ALT, AST Changes Linked to Glucose Parameters Changes in Tesamorelin-Treated Patients
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HIV-positive (+) patients who were responders to tesamorelin demonstrated changes in liver transminases which were associated with changes in glucose parameters and adiponectin levels, as presented by Jean-Claude Mamputu, PhD, Theratechnologies, Inc. The findings from the pooled analysis were presented at the AACE 2017 Annual Meeting.
Tesamorelin is a synthetic analogue of human growth hormone-releasing hormone and is effective in reducing visceral adipose tissue (VAT) in HIV+ patients with lipodystrophy. Decreased VAT was associated with improvements in liver transaminases—AST and ALT—among patients with baseline elevations (>30 U/L) in these enzymes. "Because elevated transaminase levels are associated with impaired glucose homeostasis, the objective of this analysis was to test the hypothesis that changes in ALT and AST in responders would be associated with changes in glucose parameters and adiponectin," stated Dr. Mamputu.
Study authors pooled data from two Phase 3 studies of tesamorelin evaluated in HIV+ patients with excess abdominal fat. Patients who had a ≥8% reduction in VAT were considered treatment responders. Multivariable linear regression was used to calculate changes in AST/ALT. Spearman's correlations were carried out to assess the association between changes in liver transaminases and changes in glucose parameters and adiponectin.
The data indicated that a change in ALT had a significant positive correlation with changes in fasting blood glucose (r=0.15; P<0.025) and HbA1c (r=0.14; P=0.036) in tesamorelin responders who received treatment for 26 weeks. Among responders who were hepatitis B or C negative, a change in ALT had a positive correlation with changes in fasting blood glucose (r=0.17; P=0.018) with a trend towards association with changes in fasting insulin (r=0.14; P=0.06) and HbA1c (r=0.13; P=0.08).
Moreover, tesamorelin responders who received treatment for 52 weeks showed that change in ALT trended to a positive association with changes in fasting blood glucose (r=0.21; P=0.09), fasting insulin (r=0.21; P=0.08), and HOMA-IR (r=0.22; P=0.08). Change in ALT, however, trended towards a negative association with changes in adiponectin (–0.22, P=0.09). Among patients negative for hepatitis B or C, change in ALT was positively correlated with changes in fasting insulin (r=0.36; P<0.001) and HOMA-IR (r=0.33; P=0.02).
At Week 52, changes in AST had a positive correlation to changes in fasting glucose (r=0.27; P=0.048) and adiponectin (r=–0.28; P=0.049).
Excess VAT was associated with liver fat in HIV-infected patient taking antiretroviral therapy. Dr. Mamputu concluded, "Strategies aimed at reducing VAT and liver fat may help preserve glucose homeostasis in HIV-infected patients." Findings from the study showing the association between liver transaminases and glucose parameters "may account for the preservation of glucose homeostasis seen in these patients."
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