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

Abstract

Background: The study aimed to evaluate the association between sleep duration and insulin resistance (IR), compare the sensitivity of two IR indices (homeostatic model assessment for insulin resistance (HOMA-IR) vs. Matsuda Index), and investigate the causal impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on sleep traits through Mendelian randomization (MR).

Methods: We conducted a meta-analysis of randomized controlled trials and clinical studies (2014–2024) examining sleep duration’s effect on insulin sensitivity (IS), measured via HOMA-IR and Matsuda Index. Additionally, a two-sample MR analysis utilized single nucleotide polymorphisms (SNPs) related to GLP-1R expression and sleep traits (insomnia, short/long duration, chronotype) to assess the causal influence of GLP-1RA exposure on sleep characteristics.

Results: Meta-analysis revealed that reduced sleep duration was significantly associated with increased IR based on HOMA-IR, whereas the Matsuda Index, fasting blood glucose, and fasting insulin showed inconsistent associations. Promoting sleep extension may improve HOMA-IR readings. The MR analysis indicated a causal relationship between genetically proxied GLP-1RA exposure and changes in sleep: specifically, reduced total sleep time and an earlier sleep phase.

Conclusions: Sleep duration is a key modifiable determinant of IR, with HOMA-IR demonstrating greater sensitivity to sleep-related IS changes. Moreover, GLP-1RA may modify sleep architecture—shortening sleep duration and advancing sleep timing—which could offset some therapeutic effects on IR. These findings support integrating sleep management into personalized treatment strategies for individuals with IR.