Metformin (Efficacy)

Metformin is an oral antidiabetic drug commonly used in the treatment and prevention of type 2 diabetes. Despite being a highly effective drug, in some people, hyperglycemia progresses and these patients need an adjustment in therapy.

Metformin is used alone or in combination with other medications, including insulin, to treat type 2 diabetes (a condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood). Metformin belongs to a class of oral hypoglycaemic drugs called biguanides. Metformin helps control the amount of glucose (sugar) in your blood. It decreases the amount of glucose that is absorbed from food and the amount of glucose that the liver synthesizes. Metformin also increases the body's response to insulin, a natural substance that controls the amount of glucose in the blood. Metformin is not used to treat type 1 diabetes (a condition in which the body does not produce insulin and, therefore, cannot control the amount of sugar in the blood).

CONTRAINDICATIONS

Hypersensitivity diabetic ketoacidosis, diabetic precoma; acute pathology with risk of renal impairment: dehydration, severe infection, shock; acute or chronic disease with risk of tissue hypoxia: heart or respiratory failure, recent myocardial infarction, shock; acute alcohol intoxication, alcoholism.

Metformin is contraindicated in patients with renal or hepatic impairment.

Do not use metformin during pregnancy (if there’s a need to reduce blood glucose insulin should be used to maintain normal glucose levels).

CAUTIONS

Interrupt and hospitalize immediately before non-specific signs such as muscle cramps, digestive disorders, abdominal pain and severe asthenia.

Renal function should be monitored before initiating treatment, minimum monitoring of 1 time per year if renal function is normal and minimum 2-4 times per year if the creatinine level ≥ ULN (Upper Limit Normality) and in the elderly (in elderly patients also caution when starting concomitant treatment with antihypertensives, diuretics or NSAIDs for risk of renal deterioration).

The treatment should be discontinued 48 h before surgery with general, spinal or epidural anesthesia; resume after 48 hours or after resumption of oral nutrition, and only if renal function is normal.

Suspend treatment before or at the time of radiological examination with iodinated contrast medium (intravascular) and do not resume until after 48 h and only if renal function is normal.

If used in children, growth and puberty parameters should be monitored, especially in children between 10-12 years old.

Always in the treatment with metformin should be performed a close glycemic control and adjust the doses or change antidiabetic treatment depending on the results of clinical monitoring of the patient.

PHARMACOLOGIC INTERACTIONS

Exposure to metformin is increased by concomitant treatment with: cationic drugs eliminated by tubular secretion (eg cimetidine).

Glucocorticoids (systemic and local) and sympathomimetics can increase blood glucose (close monitoring should be carried out especially at the beginning and if necessary adjust the dose of metformin during concomitance and when discontinuing treatment with glucocorticoids or sympathomimetics).

The concomitance of metformin with diuretics (especially those of Henle loop) causes a risk of lactic acidosis.

Glucose levels can be reduced more than normal if metformin is taken together with ACE inhibitors (angiotensin-converting enzyme inhibitors) and the dose should be adjusted.

SIDE EFFECTS

Dysgeusia, nausea, vomiting, diarrhea, abdominal pain, loss of appetite, hypoglycaemia, extreme tiredness, weakness, malaise, vomiting, stomach pain, decreased appetite, deep and rapid breathing, shortness of breath, dizziness, fainting, abnormally slow or fast cardiac rhythm, reddening of the skin, muscle pain, cold sensation.

BRAND NAMES

  • Dianben®
  • Fortamet®
  • Glucophage®
  • Glumetza®
  • Riomet®

Genes analyzed

C11orf65 MTHFR SLC22A1

Bibliography

GoDARTS and UKPDS Diabetes Pharmacogenetics Study Group K, Wellcome Trust Case Control Consortium 2 C, Zhou K, Bellenguez C, Spencer CCA, Bennett AJ, et al. Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes. Nat Genet , 2011; 43(2):117–20.

van Leeuwen N, Nijpels G, Becker ML, Deshmukh H, Zhou K, Stricker BHC, et al. A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetes: a replication and meta-analysis of five cohorts. Diabetologia, 2012; 55(7):1971–7.

Jablonski KA, McAteer JB, de Bakker PIW, Franks PW, Pollin TI, Hanson RL, et al. Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes, 2010; 59(10):2672–81.

Florez JC. Pharmacogenetics in type 2 diabetes: precision medicine or discovery tool? Diabetologia, 2017; 60(5):800–7.

Jiménez-Ramírez FJ, Castro LM, Ortiz C, Concepción J, Renta JY, Morales-Borges RH, et al. Role of treatment-modifying MTHFR677C>T and 1298ª>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy. Drug Metab Pers Ther, 2017; 32(1):23–32.

Shu Y, Brown C, Castro R, Shi R, Lin E, Owen R, et al. Effect of Genetic Variation in the Organic Cation Transporter 1, OCT1, on Metformin Pharmacokinetics. Clin Pharmacol Ther, 2008;83(2):273–80.

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