Melatonin supplements have become a common sleep aid and are generally considered safe, but questions remain about how they may affect the metabolic health of people with certain genetic risk factors.

New research led by Jingyi Qian, PhD, Richa Saxena, PhD, and Frank A.J.L. Scheer, PhD, of Mass General Brigham and the Broad Institute of MIT and Harvard, investigated whether melatonin impairs glucose tolerance in carriers of a common MTNR1B gene variant linked to increased risk of type 2 diabetes and the underlying mechanisms.

The researchers enrolled 21 healthy adults, including 10 carriers of the risk variant and 11 noncarriers, in a randomized, double-blind, crossover trial. Each participant received a single 5 mg oral dose of melatonin and a placebo on separate, nonconsecutive days during a tightly controlled five-day laboratory protocol. The regulation of blood sugar was evaluated with the frequently sampled intravenous glucose tolerance test (FSIGT) combined with insulin infusion and modeling.

Overall, the researchers found that melatonin significantly worsened glucose tolerance in MTNR1B risk-variant carriers, but not in noncarriers. The effects appeared to stem from two key mechanisms:

● Melatonin reduced the pancreas’ initial insulin response to rising blood sugar levels. 

● Melatonin interfered with the feedback mechanisms that normally help slow insulin secretion once enough has been released, which may lead to impairment of pancreatic function in the long run. 

Given the widespread use of over-the-counter melatonin supplements and the high prevalence of the MTNR1B risk variant (affecting about half of the general population), the authors say their findings support more personalized guidance on melatonin use, including the timing of supplementation relative to meals and an individual’s genetic makeup.

Published in Diabetes Care on June 25, 2026 | Read the paper: “Melatonin Impairs Glucose Tolerance, First-Phase Insulin Secretion, and Insulin Feedback Inhibition; Interaction With MTNR1B Diabetes Risk Variant”

Summary reviewed by: Jingyi Qian, PhD, lead author; Frank Scheer, PhD, co-senior author