Life Neuroscience

Metformin, the most commonly prescribed therapy for type 2 diabetes, has been scrutinized as  emerging for sleep modulation. Metformin might affect sleep-wake patterns partly through the regulation of metabolic pathways, including glucose metabolism and AMP-activated protein kinase (AMPK) activity, the latter of which is involved in circadian rhythm regulation. Several studies suggested that metformin might have positive effects on improving sleep quality by imposing blood glucose control and decreasing nocturnal hypoglycemia emergence; however, some observed an association between sleep problems such as insomnia or fragmented sleep and metformin possibly related to either gastrointestinal upset or alterations in energy metabolism. The data from animal and human studies describing the effects of metformin on sleep architecture have been inconsistent. Metformin has been associated with increased slow-wave sleep in rodent models, hinting at its potential as a sleep restorative agent. However, human studies are conflicting, with some patients reportedly experiencing longer and deeper sleep after glycemic control is improved, while others experience sleep disturbances as a side effect. These differences could be attributed to the variability of drug tolerance among individuals, other comorbid diseases, or differences in dosage and should be highlighted for future studies. Altogether, the association between metformin and sleep is complex and intricate. Although presumably, its metabolic actions might indirectly contribute to improved sleep in people with diabetes, it is less clear if it has a direct effect on sleep physiology, which needs to be validated in more well-controlled studies. Future studies should also involve the long-term effects, dose-dependent influence, and interactions with other drugs to determine the role of metformin for sleep health and optimize metformin use among patients with sleep-related metabolic disorders.