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Table of Contents
Year : 2012  |  Volume : 16  |  Issue : 7  |  Page : 63-64

Metformin and sleep disorders

Wiwanitkit House, Bangkhae, Bangkok, Thailand

Date of Web Publication24-Mar-2012

Correspondence Address:
Somsri Wiwanitkit
Wiwanitkit House, Bangkhae, Bangkok 10160
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/2230-8210.94262

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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.

Keywords: Metformin, sleep disorders, side effect

How to cite this article:
Wiwanitkit S, Wiwanitkit V. Metformin and sleep disorders. Indian J Endocr Metab 2012;16, Suppl S1:63-4

How to cite this URL:
Wiwanitkit S, Wiwanitkit V. Metformin and sleep disorders. Indian J Endocr Metab [serial online] 2012 [cited 2021 May 11];16, Suppl S1:63-4. Available from: https://www.ijem.in/text.asp?2012/16/7/63/94262

   Introduction Top

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 (C 4 H 11 N 5 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 Top

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 Top

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 [9],[10] and the change of its level after intake of metformin might be the underlying pathogenesis of nightmares.

   Metformin and Sleep Apnea Top

There are many reports on relationship between diabetes and sleep apnea. In contrast, metformin is proven for its preventive ability for sleep apnea. [11],[12] Since metformin is useful for management of diabetes cases with metabolic syndrome, which is a risk factor for sleep apnea, [13],[14] 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 Top

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 Top

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.

   References Top

1.Bouchoucha M, Uzzan B, Cohen R. Metformin and digestive disorders. Diabetes Metab 2011;37:90-6.  Back to cited text no. 1
2.Metformin and insomnia. Available from: http://www.ehealthme.com/ds/metformin/insomnia+concerns. [Last accessed on 2011 Jun 1].  Back to cited text no. 2
3.Rosekind MR, Gregory KB. Insomnia risks and costs: Health, safety, and quality of life. Am J Manag Care 2010;16:617-26.  Back to cited text no. 3
4.Nakajima H, Kaneita Y, Yokoyama E, Harano S, Tamaki T, Ibuka E, et al. Association between sleep duration and hemoglobin A1c level. Sleep Med 2008;9:745-52.   Back to cited text no. 4
5.Goodnick PJ. Use of antidepressants in treatment of comorbid diabetes mellitus and depression as well as in diabetic neuropathy. Ann Clin Psychiatry 2001;13:31-41.  Back to cited text no. 5
6.Scheen AJ. The endocannabinoid system: A promising target for the management of type 2 diabetes. Curr Protein Pept Sci 2009;10:56-74.  Back to cited text no. 6
7.Avery JK. A therapeutic nightmare. Tenn Med 2000;93:415-6.  Back to cited text no. 7
8.Nightmare. Available from: http://www.ehealthme.com/sa/3105465/nightmare. [Last accessed on 2011 Jun 1].  Back to cited text no. 8
9.Gottschalk LA, Buchsbaum MS, Gillin JC, Wu J, Reynolds CA, Herrera DB. Positron-emission tomographic studies of the relationship of cerebral glucose metabolism and the magnitude of anxiety and hostility experienced during dreaming and waking. J Neuropsychiatry Clin Neurosci 1991;3:131-42.  Back to cited text no. 9
10.Heiss WD, Pawlik G, Herholz K, Wagner R, Wienhard K. Regional cerebral glucose metabolism in man during wakefulness, sleep, and dreaming. Brain Res 1985;327:362-6.  Back to cited text no. 10
11.Ramadan W, Dewasmes G, Petitjean M, Wiernsperger N, Delanaud S, Geloen A, et al. Sleep apnea is induced by a high-fat diet and reversed and prevented by metformin in non-obese rats. Obesity (Silver Spring) 2007;15:1409-18.  Back to cited text no. 11
12.Ramadan W, Petitjean M, Loos N, Geloen A, Vardon G, Delanaud S, et al. Effect of high-fat diet and metformin treatment on ventilation and sleep apnea in non-obese rats. Respir Physiol Neurobiol 2006;150:52-65.  Back to cited text no. 12
13.Martin-Du Pan RC, Ruiz J. Metabolic syndrome: Jumble syndrome of obesity or specific entity? Which treatment: Diet or Polypill? Rev Med Suisse 2008;4:366-73.  Back to cited text no. 13
14.Aylwin S, Al-Zaman Y. Emerging concepts in the medical and surgical treatment of obesity. Front Horm Res 2008;36:229-59.   Back to cited text no. 14
15.Sleepwalking. Available from: http://www.ehealthme.com/ds/metformin/sleep+walking. [Last accessed on 2011 Jun 1].  Back to cited text no. 15
16.Ajlouni KM, Ahmad AT, El-Zaheri MM, Ammari FL, Jarrah NS, Abujbara MA, et al. Sleepwalking associated with hyperthyroidism. Endocr Pract 2005;11:5-10.  Back to cited text no. 16

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