Adjuvant potential of metformin with standard anti-seizure medications in persons with active epilepsy: a randomised controlled trial

The purpose of this study was to investigate the efficacy and safety of add-on metformin treatment in persons with active epilepsy (a-PWE). This is a single-centric, double-blind, placebo-controlled trial randomised a-PWE (1:1) to receive either metformin (extended-release 500 mg) or matching placebo for 6 months along with background antiseizure medications. Primary outcome was percentage change in seizure frequency/month, and secondary outcomes were 50% responder rate, serum mTOR expression, and serum total antioxidant capacity (TAC), body composition analysis, quality of life (QOL), and safety assessment. Among the randomised a-PWE (n = 60, 30 in each group), no significant difference in percentage change in seizure frequency/month [median (IQR), 5.00 (- 11.25 to 23.45) vs. 0 (- 15.00 to 25.00), median difference (95% CI), 0 (- 18.75 to 12.50), p = 0.687], mTOR expression, TAC, and QOL was noted between metformin and placebo. Compared to baseline, QOL was significantly improved (p = 0.019) in metformin group, but this was not evident in placebo. Body composition analysis revealed a significant increase in percentage-change in BMI (p