Metformin
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- Decreases Gluconeogensis
- Increases perpheral utliisation of glucose
Contents |
Introduction
Of all drugs used to treat type 2 diabetes it has by far the best outcome data in terms of mortality and if drug treatment is indicated must be regarded as the monotherapy drug of first choice. In type 2 diabetes with heart failure, which is quite common, it is the only drug to decrease mortality out of sulphonylureas, glitazones or insulin. It is better than sulphonylureas in reducing mortality[1][2] and both insulin and sulphonylureas in reducing malignancy[3]. It may not be so good as other choices in patients with ischaemic heart disease[4] but the evidence is inconclusive[5].
Clinical Use
Indications
In type 2 diabetes and with insulin in type 1 diabetes.
Administration
Oral
Clinical Issues
Contra-indications
- Not in MODY
- Renal failure
Cautions and Interactions
It can induce Vitamin B12 deficiency and this is correctable as long as detected.
Side effects
- Anorexia
- Weight loss
- Lactic acidosis (delayed licensing in USA until outcome data started to become overwhelming to its favour)
Special advice
Very rarely causes lactic acidosis, usually where severe heart failure or renal failure co-exist with diabetes. Older strictures on its use, including those of NICE are illogical in specifying a creatinine level below which it should not be used, or at least ostentatiously reviewed since this may correspond to very varying levels of renal function in different people. With the introduction of arithmetic into clinical medicine it is now practical to regard glomerular filtration rate (GFR) as the proper indicator. Subject to caveats about the accuracy of EGFR an estimated GFR (EGFR) of 30 ml/min #check if per 1.7m^2 or raw# is a more logical boundary[6].
The best thing to do may be to continue treatment below this level, but the decision should be carefully taken and documented and involve a consensus between nephrologist, diabetologist and the patient's other doctors.
Pharmacology
There is a suggestion that it might enhance CD8 memory T cell function and so act on immune memory which might for example extend the usefulness of polysaccharide vaccines[7]. Metformin augments AMP kinase and female mice models are consistent with increased lifespan as a result.
References
- ↑ Simpson SH, Majumdar SR, Tsuyuki RT, Eurich DT, Johnson JA. Dose-response relation between sulfonylurea drugs and mortality in type 2 diabetes mellitus: a population-based cohort study. CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2006 Jan 17; 174(2):169-74.(Link to article – subscription may be required.)
- ↑ Evans JM, Ogston SA, Emslie-Smith A, Morris AD. Risk of mortality and adverse cardiovascular outcomes in type 2 diabetes: a comparison of patients treated with sulfonylureas and metformin. Diabetologia. 2006 May; 49(5):930-6.(Link to article – subscription may be required.)
- ↑ Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes care. 2006 Feb; 29(2):254-8.
- ↑ Fisman EZ, Tenenbaum A, Benderly M, Goldbourt U, Behar S, Motro M. Antihyperglycemic treatment in diabetics with coronary disease: increased metformin-associated mortality over a 5-year follow-up. Cardiology. 1999; 91(3):195-202.
- ↑ Belcher G, Lambert C, Goh KL, Edwards G, Valbuena M. Cardiovascular effects of treatment of type 2 diabetes with pioglitazone, metformin and gliclazide. International journal of clinical practice. 2004 Sep; 58(9):833-7.
- ↑ http://www.clinicalanswers.nhs.uk/index.cfm?question=3917
- ↑ Pearce EL, Walsh MC, Cejas1 PJ, Harms GM, Shen H, Wang L, Jones RG, Choi Y. Enhancing CD8 T-cell memory by modulating fatty acid metabolism. Nature doi:10.1038/nature08100 3 June 2009
