Metformin as an adjunct to entecavir therapy does not accelerate hepatitis B surface antigen (HBsAg) clearance in patients with hepatitis B e antigen (HBeAG)-negative chronic hepatitis B virus (HBV) infection, according to study findings published in Annals of Hepatology.
Researchers in China conducted a double-blind, single-center, randomized, placebo-controlled trial between January 2020 and September 2020 to evaluate the effects of adjunctive metformin in patients with chronic HBV who were receiving entecavir for more than 12 months. Patients were randomly assigned in a 1:1 fashion to receive either adjunctive metformin (n=29) or placebo (n=31) for 24 weeks. The primary outcome was serum HBsAg levels at weeks 24 and 36.
Among patients in the metformin and placebo groups, the mean (SD) age was 49.4 (6.3) and 50.5 (7.7) years, 82.8% and 83.9% were men, and the median serum HBsAg level (log IU/mL) at baseline was 2.43 (IQR, 1.64-2.73) and 2.47 (IQR, 1.64-2.76), respectively.
At week 24, adjusted mean serum HBsAg levels did not significantly differ between patients in the metformin (2.18; 95% CI, 2.12-2.24) and placebo (2.13; 95% CI, 2.07-2.19) groups. Further analysis of adjusted mean serum HBsAg levels at week 36 showed similar results among patients in the metformin (2.17; 95% CI, 2.11-2.23) and placebo (2.11; 95% CI, 2.05-2.17) groups.
Although a higher rate of adverse events (AEs) was observed among patients in the metformin group, it was not significantly different vs those in the placebo group (31.0% vs 16.1%; P =.227). The most common AEs included diarrhea (10.3% vs 6.5%), abdominal distension (6.9% vs 0%), and HBeAg seroreversion (10.3% vs 6.5%). No severe AEs were reported in either patient group.
Results of sensitivity analyses also showed no significant differences in serum HBsAg levels at week 24 or 36 between patients in the metformin and placebo groups.
Study limitations include the small sample size, the single-center setting, and limited generalizability. In addition, the 24-week course of adjunctive metformin may have been insufficient in regard to serum HBsAg clearance.
According to the researchers, “these findings raise the question of why those impactful antiviral and immunomodulatory effects of metformin do not translate into a clinical benefit.”
Disclosure: One author declared receipt of a grant from the Innovative Research Group Project of the National Natural Science Foundation of China, which supported this study.
Zhang W, Li YY, Shang QH, et al. Randomised controlled trial: effect of metformin add-on therapy on functional cure in entecavir-treated patients with chronic hepatitis B. Ann Hepatol. 2022;27(6):100745. doi:10.1016/j.aohep.2022.100745