Journal of Endocrinology and Metabolism, ISSN 1923-2861 print, 1923-287X online, Open Access
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Original Article

Volume 16, Number 5, October 2026, pages 201-216

Sleep Duration and Insulin Resistance: Meta-Analysis Reveals Sleep Restriction Linked to Higher Insulin Resistance, and Mendelian Randomization Suggests Glucagon-Like Peptide-1 Receptor Agonist May Contribute to Sleep Modulation

Figures

↓  Figure 1. Search strategy illustrating the specific Medical Subject Headings (MeSH) terms included in the query. Logical operators OR and AND were used to refine the search. REM: rapid eye movement.
Figure 1.
↓  Figure 2. This colorful bias assessment table exhibits the judgments of researchers to included articles. The left list shows various kinds of bias. Green denotes low risk of bias, yellow unclear risk, and red high risk.
Figure 2.
↓  Figure 3. Study flow diagram illustrating the article screening process in this meta-analysis. The arrows indicate the progression through each step of inclusion and exclusion.
Figure 3.
↓  Figure 4. Directed acyclic graph (DAG) of the two-sample Mendelian randomization (MR) analysis examining the effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) phenotypes on various sleep patterns. The solid blue arrow marked with a red question mark represents the primary relationship explored in this study. Yellow blocks denote confounding variables, while yellow ellipses indicate unspecified external factors. Pink blocks along the pink arrow describe the traits of the selected SNPs. Blue blocks represent different included sleep behaviors. SNP: single nucleotide polymorphism; BMI: body mass index; short sleep: short sleep duration; long sleep: long sleep duration; chronotype: morning chronotype.
Figure 4.
↓  Figure 5. Forest plot illustrating the meta-analysis results on the effect of sleep restriction on insulin resistance, assessed by four different indicators: (a) Matsuda Index, (b) fasting blood insulin (FBI), (c) fasting blood glucose (FBG), and (d) homeostatic model assessment of insulin resistance (HOMA-IR). 95% CI: 95% confidence interval; SD: standard deviation; IV: inverse variance.
Figure 5.
↓  Figure 6. Forest plot illustrating the meta-analysis results of the effect of prolonged sleep duration on insulin resistance, assessed by the homeostatic model assessment for insulin resistance (HOMA-IR). 95% CI: 95% confidence interval; SD: standard deviation; IV: inverse variance.
Figure 6.
↓  Figure 7. Scatter plot depicting the results of a two-sample Mendelian randomization (MR) analysis, with glucagon-like peptide-1 receptor agonist (GLP-1RA) as the exposure phenotype and insomnia as the outcome phenotype. Insomnia was defined as difficulty initiating or maintaining sleep. Participants who responded “sometimes” or “usually” to the question, “Do you have trouble falling asleep at night or do you wake up in the middle of the night?” were classified as having insomnia.
Figure 7.
↓  Figure 8. Scatter plot illustrating the results of a two-sample Mendelian randomization (MR) analysis with glucagon-like peptide-1 receptor agonist (GLP-1RA) as the exposure phenotype and long sleep duration as the outcome phenotype. Long sleep duration is defined as self-reported habitual sleep of more than 9 h per night.
Figure 8.
↓  Figure 9. Scatter plot showing the results of a two-sample Mendelian randomization (MR) analysis with glucagon-like peptide-1 receptor agonist (GLP-1RA) as the exposure phenotype and short sleep duration as the outcome phenotype. Short sleep duration is defined as self-reported habitual sleep of less than 6 h per night.
Figure 9.
↓  Figure 10. Scatter plot illustrating the results of a two-sample Mendelian randomization (MR) analysis with glucagon-like peptide-1 receptor agonist (GLP-1RA) as the exposure phenotype and chronotype as the outcome phenotype. Chronotype was defined based on responses to two identical questions: “Are you naturally a night person or a morning person?” For this study, only participants identifying as “morning people” or “early birds” were classified as having a morning chronotype.
Figure 10.

Table

↓  Table 1. An Overview of the Key Characteristics of the Studies Incorporated in Our Meta-Analysis
 
ReferenceStudy designCountryParticipants ageParticipants BMIParticipants sexHabitual sleepSample sizeMain interventionExposure of variable of interestInsulin sensitivity
Participants sex shows the ratio of female to male. CPIR: cephalic phase insulin response; FBG: fasting blood glucose; FBI: fasting blood insulin; HOMA-IR: homeostatic model assessment for insulin resistance; IVGTT: intravenous glucose tolerance test; OGTT: oral glucose tolerance test; QUICKI: Quantitative Insulin Sensitivity Check Index; RCT: randomized controlled trial.
Eckel RH 2015 [19]RCTUK18 to 35 (22.4 ± 4.8)18.5–24.95:57–9.25 h16Sleep restrictionOGTT, IVGTTWorse
Sweeney EL 2021 [20]RCTUK18 to 40 (26 ± 5)24 ± 2.25:57–9 h12Sleep restrictionOGTTWorse
Sweeney EL 2020 [21]RCTUK25 ± 825.120:1Bedtime before 22:00 or after 1:00
Wake time before 6:00 or after 9:00		19Sleep restrictionOGTTWorse
Wang X 2016 [22]RCTUSA20.6 ± 1.324.5 ± 3.48:77.43 ± 0.64 h15Sleep restrictionOGTT, HOMA-IR, Matsuda Index, QUICKIWorse
Cedernaes J 2016 [23]RCTUK22.88 ± 0.6622.88 ± 0.450:17–9 h16Sleep restrictionOGTT, HOMA-IR, CPIRWorse
Hart CN 2015 [24]RCTUSA41.7 ± 10.331.0 ± 4.21:0Not available21Sleep restrictionHOMA-IRWorse
Rao MN 2014 [25]RCTUSA27 ± 524.1 ± 4.13:47.7 h14Sleep restrictionOGTT, CPIRWorse
Singh P 2023 [26]RCTUSA54 to 65 (59 ± 4)28.0 ± 2.61:0497 ± 11 min14Sleep restrictionFBI, FBG, HOMA-IRWorse
Tajiri E 2017 [27]RCTJapan21.6 ± 0.520.4 ± 2.01:06:16 ± 0:45 h16Sleep restrictionFBIWorse
Bener A 2020 [28]Cross-sectional StudyTurkey25 to 65Not available541:330Not available871Sleep restrictionHbA1c, FBGWorse
Shaw ND 2016 [29]RCTUSA11.3 to 14.1Not available1:1Habitual bedtime (21:00–22:30)
Morning (05:00–07:30)		14Sleep extensionFBI, FBGImproved
Chennaoui M 2016 [30]RCTUK31.4 ± 3.924.0 ± 2.00:16–9 h14Sleep extensionFBI, FBGImproved
Reutrakul, S 2022 [31]Pilot randomized trialUSA18 to 45 (42.0 ± 2.9)Not available1:0≤ 8 h14Sleep restrictionOGTT, HOMA-IRWorse
So-Ngern A 2019 [32]RCTThailand20 to 55 (33.6 ± 6.1)22.6 ± 3.219:3Not available21Sleep extensionFBI, FBG, HOMA-IR, Matsuda IndexImproved
Benedict C 2016 [33]Clinical TrailUSA23.3 ± 0.623.1 ± 0.60:1Not available16Sleep restrictionFBI, FBG, HOMA-IR, Matsuda IndexWorse
Souza JFT 2024 [34]RCTBrazil18 to 40 (26.2 ± 4.1)24.9 ± 3.10:17.4 ± 0.8 h28Sleep restrictionOGTT, HOMA-IRWorse
Zuraikat FM 2024 [35]RCTUSA20 to 75 (37.6 ± 13.9)25.5 ± 3.31:0457.7 ± 21.6 min38Sleep restrictionFBI, FBG, HOMA-IRWorse
Li X 2016 [36]Prospective Cohort StudyChina30 to 65 (51.0 ± 6.9)24.8 ± 3.22,736:3,109Not available5,845Sleep extensionHOMA-IR, FBGWorse
Widjaja NA 2023 [37]Observational StudyIndonesia13 to 18 (15.31 ± 1.39)33.68 ± 4.7481:397.07 ± 1.51 h120Sleep extensionHOMA-IR, FBG, FBIImproved