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Metformin for Type 2 Diabetes Patients

Metformin is an oral biguanide antihyperglycemic agent prescribed to patients suffering from type 2 diabetes mellitus (non-insulin-dependent diabetes mellitus), which rates among the first-line medications across the globe and can be used both as a monotherapy or combined with several other drugs used for treating diabetes. The medication can also assist in treating metabolic and reproductive problems associated with polycystic ovary syndrome (Inzucchi, Lipska, Mayo, Bailey, & McGuire, 2014).

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As far as its pharmacodynamics is concerned, the agent is capable of lowering hepatic glucose production as well as its absorption while increasing insulin-mediated glucose uptake (Schernthaner et al., 2013). Metformin activates a liver enzyme AMPK (AMP-activated protein kinase) and increases its activity affecting glucose production and metabolism. It allows metformin to improve glycemic control of the body decreasing basal and postprandial plasma glucose (Inzucchi et al., 2015). The consumption of the drug may lead to weight loss in diabetes patients suffering from obesity.

Monotherapy does not bring about hypoglycemia or hyperinsulinemia since it does not affect the secretion of insulin (which makes its pharmacokinetics different from that of similar drugs); however, combination with insulin may produce hypoglycemic effects. Side effects, which include dyspepsia, nausea, unpleasant metallic taste, vomiting, abdominal bloating, and diarrhea, can be avoided through the use of smaller doses of the drug. The same measure is required in case of decreased renal function. When the drug is administered in combination with sulfonylureas, it is important to watch for such symptoms as abdominal pain, hunger, increase anxiety, weakness, tremor, and sweating (Pawlyk, Giacomini, McKeon, Shuldiner, & Florez, 2014).

The agent is administered orally and has an oral bioavailability of 50-60% under the condition that it is not consumed with meals as such administration may delay absorption through minimizing possible adverse reactions. Some researchers claim that the absorption of metformin does not depend on its dosage. On the contrary, an inverse relationship between the dose and the time of absorption has been hypothesized suggesting a saturable process of absorption (Santoro et al., 2016). However, the data that could allow making conclusions are limited. The complete absorption of metformin happens within six hours. The drug is subjected to renal excretion 6-8 hours after consumption (the period may be longer in patients suffering from renal problems) (Bolinder et al., 2014).

The peak concentration in plasma is supposed to be reached approximately 3 hours after the administration of the drug. However, the information about the relationship of its concentration in plasma and metabolic effects is rather insufficient: in the state of fasting, the levels may vary from 0.5 to 1.0 mg/L whereas after a meal they may increase up to 1.0-2.0 mg/L (Schernthaner et al., 2013). No particular figures can be obtained (as they vary from one patient to another), which implies that monitoring does not have real value. However, it is highly important to identify the concentration of the drug in plasma in case lactic acidosis is suspected as it is one of the few criteria that allow concluding whether the condition was caused by the agent (Goswami et al., 2014). If metformin is detected, forced diuresis or hemodialysis are required to eliminate it from the organism. All these consequences can be prevented if the patient follows the guidelines and contraindications (Inzucchi et al., 2015).

Metformin is not metabolized by the organism: research in patients shows that the drug is excreted unaltered in the urine with not metabolites identified. Almost 90% of metformin is eliminated in 24 hours in patients that do not have any complications (Santoro et al., 2016).

References

Bolinder, J., Ljunggren, Ö., Johansson, L., Wilding, J., Langkilde, A. M., Sjöström, C. D.,… Parikh, S. (2014). Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes, Obesity and Metabolism, 16(2), 159-169.

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Goswami, S., Yee, S. W., Stocker, S., Mosley, J. D., Kubo, M., Castro, R.,… Brett, C. (2014). Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin. Clinical Pharmacology & Therapeutics, 96(3), 370-379.

Inzucchi, S. E., Bergenstal, R. M., Buse, J. B., Diamant, M., Ferrannini, E., Nauck, M.,… Matthews, D. R. (2015). Management of hyperglycemia in type 2 diabetes, 2015: A patient-centered approach: Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care, 38(1), 140-149.

Inzucchi, S. E., Lipska, K. J., Mayo, H., Bailey, C. J., & McGuire, D. K. (2014). Metformin in patients with type 2 diabetes and kidney disease: A systematic review. Jama, 312(24), 2668-2675.

Pawlyk, A. C., Giacomini, K. M., McKeon, C., Shuldiner, A. R., & Florez, J. C. (2014). Metformin pharmacogenomics: Current status and future directions. Diabetes, 63(8), 2590-2599.

Santoro, A. B., Stage, T. B., Struchiner, C. J., Christensen, M. M. H., Brosen, K., & Suarez‐Kurtz, G. (2016). Limited sampling strategy for determining metformin area under the plasma concentration–time curve. British Journal of Clinical Pharmacology, 82(4), 1002-1010.

Schernthaner, G., Gross, J. L., Rosenstock, J., Guarisco, M., Fu, M., Yee, J.,… Meininger, G. (2013). Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea. Diabetes Care, 36(9), 2508-2515.

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StudyCorgi. (2020, December 3). Metformin for Type 2 Diabetes Patients. Retrieved from https://studycorgi.com/metformin-for-type-2-diabetes-patients/

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"Metformin for Type 2 Diabetes Patients." StudyCorgi, 3 Dec. 2020, studycorgi.com/metformin-for-type-2-diabetes-patients/.

1. StudyCorgi. "Metformin for Type 2 Diabetes Patients." December 3, 2020. https://studycorgi.com/metformin-for-type-2-diabetes-patients/.


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StudyCorgi. "Metformin for Type 2 Diabetes Patients." December 3, 2020. https://studycorgi.com/metformin-for-type-2-diabetes-patients/.

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StudyCorgi. 2020. "Metformin for Type 2 Diabetes Patients." December 3, 2020. https://studycorgi.com/metformin-for-type-2-diabetes-patients/.

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StudyCorgi. (2020) 'Metformin for Type 2 Diabetes Patients'. 3 December.

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