Endocrinology · Medical Literature
Efficacy and Safety of Tesamorelin in People Living With HIV (PLWH) With Lipodystrophy: A Systematic Review and Meta-Analysis.
Abstract
BackgroundHIV-associated lipodystrophy, a complication of combined antiretroviral therapy (CART), causes significant physical and psychological distress in people living with HIV (PLWH), compromising treatment adherence. Tesamorelin, a growth hormone-releasing hormone (GHRH) analogue, has emerged as a therapeutic option.ObjectiveTo systematically evaluate the efficacy and safety of tesamorelin in HIV-infected individuals with lipodystrophy receiving CART, incorporating GRADE assessment.MethodsWe searched PubMed, https://ClinicalTrials.gov, and Scopus from inception to February 9, 2026, for randomized controlled trials evaluating tesamorelin in HIV-associated lipodystrophy. Mean differences (MD) and risk ratios (RR) with 95% confidence intervals (CI) were calculated using random-effects models with heterogeneity assessed by I2.ResultsFour RCTs (909 patients) were included. Tesamorelin 2mg significantly reduced visceral adipose tissue (MD= -21.47, 95%CI[-34.73,-8.22],I2=74%,p=0.002), waist circumference (MD-1.61cm,95% CI[-2.28,-0.95],I2=0%,p<0.00001), trunk fat (MD-1.20kg, 95%CI[-1.47,-0.93],I2=0%,p<0.00001), and increased lean body mass (MD1.42kg,95% CI[1.13,1.71],I2=0%,p<0.00001). Modest lipid improvements occurred in total cholesterol (MD-0.16mmol/L,95%CI[-0.27,-0.06],I2=0%,p=0.003). Growth hormone-related adverse effects and higher discontinuation rates (RR2.25,95%CI[0.98,5.17],p=0.06) were observed.ConclusionsTesamorelin demonstrates efficacy in reducing visceral adiposity in PLWH with lipodystrophy on CART. However, limited data on long-term safety, optimal dosing strategies, and durability of treatment effects warrant caution. Future research should evaluate extended treatment duration, dose-response relationships, and patient-reported outcomes to establish comprehensive clinical utility.
Clinical relevance
HIV-associated lipodystrophy, a well-recognized metabolic complication of combined antiretroviral therapy (CART), causes visceral fat accumulation with significant physical disfigurement and psychological burden, often compromising ART adherence in PLWH. Despite tesamorelin's FDA approval for this indication, consolidated high-quality evidence synthesizing its efficacy and safety across randomized controlled trials had been lacking. This systematic review and meta-analysis of 4 RCTs (n=909) provides the most rigorous GRADE-assessed quantitative summary to date, directly informing endocrinologists and HIV medicine specialists managing this challenging comorbidity.
Key findings
1. Tesamorelin 2mg daily produced a statistically significant reduction in visceral adipose tissue (VAT) compared to placebo (MD = −21.47 cm², 95% CI [−34.73, −8.22]; I² = 74%; p = 0.002), though moderate heterogeneity warrants cautious interpretation. 2. Waist circumference was significantly reduced with tesamorelin (MD = −1.61 cm; 95% CI [−2.28, −0.95]; I² = 0%; p < 0.00001), with no heterogeneity across trials. 3. Trunk fat mass was significantly decreased (MD = −1.20 kg; 95% CI [−1.47, −0.93]; I² = 0%; p < 0.00001), indicating consistent and meaningful reduction in central adiposity. 4. Lean body mass increased significantly with tesamorelin (MD = +1.42 kg; 95% CI [+1.13, +1.71]; I² = 0%; p < 0.00001), suggesting a favorable body composition shift beyond fat redistribution alone. 5. A modest but statistically significant reduction in total cholesterol was observed (MD = −0.16 mmol/L; 95% CI [−0.27, −0.06]; I² = 0%; p = 0.003), though the clinical magnitude is limited. 6. Discontinuation rates were numerically higher in the tesamorelin group (RR = 2.25; 95% CI [0.98, 5.17]; p = 0.06), falling just short of statistical significance, alongside growth hormone-related adverse effects (e.g., fluid retention, arthralgias, glucose metabolism perturbations) that require ongoing monitoring.
Practice implications
Tesamorelin 2mg subcutaneously daily should be considered as a targeted therapeutic option for PLWH on stable CART who exhibit clinically significant visceral lipohypertrophy, given its consistent, quantitatively meaningful reductions in VAT, waist circumference, and trunk fat alongside lean mass preservation. Clinicians must proactively monitor for GH-related adverse effects — including peripheral edema, arthralgias, and dysglycemia — and counsel patients that the nearly 2.3-fold higher discontinuation risk, though not statistically significant in this meta-analysis, reflects real-world tolerability concerns that may affect long-term adherence. Given the absence of robust long-term safety data, optimal dosing strategies, and evidence on durability of effect after discontinuation, tesamorelin use should currently be individualized, with periodic reassessment of benefit-risk balance and patient-reported outcomes integrated into follow-up.