Effects of melatonin supplementation on blood glycemic indices in adults: a GRADE-assessed systematic review and dose-response meta-analysis of randomized controlled trials

INTRODUCTION: Melatonin, a neurohormone primarily known for its regulation of circadian rhythms, has recently received attention for its potential role in glucose metabolism. Several trials suggest that melatonin supplementation may influence glycemic control through mechanisms involving insulin sensitivity and oxidative stress. However, findings across studies remain inconsistent. This systematic review aimed to summarize current evidence on the effects of melatonin administration on blood glucose parameters in diverse adult populations. METHOD: PubMed, Web of Science, Scopus, and Google Scholar were searched for eligible randomized controlled trials (RCTs) published up to July 2025. Weighted mean differences (WMD) were calculated for net changes in risk factors using random effects models. RESULTS: 30 RCTs (with 31 arms) were included. melatonin supplementation significantly reduced fasting blood sugar (WMD = -2.66 mg/dl, 95%CI: -4.53 to -0.80, n = 27), insulin (WMD = -1.58 µIU/ml, 95%CI: -2.40 to -0.76, n = 16), HOMA-IR (WMD = -0.53, 95%CI: -0.85 to -0.20, n = 16), and improve Quantitative Insulin Sensitivity Check Index (QUICKI) (WMD = 0.01, 95%CI: 0.00 to 0.01, n = 7). No significant effects were observed on HbA1c (WMD = -0.45%, 95%CI: -0.94 to 0.04, n = 7). CONCLUSION: The results of the present meta-analysis showed that melatonin supplementation could significantly improve fasting blood glucose, insulin, and HOMA-IR levels. However, no significant results were observed for HbA1c. However, the results obtained were highly heterogeneous, so the results should be interpreted with caution.