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

Clin Endocrinol (Oxf). 2021 Nov;95(5):691-701. doi: 10.1111/cen.14576. Epub 2021 Aug 18.

Abstract

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.

Keywords: HbA1c; glucose; insulin; insulin sensitivity; melatonin; meta-analysis; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Blood Glucose
  • Diabetes Mellitus, Type 2*
  • Fasting
  • Glucose
  • Glycated Hemoglobin / analysis
  • Humans
  • Insulin
  • Insulin Resistance*
  • Melatonin*

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Glucose
  • Melatonin