Background:
Among recent concerns surrounding weight gain in people with HIV (PWH) is the increasing incidence of Metabolic Syndrome (MetS). MetS, a component of which is central adiposity, is associated with increased risk of cardiovascular disease, stroke, and type 2 diabetes in PWH. Tesamorelin, a growth hormone releasing hormone analogue, was previously shown to reduce visceral adipose tissue (VAT) by over 15% in 26 weeks in PWH with lipohypertrophy. Due to the association between excess VAT and MetS, we investigated whether treatment with tesamorelin was also associated with changes in MetS classification
Methods:
We leveraged data from 2 Phase III trials of tesamorelin among PWH with excess VAT. Participants were randomized to receive tesamorelin (2 mg) or placebo subcutaneously daily for 26 weeks. In a per-protocol analysis of 400 participants assigned to receive tesamorelin, responders (R) were defined a priori by ≥8% reduction in VAT. Participants were evaluated and classified for MetS longitudinally by its 5 components – elevated waist circumference, high triglycerides, low HDL cholesterol, increased blood pressure, and elevated fasting blood glucose – according to both NCEP and IDF guidelines. Post hoc analyses were then performed to assess changes in MetS classification between responders and non-responders
Results:
The prevalence of MetS was high at baseline among study participants (37%) and did not significantly differ between responders (R) and non-responders (NR) (R: 34.2%; NR: 43.8% by NCEP; p=0.077). However, following 26 weeks of tesamorelin treatment, the prevalence of MetS decreased in responders resulting in a significantly lower prevalence of MetS compared to non-responders (R: 30.8%; NR: 48.5%; p< 0.001). While the overall prevalence of MetS by IDF was lower than under NCEP guidelines, the treatment effect of tesamorelin remained consistent (data not shown; p< .0001). Differences in MetS status were driven predominantly by resolution of triglycerides (R: 26.3%; NR: 5.0% p=0.005) and waist circumference (R: 25.6%; NR: 10.0%; p=0.031)
Conclusions:
These data suggest that VAT reduction with tesamorelin is associated with a reversal of MetS classification among PWH. This is consistent with previous data indicating that visceral fat reduction is associated with improvements in metabolic parameters of PWH, and thus supports the use of tesamorelin in PWH with central adiposity to improve metabolic profiles