HormonesMelatonin

Melatonin impairs glucose tolerance and first-phase insulin secretion in MTNR1B diabetes risk variant carriers

In a randomized, double-blind, placebo-controlled crossover trial, 5 mg oral melatonin worsened glucose tolerance (11.7% increase) and reduced early C-peptide responses (19.2% decrease) in MTNR1B G-allele risk carriers, but not in noncarriers. The impairments were driven by a 40% suppression of glucose-stimulated first-phase β-cell responsivity and dysregulated insulin negative feedback.

Last updated: Jul 8, 2026•1 RCTs•📖 Read as article →

Evidence Score

Evidence Score44/100
Human RCT★★☆☆☆
Meta-analysis☆☆☆☆☆
Mechanism★★★★★
Safety★★★★☆
Confidencelow

Study Evidence

Study 1. Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant.

observational

Qian J, Stefanovski D, Andersen PAK, Vujovic N, Kelly L, Lepson J, Nguyen H, Byrne S, Wang W, Mandrup-Poulsen T, Adler G, Garaulet M, Saxena R, Scheer FAJL · Diabetes care (2026)

Participants: N/A
Duration: 5-day laboratory protocol per participant
Intervention: 5 mg oral melatonin vs. placebo
Outcome: Glucose tolerance, first-phase β-cell responsivity, C-peptide responses, insulin-induced decline in second-phase insulin secretion rate, hypoglycemia events
Effect Size: First-phase β-cell responsivity suppression: 40% (95% CI -52.4 to -24.3, Padj = 0.0003)
Population: 21 healthy participants of European ancestry (10 MTNR1B risk carriers, 11 noncarriers)

Result:

PubMed: 42346809DOI: 10.2337/dc26-0164

Mechanism Graph

Melatonin binds to MTNR1B receptors on pancreatic β-cells
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Suppresses glucose-stimulated first-phase insulin secretion
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Slows insulin-induced decline in second-phase insulin secretion rate
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Results in worsened glucose tolerance and impaired glycemic control

Limitations

  • ⚠Small sample size (n=21) limits generalizability
  • ⚠Single dose (5 mg) and short-term exposure may not reflect long-term melatonin use

Frequently Asked Questions

Does melatonin affect blood sugar in everyone?▼

No, the study found that melatonin impaired glucose tolerance only in individuals carrying the MTNR1B diabetes risk variant (G-allele), not in noncarriers.

What dose of melatonin was used in this study?▼

Participants received 5 mg of oral melatonin, which is a common over-the-counter dose.

How was glucose tolerance measured in this trial?▼

Glycemic dynamics were assessed using insulin-modified intravenous glucose tolerance tests with minimal-model analysis.

What is the MTNR1B gene variant?▼

The MTNR1B gene encodes the melatonin receptor 1B; a common variant (G-allele) increases the risk of type 2 diabetes and may make carriers more susceptible to melatonin's adverse metabolic effects.

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References

  1. 1.Qian J, Stefanovski D, Andersen PAK, Vujovic N, Kelly L, Lepson J, Nguyen H, Byrne S, Wang W, Mandrup-Poulsen T, Adler G, Garaulet M, Saxena R, Scheer FAJL. "Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant.." Diabetes care, 2026. PMID: 42346809 DOI: 10.2337/dc26-0164
Disclaimer: This content is for educational purposes only and is not medical advice. Evidence scores reflect the quality and quantity of available research, not clinical recommendations. Always consult a healthcare professional before starting any supplement or intervention.