The Effect of Hesperidin and Diosmin Individually or in Combination on Metabolic Profile and Neuropathy among Diabetic Patients with Metabolic Syndrome: A Randomized Controlled Trial

Current evidence supports the association of metabolic syndrome (MetS) with neuropathy. Limited data are available on proper strategies to control metabolic disorders and neuropathy among patients with type2 diabetes mellitus (T2DM). We aimed to determine hesperidin and diosmin efficacy individually and in combination among T2DM patients with neuropathy and meet MetS criteria. In this parallel-group designed trial, 129 T2DM patients with MetS and neuropathy were recruited and randomized to receive their oral hypoglycemics with either hesperidin (1g/day), or diosmin (1g/day), or combination of both or oral hypoglycemics without intervention for 12 weeks. Diabetic neuropathy was evaluated using Michigan Neuropathy Screening Instrument (MNSI) at baseline and after trial. Anthropometric parameters, blood glucose and lipid profile were also assessed before and after the intervention using paired student t-test within groups. The trial is registered at clinicaltrials.gov as NCT05243238. By completion of the trial duration, both hesperidin and diosmin groups showed significant reduction in blood glucose, triglycerides (TGs) and low density lipoprotein (LDL) from baseline (p<0.05). However, the magnitude of improvement in metabolic components significantly increased with hesperidin and diosmin combination. Although MNSI scores improved significantly in both groups, the reduction was more significant with the combination of hesperidin and diosmin. Moreover, the change in MNSI score was significantly correlated with the improvement in metabolic profile components including LDL, TGs and fasting blood glucose. Oral supplementation of hesperidin and diosmin was associated with improvement in metabolic syndrome and diabetic neuropathy and the combination of both was superior in efficacy.