Arash Rahimi, Mahdie Kalhor, Rosa Azad, Amir Mohammad Karami, Aydin Hassanpour Adeh, Fatemeh Eslampanah, Yasamin Moeinipour, Aida Bakhshi, Samira Peiravi, Mahdyieh Naziri, Niloofar Deravi
Endocrinology Research and Practice - 2026;30(1):55-63
Objective: Data on the effects of melatonin on insulin sensitivity and resistance is limited and controversial. This meta-analysis aims to investigate the impact of melatonin on insulin resistance and insulin sensitivity. Methods: Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, and Google Scholar databases up to March 29, 2025. Randomized controlled trials (RCTs) evaluating melatonin's effects on glucose metabolism parameters were included. Data extraction and quality assessment were performed using Joanna Briggs Institute (JBI) checklists. Statistical analyses utilized random-effects models to account for heterogeneity. Results: Eleven RCTs involving 393 participants were analyzed. Pooled estimates showed no significant effect of melatonin on insulin resistance (homeostatic model assessment for insulin resistance: weighted mean difference (HOMA-IR: WMD) = -0.15, 95% CI: -0.50 to 0.19, P = .38). Insulin sensitivity outcomes demonstrated a non-significant reduction (WMD = -0.51, 95% CI: -0.81 to -0.21, P = .89). Substantial heterogeneity was observed (I2 = 85.4%), attributed to variability in melatonin dosing (1-40 mg/day), intervention durations (acute to 24 weeks), and participant characteristics (healthy vs. type 2 diabetes mellitus). Conclusion: Melatonin supplementation did not significantly improve insulin resistance and showed a non-significant trend toward reduced insulin sensitivity, particularly at higher doses. High heterogeneity underscores the need for cautious interpretation and individualized clinical application. Future large-scale RCTs should prioritize subgroup analyses by dose, administration timing, and baseline metabolic status to clarify melatonin's role in glucose regulation.
