Effects of melatonin supplementation on diabetes: A systematic review and meta-analysis of randomized clinical trials

Background & aims: Melatonin appears as a supplement capable of helping with diabetes. However, there is no evidence from meta-analyses that showed significant results in insulin resistance and glycated hemoglobin. This study aimed to review the literature on randomized clinical trials that evaluated melatonin supplementation effects, compared to placebo, on diabetes parameters in humans. Methods: We conducted a systematic review and meta-analysis in the following databases: Pubmed, LILACS, Scielo, Scopus, Web of Science, Cochrane, and Embase. We included randomized clinical trials investigating melatonin supplementation's effects, compared to placebo, on fasting blood glucose, insulin resistance, and glycated hemoglobin. Non-randomized clinical trials, observation studies, and animal models were excluded. The Cochrane scale assessed the quality of the studies. We conducted a meta-analysis on fasting blood glucose, insulin resistance, and glycated hemoglobin. Results: Sixteen studies were included, of which 56% showed benefits from supplementation with melatonin in diabetes parameters compared with placebo. Our meta-analysis showed significant results for fasting blood glucose [mean difference: −4.65; 95% CI: −8.06, −1.23; p = < 0.01; I² = 58%], glycated hemoglobin [mean difference: −0.38; 95% CI: −0.67, −0.10; p = 0.30; I² = 18%], and insulin resistance [mean difference: −0.58; 95% CI: −1.00, −0.15; p = 0.17; I² = 35%]. Conclusions: Our results showed that melatonin supplementation was useful for reducing diabetes parameters when compared to placebo.