH. Furthermore, the trial aims to quantify changes in key anthropometric measures, specifically weight, WC, and BMI, over the 12-week induction phase and the subsequent 48-week microdosing maintenance period.

The study is designed to provide critical data on the long-term efficacy and safety of a novel semaglutide dosing strategy for weight management in PWH, addressing a significant unmet need in cardiometabolic health for this specific patient group. The results will indicate whether a microdosing approach can effectively sustain weight loss and improve cardiometabolic health markers without the higher incidence of adverse events sometimes associated with full-dose GLP-1R agonists.