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. 2017 Jul 18:9:187-198.
doi: 10.2147/NSS.S130505. eCollection 2017.

Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients

Orfeu M Buxton  1   2   3   4 , Milena K Pavlova  1   5 , Shawn P O'Connor  1 , Wei Wang  1   2 , John W Winkelman  1   6
Affiliations

Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients

Orfeu M Buxton et al. Nat Sci Sleep. .

Abstract

Study objectives: Primary insomnia (PI) may increase diabetes risk. We tested the hypothesis that the effects of PI on glucose metabolism could be improved by 2 months of pharmacological treatment.

Methods: Adult men and women meeting clinical criteria for PI were studied (n=20, body mass index 25.1±2.7 kg/m2, age 39.7±7.9) in a randomized, double-blind, placebo-controlled clinical trial. The study consisted of two 1-day inpatient admissions to a General Clinical Research Center separated by 2 months of at-home treatment with 3 mg eszopiclone or placebo. During inpatient admissions, each subject underwent two intravenous glucose tolerance tests (IVGTTs) pre- and post-treatment. Diet was controlled for micro- and macro-nutrient content and calories on the day prior to pre- and post-treatment IVGTTs. Subjects were randomized following completion of the initial IVGTT to take either placebo or eszopiclone 30 min prior to bedtime at home for 2 months.

Results: Two-month eszopiclone treatment did not change insulin sensitivity, glucose tolerance, or any of the sleep measures significantly, compared with placebo. Changes in glycated hemoglobin (HbA1c, clinical measure of glycemic control) were correlated with changes in diary-reported total sleep time in the eszopiclone group (r=0.66, p=0.0360), and in the combined groups' data (r=0.55, p=0.0125). Changes in polysomnography-measured wake after sleep onset, a hallmark of PI, were positively related to changes in IVGTT-derived glucose effectiveness, or non-insulin-mediated glucose uptake.

Conclusion: Treatment with 3 mg eszopiclone for 2 months, compared with placebo, did not significantly influence either sleep or measures of diabetes risk in this preliminary study.

Keywords: IVGTT; diabetes; eszopiclone; insulin sensitivity; metabolism; primary insomnia; sleep duration; wake after sleep onset.

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Conflict of interest statement

Disclosure Although this investigator-initiated study was sponsored in part by Sunovion Pharmaceuticals Inc. (formerly Sepracor), the authors analyzed the data and wrote the paper. OMB has received two investigator-initiated grants from Sepracor Inc. (now Sunovion; ESRC-0004 and ESRC-0977, ClinicalTrials.gov Identifiers NCT00555750, NCT00900159), and two investigator-initiated grants from Cephalon Inc. (now Teva; ClinicalTrials.gov Identifier: NCT00895570). OMB received Speaker’s Bureau, CME and non-CME lecture honoraria and an unrestricted educational grant from Takeda Pharmaceuticals, North America. OMB served as a consultant and expert witness for Dinsmore LLC, and received consulting fees for serving on the Scientific Advisory Board of Matsutani America and from the Wake Forest University Medical Center (NC). OMB received speaking fees and/or travel support for speaking from Chevron; American Academy of Craniofacial Pain; National Heart, Lung, and Blood Institute; National Institute of Diabetes and Digestive and Kidney Diseases; National Postdoctoral Association; Oklahoma State University; Oregon Health Sciences University; SUNY Downstate Medical Center; American Diabetes Association; and New York University. JWW has participated in research sponsored by Glaxo SmithKline, UCB Pharma, and Impax Pharmaceuticals. He has been a consultant for Impax Pharmaceuticals and UCB Pharma, and part of the scientific advisory board for Zeo Inc. The other authors report no conflict of interests in this work.

Figures

Figure 1
Figure 1
Protocol schema. Abbreviation: IVGTT, intravenous glucose tolerance test; PSG, polysomnography; q 30, every 30 minutes.
Figure 2
Figure 2
Glucose metabolism in chronic primary insomnia patients (n=20). Notes: (A) and (B) Mean glucose levels (±SE) during IVGTT at baseline (black lines) and following 2 months of at-home treatment in chronic primary insomnia patients receiving placebo (A; red line) or eszopiclone (B; green line). Left arrow, glucose infusion at time t=0 min; right arrow, insulin infusion at time t=20 min. (C) and (D): Mean insulin levels (±SE) during the first phase of the insulin response to the IVGTT. (E–G): IVGTT parameters were calculated using the Minmod Millennium 2000 software. (E): AIRg (first phase); (F): Disposition index; (G): Insulin sensitivity. There were no significant effects of drug administration on these metabolic indices. Abbreviations: AIRg, acute insulin response to glucose; IVGTT, intravenous glucose tolerance test; n.s., not significant; SE, standard error; SI, insulin sensitivity.
Figure 3
Figure 3
Changes in sleep related to metabolic measures. Notes: (A): Changes post-Tx in sleep diary-derived TST (min) were significantly correlated with change (post-Tx baseline) in glycated hemoglobin, a measure of glycemic control in which a decrease reflects lower diabetes risk. (B) Changes post-Tx relative to baseline in PSG-derived WASO (min), a hallmark of sleep discontinuity in primary insomnia, were significantly correlated with the IVGTT measure of glucose effectiveness (min−1), a measure of non-insulin dependent glucose utilization. Abbreviations: IVGTT, intravenous glucose tolerance tests; post-Tx, post-treatment; PSG, polysomnography; TST, total sleep time; WASO, wake after sleep onset.
See this image and copyright information in PMC

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