Improvement of glycemic control by treatment for insomnia with suvorexant in type 2 diabetes mellitus

Norikazu Toi; Masaaki Inaba; Masafumi Kurajoh; Tomoaki Morioka; Noriyuki Hayashi; Tomoe Hirota; Daichi Miyaoka; Masanori Emoto; Shinsuke Yamada

doi:10.1016/j.jcte.2018.12.006

Improvement of glycemic control by treatment for insomnia with suvorexant in type 2 diabetes mellitus

J Clin Transl Endocrinol. 2018 Dec 18:15:37-44. doi: 10.1016/j.jcte.2018.12.006. eCollection 2019 Mar.

Authors

Norikazu Toi¹, Masaaki Inaba¹, Masafumi Kurajoh¹, Tomoaki Morioka¹, Noriyuki Hayashi¹, Tomoe Hirota¹, Daichi Miyaoka¹, Masanori Emoto¹, Shinsuke Yamada¹

Affiliation

¹ Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.

Abstract

Introduction: Acute and chronic insomnia can exacerbate type 2 diabetes mellitus (T2DM). We investigated suvorexant (an anti-insomnia drug that targets the orexin system) effects on sleep architecture and glucose metabolism in T2DM patients with insomnia.

Materials and methods: This 7 day open-label, single-arm, intervention trial included 18 subjects with T2DM and insomnia. After 1 day acclimatization, daily glucose levels, sleep architecture, and autonomic nervous function were evaluated by continuous glucose monitoring (CGM), single-channel electroencephalography, and accelerometry, respectively.

Results: Suvorexant treatment for 3 days significantly increased total sleep time and sleep efficiency, with partial suppression of sympathetic nerve activity. CGM-measured 24 h mean glucose level decreased significantly from 157.7 ± 22.9 to 152.3 ± 17.8 mg/dL, especially in the early glucose surge after the midnight nadir (from 28.3 ± 15.0 to 18.2 ± 9.9 mg/dL), and until supper with a significant improvement in homeostasis model assessment of insulin resistance from 4.0 ± 2.8 to 2.9 ± 1.6, respectively.

Conclusions: Suvorexant treatment for insomnia of subjects with T2DM significantly improved CGM-measured daily glycemic control, which was associated with changes in sympathomimetic tone and/or improved insulin sensitivity. The amelioration of insomnia may therefore be a target for improving glycemic control in T2DM patients with insomnia.

Keywords: AHI, Apnea–Hypopnea Index; AUC, area under the curve; Autonomic nervous function; BMI, body mass index; CGM, continuous glucose monitoring; CPR, C-peptide immunoreactivity; CVR-R, coefficient of variation of RR intervals; DSM-5, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition; Dawn phenomenon; EEG, electroencephalography; Glycemic control; HOMA-IR, homeostasis model assessment of insulin resistance; HR, heart rate; HRV, heart rate variability; HbA1c, glycated hemoglobin A1c; IQR, interquartile range; IRI, immunoreactive insulin; Insulin resistance; PSQI, Pittsburgh Sleep Quality Index; REM, rapid eye movement; SAS, Sleep Apnea Syndrome; SD, standard deviation; SDNN, standard deviation of the NN (i.e., R-R) intervals; T2DM, type 2 diabetes mellitus; Therapy for insomnia; Type 2 diabetes mellitus; bpm, beats per minute; eGFR, estimated glomerular filtration ratio.