Purpose: Type 2 diabetes mellitus (T2DM), often complicated by diabetic peripheral neuropathy (DPN), remains a leading global health burden. Despite advancements in pharmacotherapy, glycemic control is frequently suboptimal, prompting interest in adjunctive interventions. Selenium, a trace element with antioxidant and insulin-modulating properties, has been proposed as a potential therapeutic agent in T2DM management; however, evidence remains inconsistent, particularly in patients with DPN. To evaluate the effects of organic selenium supplementation on glycemic control, insulin resistance, quality of life, and sleep quality in individuals with T2DM and DPN. Methods: In this triple-blind, randomized, placebo-controlled clinical trial (ethics approval code: IR.TBZMED.REC.1401.374; trial registration number: IRCT20131009014957N10), 50 patients with T2DM and confirmed diabetic peripheral neuropathy (DPN) were randomized to receive either 200 μg/day of organic selenium (as selenium-enriched yeast) or placebo for 8 weeks. Primary outcomes included changes in fasting blood sugar (FBS), glycated hemoglobin (HbA1c), HOMA-IR, and QUICKI. Secondary outcomes encompassed quality of life (WHOQOL-BREF) and sleep quality (PSQI). Biochemical methods were used to measure laboratory biomarkers, and analysis was conducted using ANCOVA, adjusting for the baseline value of the outcome variable, baseline FBS, age, sex, BMI, and MNSI score. Results: Selenium supplementation significantly reduced FBS [adjusted mean difference (aMD) (95% CI): -33.95 mg/dL(- 64.2 to - 5.5); p=0.021], HbA1c [aMD (95% CI): -1.20% (- 1.79 to - 0.61); p<0.001], and HOMA-IR [aMD (95% CI): -1.57 (- 3.06 to - 0.08); p=0.039), while increasing QUICKI (aMD (95% CI): 0.02 (0.003 to 0.034); p=0.018), compared to placebo. Improvements in WHOQOL-BREF and sleep quality were observed within the selenium group but did not reach statistical significance in between-group analyses except for improving daytime dysfunction of sleep quality [aMD (95% CI): -0.54 (- 1.05 to - 0.03); p=0.039). Adverse events were minimal and comparable across groups. Conclusion: Eight weeks of organic selenium supplementation significantly improved glycemic indices and insulin sensitivity in patients with T2DM and DPN, without notable adverse effects. These findings suggest that selenium supplementation may serve as a potentially useful adjunctive intervention for improving short-term metabolic control in patients with T2DM and DPN. The approximately 1.2% reduction in HbA1c observed in this study may be clinically meaningful; however, the findings should be interpreted cautiously given the modest sample size, short follow-up duration, and single-centre design. Further long-term studies are warranted to elucidate its broader neuropsychological benefits.
