Metformin contraindications

Drug interactions metabolized by CYP450 3A4, may interact with drugs that inhibit or induce this enzyme May cause hypoglycemia in patients receiving insulin, sulfonylureas, or metformin contraindicated in pregnant women Limit vitamin A supplements... 

Under certain circumstances, and very rarely, the inhibition of gluconeogenesis by metformin may suppress lactic acid metabolism and precipitate a potentially fatal lactic acidosis. Impairment of renal function, liver disease, alcoholism, conditions that give rise to increased lactate production (e.g. congestive heart failure, infections) are therefore contraindications for the application of metformin. 

Metformin is contraindicated in patients with heart failure, renal disease, hypersensitivity to metformin, and acute or chronic metabolic acidosis, including ketoacidosis. The drug is also contraindicated in patients older than 80 years and during pregnancy (Pregnancy Category B) and lactation. 

The answer is b. (Katzung, pp 727—7282) Metformin is contraindicated in patients with type II diabetes in a number of instances, including... 

Metformin should be included in the therapy for all type 2 DM patients (if tolerated and not contraindicated) because it is the only oral antihypergly-cemic medication proven to reduce the risk of total mortality and cardiovascular death. 

Obese patients (>120% ideal body weight) without contraindications should be started on metformin initially, titrated to about 2,000 mg/day. A thiazolidinedione (rosiglitazone, pioglitazone) may be used in patients intolerant of or having a contraindication to metformin. 

Metformin is a biguanide used to treat diabetes mellitus. It is contraindicated in patients undergoing general anaesthesia since anaesthesia can interfere with renal function. The risk of lactic acidosis associated with metformin increases in patients with renal impairment. Metformin should be stopped before and during surgery where anaesthesia is indicated. Metformin should only be restarted after the renal function has returned to normal. 

Metformin, a biguanide derivative, can lower excessive blood glucose levels, provided that insulin is present Metformin does not stimulate insulin release. Glucose release from the liver is decreased, while peripheral uptake is enhanced. The danger of hypoglycemia apparently is not increased. Frequent adverse effects include anorexia, nausea, and diarrhea Overproduction of lactic acid (lactate acidosis, lethality 50%) is a rare, potentially fatal reactioa Metformin is used in combination with sulfony-lureas or by itself. It is contraindicated in renal insufficiency and should therefore be avoided in elderly patients. 

Renal impairment - Metformin is contraindicated in patients with renal impairment. Therefore, concomitant administration of rosiglitazone and metformin is contraindicated in these patients. However, no dosage adjustment is necessary when rosiglitazone is used as monotherapy in patients with renal impairment. 

Holstein A, Egberts EH. Traditional contraindications to the use of metformin - more harmful than beneficial . Dtsch Med Wochenschr 2006 131(3) 105-10 (in German). 

Adverse gastrointestinal symptoms (nausea, vomiting, anorexia, metallic taste, abdominal discomfort, and diarrhea) occur in up to 20% of individuals taking metformin this can be minimized by starting at a low dose and slowly titrating the dose upward with food. Like phenformin, metformin can cause lactic acidosis, but its occurrence is rare except when renal failure, hypoxemia, or severe congestive heart failure is present or when coadministered with alcohol. Metformin is also contraindicated in persons with hepatic dysfunction, but it appears to be safe for use in the hepatic steatosis that often occurs with fatty infiltration of the liver in poorly controlled type II diabetics. 

L A. Metformin causes lactic acidosis in patients with renal failure and severe congestive heart failure. It does not increase the risk of ketoacidosis and showed a reduction in cardiovascular comorbidities in a large study. It is contraindicated in patients with severe liver disease but does not cause hepatic necrosis. When used as monotherapy, metformin rarely causes hypoglycemia. 

Of 308 patients 73% had contraindications, risk factors, or intercurrent illnesses necessitating withdrawal of metformin (31) 19% had renal impairment, 25% heart failure, 6.5% respiratory insufficiency, and 1.3% hepatic impairment 51% had advanced coronary heart disease, 9.8% atrial fibrillation, 3.3% chronic alcohol abuse, 2% advanced peripheral arterial disease, and 0.7% were pregnant. 

In a retrospective study of 1874 patients with type 2 diabetes taking metformin, 25% had contraindications, including acute myocardial infarction, cardiac failure, renal impairment, and chronic liver disease (33). However, contraindications often did not lead to withdrawal of metformin in 621 episodes, only 10% stopped taking it. Only 25 and 18% stopped taking metformin when they developed renal impairment or myocardial infarction, respectively. One patient developed lactic acidosis, but this may have been a consequence of myocardial infarction. 

Contraindications to the use of metformin have been debated (34), in relation to the reduced number of cardiovascular events seen in the obese patients treated with metformin in the UK prospective diabetes study (UKPDS) (35). The authors stated inter alia that lactic acidosis is rare (1-5 cases per 100 000) and that in the absence of renal insufficiency accumulation of metformin is rare. Moreover, the authors of a Cochrane systematic review concluded that treatment with metformin was not associated with an increased risk of lactic acidosis (36). Tissue hypoxia is often the trigger for metformin accumulation. Many physicians do not comply with the official British contraindications. The author suggested the following necessary precautionary measures ... 

Others have stated that metformin is contraindicated when serum creatinine concentrations are over 133 pmol/1 (1.5 mg/dl) in men or 124 pmol/l (1.4 mg/dl) in women (15). 

Reconsideration of contraindications has also been proposed in a prospective study in patients with serum creatinine concentrations of 130-220 pmol/1 and coronary heart disease (n — 226), congestive heart failure (n = 94) and chronic obstructive pulmonary disease (n = 91). Half of the patients continued to take metformin and the other half stopped (39). Bodyweight and HbAic increased over 4 years in those who stopped taking metformin. Lactic acid concentrations were similar in the two groups. Deaths were similar in the two groups (62 and 64 respectively). The incidences of myocardial infarction, all cardiovascular events, and cardiovascular mortality were the same. Changes in additional therapy were only significant for insulin (30% versus 45% respectively) and diet (25% versus 0% respectively). 

All survived, but all needed hemodialysis. In all cases there were contraindications to metformin. 

In patients taking metformin, lactic acidosis is rare (3 per 100 000 patient-years) and is most often seen when contraindications to metformin (impaired kidney or liver function, alcoholism, circulatory problems, old age) are neglected or not detected (64). Although the relative risk of lactic acidosis with metformin is significantly lower than with phenformin or buformin (65), it has been repeatedly reported (SEDA-6, 371) (66), even in the absence of known contraindications (67). 

All patients admitted to a hospital during 6 months who had taken at least one dose of metformin were retrospectively evaluated for susceptibility factors for metformin-associated lactic acidosis (8). There were 263 hospitalizations in 204 patients. In 71 admissions there was at least one contraindication, such as renal or liver disease, renal dysfunction, congestive cardiac failure, metabolic acidosis, or an intravenous iodinated contrast medium given within 48 hours of metformin. In 29 (41%) metformin was continued despite the contraindication. The most frequent contraindication was a raised serum creatinine, but in only eight of the 32 admissions was metformin withdrawn. Of nine patients using metformin who died (not necessarily directly related to metformin), six had an absolute contraindication. In two patients who died and in one who survived, blood lactate was increased and this was temporally related to the use of metformin. 

Sulkin TV, Bosnian D, Krentz AJ. Contraindications to metformin therapy in patients with NIDDM. Diabetes Care 1997 20(6) 925-8. 

Holstein A, Nahrwold D, Hinze S, Egberts EH. Contraindications to metformin therapy are largely disregarded. Diabet Med 1999 16(8) 692-6. 

Rachmani R, Slavachevski I, Levi Z, Zadok B-S, Kedar Y, Ravid M. Metformin in patients with type 2 diabetes mellitus reconsideration of traditional contraindications. Eur J Int Med 2002 13 428-33. 

The combination of metformin + thiazolidinediones (glitazones) is contraindicated or not recommended in patients taking therapy for cardiac failure. In a retrospective study of 12 505 and 13 158 patients with cardiac failure and diabetes in two different years (1998/9 and 2000/1)... 

Pioglitazone, is indicated once daily in patients not controlled by metformin alone. It is contraindicated by cardiac or hepatic failure. Weight gain and oedema are the main adverse effects. 

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