Body composition, hepatic fat, metabolic, and safety outcomes of Tesamorelin, a GHRH analogue, in HIV-associated lipodystrophy: A meta-analysis of randomized controlled trials.

This meta-analysis pooled data from five randomized controlled trials (RCTs) to evaluate the effects of tesamorelin — a synthetic growth hormone-releasing hormone (GHRH) analogue — compared with placebo in adults living with HIV who have lipodystrophy. The authors conducted a systematic search of five major databases through July 2025 and applied a random-effects meta-analysis model, assessing risk of bias with RoB 2.0 and certainty of evidence using GRADE. The analysis found that tesamorelin was associated with a statistically significant reduction in visceral adipose tissue (mean difference of approximately −27.71 cm²), as well as improvements in hepatic fat content, lean body mass, and IGF-1 levels. The study authors reported that these benefits occurred without clinically significant adverse effects on glucose metabolism or serious safety signals. Limitations of the analysis include the small number of included trials (n=5), potential variability across trial populations and durations, and the inherent constraints of meta-analytic methodology in establishing causality. The findings suggest tesamorelin may offer metabolic and body composition benefits in HIV-associated lipodystrophy, though the authors note the results should be interpreted within the context of the underlying evidence base.

Why this grade: The study is a systematic meta-analysis of multiple RCTs conducted in human participants, representing the highest tier of clinical study design, though the pool of only five trials moderately limits overall certainty.