Metformin side effects

Oral formulations of metformin are rapidly and completely absorbed. The agent is poorly bound to plasma proteins its duration of action is determined exclusively by renal elimination. Higher concentrations of metformin than in most tissues are found in the intestinal mucosa, giving tise to common side effects (irritation, diarrhoea etc.). 

Primary side effects associated with metformin therapy are gastrointestinal in nature, including decreased appetite, nausea, and diarrhea. These side effects can be minimized through slow titration of the dose and often subside within 2 weeks. Discontinuation because of side effects occurs in only 3% to 5% of patients. 

Avandia (rosiglitazone) as with other thiazolidinediones is used either as monotherapy or in combination with either metformin or a sulphonylurea. A disadvantage of rosiglitazone is the risk of heart failure as a side-effect. This risk is increased when rosiglitazone is used in patients with cardiovascular disease and when used in combination with insulin. Blood-glucose control may deteriorate temporarily when a thiazolidinedione is substituted for an oral antidiabetic agent. 

Individualize dosage on the basis of efficacy and tolerance, while not exceeding the maximum recommended daily dose of metformin IR 2,550 mg in adults and 2,000 mg in children (10 to 16 years of age) the maximum recommended daily dose of metformin ER in adults is 2,000 mg (2,500 mg with Fortamet). Give metformin IR in divided doses with meals and give metformin ER once daily with the evening meal. Start at a low dose, with gradual dose escalation, to reduce Gl side effects and... 

The drug metformin is useful in the treatment of patients with type 2 diabetes mellitus who are obese and whose hyperglycemia cannot be controlled by other agents. There are reports that some patients are predisposed to the toxic side effects of this drug, which include potentially fatal lactic acidosis. 

Two relatively new formulations of metformin are available. Glucovance is a combination of metformin and glyburide that may be helpful for diabetics who require both a sulfonylurea and metformin, and Glu-cophage XR is an extended-release product of metformin that may be better tolerated in some patients who are prone to gastrointestinal side effects. Metformin is usually given two to three times a day at mealtimes. 

If metformin alone does not control the HbAlc, then metformin and a sulfonylurea should be given. A thiazolidinedione can be substituted for either agent if unacceptable side effects occur, such as nausea or hypoglycaemia. A rapid-acting insulin secretagogue may be added for people with erratic lifestyles, as it can be given once daily. 

Mechanism uncertain. Metformin does not undergo hepatic metabolism. Renal tubular secretion is the major route of metformin elimination. Aminoglycosides are also principally excreted via the kidney, and nephrotoxicity is an important side-effect Watch and monitor for hypoglycaemia, and warn patients about it - For signs and symptoms of hypoglycaemia, see Clinical Features of Some Adverse Drug Interactions, Hypoglycaemia... 

Metformin is mainly absorbed in the upper part of the GI tract with high tendency to adsorb to the intestinal epithelium owing to its ionized nature at physiological pH, and thus its absorption patterns are affected (mainly paracellular), and it causes remarkable GI side effect. This fact, together with the finding that metformin active sites are mainly found in the GI tract and the liver, makes metformin a good candidate for GRDF.f" The blood concentrations of metformin... 

This side effect is rare, but dangerous and serious (Misbin, 1977 Korbonen et al., 1979). Lactacidosis, which is fatal in 50% of cases, occurs less with metformin than with phenformin (Cavallo-Perin et al., 1989), usually in patients whose condition contraindicated the use of metformin in the first place. There may be the possibility of a process of adaptation on prolonged... 

Metformin used as monotherapy reduced plasma glucose levels in normal-weight Type-II diabetics considerably (172 to 103 mg per 100 ml), whereas serum insulin was unchanged over a 3 month period (Jackson et al., 1987). The hypoglycaemic action of metformin became fully effective within 2-3 weeks of treatment. Clinical studies point out that gastrointestinal side effects can be avoided if medication is started slowly and taken postprandially (Fig. 25). 

Acute side effects of metformin, which occur in up to 20% of patients, include diarrhea, abdominal discomfort, nausea, metallic taste, and anorexia. These usually can be minimized by increasing the dosage of the drug slowly and taking it with meals. Intestinal absorption of vitamin B12 and folate often is decreased during chronic metformin therapy, and calcium supplements reverse the effect of metformin on vitamin B12 absorption. 

Acute side effects of metformin occur in up to 20% ofpcdients and include diarrhea, abdominal discomfort, nausea, metallic taste, and anorexia. These usually can be minimized by increasing... 

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