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 < 0.001), fat % (p = 0.011), and fat mass (p = 0.004) in placebo compared to metformin. No significant safety concern was observed in metformin group, rather Liverpool adverse event profile (LAEP) score was significantly lower than placebo (p = 0.014). Significant improvement in lipid profile (triglycerides and high-density lipoprotein) and glycaemic parameters was observed in metformin group compared to baseline. Metformin intervention at the selected dose was not effective in terms of seizure reduction or modulation of mTOR expression compared to placebo. Further studies with higher dose with longer duration of intervention may be needed to establish the findings. Trial registration no. CTRI/2023/10/058825, date: 18.10.2023.