Metformin lactacidosis

No significant difference was seen in the calculated mortality risk for metformin-associated lactacidosis and glibenclamide-associated hypoglycaemia. Sulphonylureas were no less dangerous than metformin and both should be used with care in non-insulin-dependent diabetics, especially in elderly subjects and those with impaired renal or hepatic function (Campbell, 1985). 

Phenformin is a hypoglycaemic (better to say antihyperglycaemic) agent that was formerly used in the treatment of NIDDM. It is associated with an unacceptably high incidence of lactacidosis that has often proved fatal. Metformin is still on the market in Canada and Europe, but the sul-phonylureas comprise the only class of oral agents that are commercially available for the treatment of Type-II diabetes in the United States. 

Acute poisoning with metformin calls for intensive supportive therapy. Lactacidosis may require treatment with sodium bicarbonate or furosemide, a combination of insulin and glucose or peritoneal dialysis or haemodialysis (Lalau et al., 1989). 

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... 

Kidney failure requires special attention because of metformin accumulation. Severe lactacidotic coma despite normal renal function has been reported in a 35-year-old diabetic man taking metformin and alcohol (Ryder, 1984). While fasting plasma lactate concentrations remained unaltered after metformin, a rise was noted in response to meals (from 1.4 0.1 to 1.8 0.2 mM) (Pedersen et al., 1989). Arterial blood gas analysis in one case revealed a pH of 6.76 and a bicarbonate level of 1.6 mM before treatment of lactacidosis. After therapy, which included oxygen, volume expansion and haemodialysis, the patient completely recovered (Gan et al., 1992). 

In order to avoid lactacidosis, it is important to select patients correctly and to ensure that contraindications such as renal involvement, advanced age and chronic alcoholism are observed before treatment with metformin (Lebech and Olesen, 1990). The role of lactic acid in the triggering of panic attacks has been discussed (Gin et al., 1989b). 

The risk of lactate accumulation should be appreciated in patients with renal insufficiency, liver dysfunction and after acute illness with hypoxia, when therapy should be stopped. Although metformin is often bracketed with phenformin in the context of lactacidosis, different pharmacodynamics and adherence to prescribing guidelines render such a comparison unwarranted (Bailey and Nattrass, 1988). 

The mortality risk for hypoglycaemia caused by sulphonylureas is not significantly different from lactacidosis associated with metformin (Campbell, 1984). 

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