Effects of daily administration of melatonin before bedtime on fasting insulin, glucose and insulin sensitivity in healthy adults and patients with metabolic diseases. A systematic review and meta‐analysis

Background Melatonin is increasingly used as a pharmacological sleep aid but it is also emerging as a regulator of glucose homoeostasis. Yet, previous research has been ambiguous with reports of both positive and negative effects of melatonin on glucose metabolism. Objectives To assess the effect of daily treatment with melatonin on fasting glucose, insulin, insulin sensitivity and haemoglobin A1c (HbA1c) levels. Data Sources MEDLINE, EMBASE, CENTRAL, clinicaltrials.gov and clinicaltrialsregister.eu were systematically searched. Eligibility Criteria, Participants and Interventions All randomized, placebo‐controlled studies with melatonin treatment were assessed. We included studies with daily melatonin treatment (≥2 weeks) of healthy adults or patients with metabolic diseases. Methods Hedges' g differences were calculated for the metabolic parameters of the included studies, heterogeneity was assessed with χ2 and I2 tests and meta‐analyses were performed with the random‐effects model. Results Long‐term treatment with melatonin did not change fasting glucose significantly compared with placebo (g: −0.07 [−0.22 to 0.08], n = 603) but it reduced fasting insulin levels slightly (g: −0.27 [−0.50 to −0.04], n = 278) and trended towards reduced insulin resistance (HOMA‐IR) (g: −0.20 [−0.44 to 0.03], n = 278). HbA1c levels were largely unaffected by melatonin treatment compared with placebo (g: 0.14 [−0.19 to 0.46], n = 142). Conclusions With the available literature, melatonin seems to be a glucose‐metabolic safe sleep aid in patients with metabolic diseases and in healthy adults. It may even have beneficial glucose‐metabolic effects as fasting insulin levels were reduced in this meta‐analysis, but the confidence intervals of the meta‐analyses are wide, underscoring the need for further research within this field.