Efficacy and safety of prolonged-release melatonin in insomnia patients with diabetes: a randomized, double-blind, crossover study

Abstract

Background

Diabetes is a major comorbidity in insomnia patients. The efficacy and safety of prolonged-release melatonin 2 mg in the treatment of glucose, lipid metabolism, and sleep was studied in 36 type 2 diabetic patients with insomnia (11 men, 25 women, age 46–77 years).

Methods

In a randomized, double-blind, crossover study, the subjects were treated for 3 weeks (period 1) with prolonged-release melatonin or placebo, followed by a one-week washout period, and then crossed over for another 3 weeks (period 2) of treatment with the other preparation. All tablets were taken 2 hours before bedtime for a period of 3 weeks. In an extension period of 5 months, prolonged-release melatonin was given nightly to all patients in an open-label design. Sleep was objectively monitored in a subgroup of 22 patients using wrist actigraphy. Fasting glucose, fructosamine, insulin, C-peptide, triglycerides, total cholesterol, high-density and low-density lipoprotein cholesterol, and some antioxidants, as well as glycosylated hemoglobin (HbA1c) levels were measured at baseline and at the end of the study. All concomitant medications were continued throughout the study.

Results

No significant changes in serum glucose, fructosamine, insulin, C-peptide, antioxidant levels or blood chemistry were observed after 3 weeks of prolonged-release melatonin treatment. Sleep efficiency, wake time after sleep onset, and number of awakenings improved significantly with prolonged-release melatonin as compared with placebo. Following 5 months of prolonged-release melatonin treatment, mean HbA1c (±standard deviation) was significantly lower than at baseline (9.13% ± 1.55% versus 8.47% ± 1.67%, respectively, P = 0.005).

Conclusion

Short-term use of prolonged-release melatonin improves sleep maintenance in type 2 diabetic patients with insomnia without affecting glucose and lipid metabolism. Long-term prolonged-release melatonin administration has a beneficial effect on HbA1c, suggesting improved glycemic control.

Keywords:

• sleep
• insulin
• type 2 diabetes
• glucose
• melatonin

Disclosure

The study was an investigator-initiated trial and was funded by Neurim Pharmaceuticals Ltd. DG, MZ, and JW were the investigators and have no financial involvement with the company. ZM performed the laboratory assessments and has no financial connections with Neurim Pharmaceuticals Ltd. ML and NZ are employees of Neurim Pharmaceuticals Ltd.