| Item |
Information |
|
Drug Groups
|
approved |
|
Description
|
Metformin is a biguanide antihyperglycemic agent used for treating non-insulin-dependent diabetes mellitus (NIDDM). It improves glycemic control by decreasing hepatic glucose production, decreasing glucose absorption and increasing insulin-mediated glucose uptake. Metformin is the only oral antihyperglycemic agent that is not associated with weight gain. Metformin may induce weight loss and is the drug of choice for obese NIDDM patients. When used alone, metformin does not cause hypoglycemia; however, it may potentiate the hypoglycemic effects of sulfonylureas and insulin. Its main side effects are dyspepsia, nausea and diarrhea. Dose titration and/or use of smaller divided doses may decrease side effects. Metformin should be avoided in those with severely compromised renal function (creatinine clearance < 30 ml/min), acute/decompensated heart failure, severe liver disease and for 48 hours after the use of iodinated contrast dyes due to the risk of lactic acidosis. Lower doses should be used in the elderly and those with decreased renal function. Metformin decreases fasting plasma glucose, postprandial blood glucose and glycosolated hemoglobin (HbA1c) levels, which are reflective of the last 8-10 weeks of glucose control. Metformin may also have a positive effect on lipid levels. |
| Indication |
For use as an adjunct to diet and exercise in adult patients (18 years and older) with NIDDM. May also be used for the management of metabolic and reproductive abnormalities associated with polycystic ovary syndrome (PCOS). |
| Pharmacology |
Metformin is an oral antihyperglycemic agent that improves glucose tolerance in patients with NIDDM, lowering both basal and postprandial plasma glucose. Metformin is not chemically or pharmacologically related to any other class of oral antihyperglycemic agents. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with NIDDM or healthy subjects and does not cause hyperinsulinemia. Metformin does not affect insulin secretion. |
| Toxicity |
Acute oral toxicity (LD50): 350 mg/kg [Rabbit]. It would be expected that adverse reactions of a more intense character including epigastric discomfort, nausea, and vomiting followed by diarrhea, drowsiness, weakness, dizziness, malaise and headache might be seen. |
| Affected Organisms |
| • |
Humans and other mammals |
|
| Biotransformation |
Metformin is not metabolized. |
| Absorption |
Absorbed over 6 hours, bioavailability is 50 to 60% under fasting conditions. Administration with food decreases and delays absorption. Some evidence indicates that the level of absorption is not dose-related, suggesting that absorption occurs through a saturable process. Limited data from animal and human cell cultures indicate that absorption occurs through a passive, non-saturable process, possibly involving a paracellular route. Peak action occurs 3 hours after oral administration. |
| Half Life |
6.2 hours. Duration of action is 8-12 hours. |
| Protein Binding |
Metformin is negligibly bound to plasma proteins. |
| Elimination |
Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion. Approximately 90% of the drug is eliminated in 24 hours in those with healthy renal function. Renal clearance of metformin is approximately 3.5 times that of creatinine clearance, indicating the tubular secretion is the primary mode of metformin elimination. |
| Distribution |
654 L for metformin 850 mg administered as a single dose. The volume of distribution following IV administration is 63-276 L, likely due to less binding in the GI tract and/or different methods used to determine volume of distribution. |
| Clearance |
718-1552 mL/minute following single oral dose of 0.5-1.5 g. Metformin is removed by hemodialysis at a rate of approximately 170 ml/min under good hemodynamic conditions. |
| References |
| • |
Witters LA: The blooming of the French lilac. J Clin Invest. 2001 Oct;108(8):1105-7.
[Pubmed]
|
| • |
UNGAR G, FREEDMAN L, SHAPIRO SL: Pharmacological studies of a new oral hypoglycemic drug. Proc Soc Exp Biol Med. 1957 May;95(1):190-2.
[Pubmed]
|
| • |
Lord JM, Flight IH, Norman RJ: Metformin in polycystic ovary syndrome: systematic review and meta-analysis. BMJ. 2003 Oct 25;327(7421):951-3.
[Pubmed]
|
| • |
Marchesini G, Brizi M, Bianchi G, Tomassetti S, Zoli M, Melchionda N: Metformin in non-alcoholic steatohepatitis. Lancet. 2001 Sep 15;358(9285):893-4.
[Pubmed]
|
| • |
Nair S, Diehl AM, Wiseman M, Farr GH Jr, Perrillo RP: Metformin in the treatment of non-alcoholic steatohepatitis: a pilot open label trial. Aliment Pharmacol Ther. 2004 Jul 1;20(1):23-8.
[Pubmed]
|
|
| External Links |
|