Metformin and sleep disorders.

Metformin is a widely used anti-diabetic drug. Deterioration of sleep is an important unwanted side effect of metformin. Here, the authors review and present the details on metformin and sleep problem.

INTRODUCTION

Diabetes mellitus is a common endocrine disorder. Millions of patients have to use anti-diabetic drugs. A widely used oral anti-diabetic drug is metformin (C4H11N5 · HCl). Under fasting conditions, about 50 % bioavailability of metformin has been observed.[1] After ingestion, metformin is slowly absorbed and reaches its peak level in blood in 1-3 hours, and its elimination half-life is about 1.5-6 hours.[1] The main route of metformin elimination is tubular secretion.[1] Metformin use results in decreased hepatic glucose production and decreased intestinal absorption of glucose.[1] In addition, metformin can help improve insulin sensitivity via increasing peripheral glucose uptake and utilization.[1]

Similar to other drugs, adverse effects of metformin are reported. These can result in poor compliance of the diabetic patient,[1] causing an irregular intake of the drug.[1] Apart from the well known ill effects of hypoglycemia and diarrhea, other unwanted effects of metformin have also been observed. The effect of metformin on sleep is interesting. Here, the authors review and present the details on metformin and sleep problem.

METFORMIN – INDUCED INSOMNIA

Metformin – induced insomnia is widely mentioned in old and obese diabetic patients who have been diagnosed with diabetes mellitus recently and prescribed with metformin. The development of insomnia can be seen within a few days after starting metformin. This is an interesting unwanted effect that is not quoted in other antidiabetic drugs. In a web report (www.eheathme.com), about 1.4% of people who observed side-effects when taking metformin had insomnia.[2] There are some arguments whether metformin is the causative substance leading to insomnia. Diabetic patients are normally prone to insomnia.[3] Blood glucose levels are related to the duration of sleep , and change in blood glucose levels after starting with metformin might be a possible mechanism by which metformin induces insomnia.[4] In addition, the co-morbidity, diabetes mellitus with depression is a common condition, and this too can result in insomnia.[5] The defect of the endocannabinoid system, which is a drug target, in diabetes mellitus can be a possible pathogenesis of metformin-induced insomnia.[6]

METFORMIN AND DREAMS

As already discussed, metformin can result in sleep disturbance, and this might affect normal dream patterns. Nightmares are reported in patients receiving metformin.[7] However, they are less frequent than insomnia.[8] Indeed, the cerebral blood glucose is known for its relationship to dreaming[910] and the change of its level after intake of metformin might be the underlying pathogenesis of nightmares.

METFORMIN AND SLEEP APNEA

There are many reports on relationship between diabetes and sleep apnea. In contrast, metformin is proven for its preventive ability for sleep apnea.[1112] Since metformin is useful for management of diabetes cases with metabolic syndrome, which is a risk factor for sleep apnea,[1314] hence, metformin is helpful for preventing sleep apnea. In animal model studies, it is reported that “Metformin is an efficient curative and preventive treatment for sleep apnea, suggesting that insulin resistance modifies the ventilatory drive independently of obesity.”[11]

METFORMIN AND SLEEPWALKING

This topic is little mentioned. Although this problem is extremely rare, it has been reported.[15] Nevertheless, there is no proposed pathological mechanism of sleepwalking in a patient receiving metformin. However, in a hyperthyroid patient, there is a report on the sleepwalking due to the defect in the endocrine pathway.[16]

CONCLUSION

There are many reports that metformin can result in some sleep problems, especially insomnia. On the other hand, metformin is proven to be useful for preventing sleep apnea. The exact relationship between metformin and sleep problems is still not clear, and further studies for a more clear understanding are warranted.