The Effects of Ramelteon on Glucose Metabolism and Sleep Quality in Type 2 Diabetic Patients With Insomnia: A Pilot Prospective Randomized Controlled Trial.
BACKGROUND
Insomnia is associated with the onset and development of diabetes. Melatonin affects sleep quality and glucose metabolism in diabetic patients with insomnia. We administered ramelteon, an agonist of melatonin, to type 2 diabetic patients and investigated its effects on glucose metabolism and insomnia.


METHODS
This multicenter, prospective, randomized, and observational pilot study was performed between April 2014 and April 2015 at three institutes in Japan. Patients were prescribed ramelteon 8 mg/day for 3 months (first period). And patients were divided at random into the continuation group that continued taking ramelteon and the discontinuation group that discontinued taking ramelteon for 3 additional months (second period). The primary endpoint was change in glycated hemoglobin (HbA1c) level. Secondary endpoints were changes in global Pittsburgh sleep questionnaire index (PSQI) score and other glucose metabolism makers.


RESULTS
We enrolled 42 patients, and 32 patients completed the first period. Their mean HbA1c was 6.7%, and global PSQI score was 8.1 on average. HbA1c level did not change but global PSQI score improved from 8.1 to 7.2 by ramelteon (P = 0.030). Thirty-one patients completed the second period. HbA1c level did not change in the continuation group, but it increased from 6.7% to 6.9% (P = 0.003) in the discontinuation group. Global PSQI score did not change in each group. There was no rebound insomnia.


CONCLUSIONS
Treatment with ramelteon did not change the HbA1c level but improved sleep quality in type 2 diabetic patients with insomnia. Discontinuation of ramelteon slightly increased the HbA1c level and did not worsen sleep quality.
Division of Metabolism and Endocrinology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Associations, Yokohama, Japan; Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Tetsuji
T
Tsunoda
Division of Metabolism and Endocrinology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Associations, Yokohama, Japan.
Masayo
M
Yamada
Division of Metabolism and Endocrinology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Associations, Yokohama, Japan.
Tomoaki
T
Akiyama
Division of Metabolism and Endocrinology, Department of Internal Medicine, Yokohama Sakae Kyosai Hospital, Federation of National Public Service Personnel Mutual Associations, Yokohama, Japan.
Taichi
T
Minami
Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Taishi
T
Yoshii
Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan; Department of Endocrinology and Metabolism, Chigasaki Municipal Hospital, Chigasaki, Japan.
Yoshinobu
Y
Kondo
Department of Endocrinology and Metabolism, Chigasaki Municipal Hospital, Chigasaki, Japan.
Shinobu
S
Satoh
Department of Endocrinology and Metabolism, Graduate School of Medicine, Yokohama City University, Yokohama, Japan.
Yasuo
Y
Terauchi
Insomnia ramelteon; Pittsburgh sleep questionnaire index; Short form 36; Type 2 diabetes mellitus