Metformin
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| 1,1-dimethyl-biguanide | |
| CAS number 657-24-9 | ATC code A10BA02 |
| Chemical formula | C4H11N5 |
| Molecular weight | 129.166 |
| Bioavailability | ? |
| Metabolism | ? |
| Elimination half-life | ? |
| Excretion | ? |
| Pregnancy category | ? |
| Legal status | ? |
| Routes of administration | ? |
Metformin (Glucophage®) is an anti-diabetic drug from the biguanide class (its other members are the withdrawn agents phenformin and buformin).
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Uses
The main use for metformin is for the treatment of diabetes mellitus, especially when is concomitant obesity and insulin resistance. It is also being used increasingly in polycystic ovary syndrome (PCOS) and non-alcoholic steatohepatitis, two other diseases that feature insulin resistance.
Mode of action
Despite its therapeutic benefits, the actual mode of action of metformin is uncertain. A report from 2001 (Zhou G et al) indicated that it acts by activating AMP-activated protein kinase (AMPK) in liver cells, leading to increased fatty acid oxidation and glucose uptake by cells and decreased lipogenesis and hepatic glucose production. Its net effect in an improvement in insulin resistance.
Side-effects
The most common side effect of Metformin HCl immediate-release is diarrhea. In a clinical trial of 286 subjects, 53.2% of the 141 who were given Metformin IR (as opposed to placebo) reported diarrhea, and 25.5% reported nausea/vomiting. (source: Drug Facts & Comparisons 2005)
Phenformin was withdrawn because of an increased risk of lactic acidosis (up to 60 cases per million patient-years). In recent studies it was revealed that, as long as it is not prescribed to patients who are at risk, metformin is much safer, and the risk of lactic acidosis approximates that of people who are not on the medication (Salpeter SR et al).
Contra-indications
Metformin should not be used in any condition that may increase the risk of lactic acidosis. This includes heart failure, kidney disorders (creatinine over 150 μmol/l), lung disease and liver disease.
History
The class of biguanide originates from the French lilac (Galega officinalis), a plant known for several centuries to improve the symptoms of diabetes mellitus.
Sources
- Witters LA. The blooming of the French lilac. J Clin Invest 2001;108:1105-1107. DOI 10.1172/JCI200114178 (http://dx.doi.org/10.1172/JCI200114178).
- Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Arch Intern Med 2003;163:2594-602. PMID 14638559.
- Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 2001;108:1167-1174. DOI 10.1172/JCI200113505 (http://dx.doi.org/10.1172/JCI200113505).it:Metformina