SAN FRANCISCO, CA—Treatment with extended-release naltrexone/bupropion (NB) for weight loss significantly improved and normalized serum alanine aminotransferase (ALT) levels in obese and overweight individuals at high risk for non-alcoholic fatty liver disease (NAFLD) with elevated liver enzymes, reported Allison Winokur, PhD, from Takeda Pharmaceuticals, Deerfield, IL, at The Liver Meeting® 2015.
“In this study, subjects potentially at the greatest risk, those with the highest ALT levels at baseline, demonstrated the largest reduction in ALT from baseline with NB-associated weight loss,” said Dr. Winokur.
NAFLD, a probable consequence of obesity, often presents with elevated ALT, but can improve with weight loss. Dr. Winokur and her team set out to examine the effect of extended release naltrexone/bupropion (NB), approved for obesity management, on ALT in non-diabetic, obese patients.
This post-hoc analysis pooled data from three Phase 3 trials for study participants who had received NB extended-release 32mg/360mg (n=781 NB responders) or placebo (n=663) for 56 weeks. NB patients had to lose at least 5% of their body weight at Week 16 to be included. Endpoints included changes from baseline (BL) for weight and ALT, proportion of patients achieving targeted 25% or 50% reductions in ALT, and proportion patients achieving Prati criteria for ALT (≤19 IU/L for women; ≤30 IU/L for men) at Week 56. Patients were divided into quartiles for analysis, based on baseline ALT values, Dr. Winokur said.
“Regardless of ALT quartile, subjects who received NB lost significantly more weight than subjects who received placebo” (P<0.001 for all comparisons), Dr. Winokur reported. “Weight loss for all quartiles was similar.”
Among NB responders, mean percentage-decreases in weight from baseline for quartiles 1, 2, 3 and 4 were: 13.0, 12.7, 12.9, and 11.0, she said. Patients treated with NB for 56 weeks experienced significantly greater weight loss vs. placebo (-12.4% vs. -2.7%, P<0.001).
“A positive linear correlation between weight loss and decreased ALT was observed in the NB group, which was most pronounced in the 4th quartile (r=0.396; P<0.001),” Dr. Winokur noted. “No differences in the frequency of adverse events were observed with NB between participants with and without elevated ALT.”
These results suggest that NB “should be further explored as a therapeutic option for overweight and obese patients with NAFLD,” Dr. Winokur concluded.