Synopsis: The authors review the use of metformin therapy in patients with potential and sometimes strong contraindications for biguanide treatment.
Source: Sulkin TM, et al. Diabetes Care 1997;20:925-928.
The aim of Sulkin and colleagues was to determine the prevalence of conditions currently regarded as either contraindications or cautions to the use of metformin in patients with non-insulin dependent diabetes mellitus (NIDDM).
Of 89 consecutive patients whose notes could be evaluated in detail, only 41 (46%) had no contraindications or cautions to the use of metformin. Concomitant chronic disorders associated with a potentially increased risk of hyperlactatemia were renal impairment (n = 2; plasma creatinine concentrations of 1.7 and 2.3 mg/dL); cardiac failure (n = 2); and chronic liver disease (n = 2).
Other potentially relevant disorders included ischemic heart disease (n = 2), clinical proteinuria (n = 14), peripheral vascular disease (n = 22), and pulmonary disease (n = 7). Multiple conditions (i.e., 2, 3, or 4) were present in eight, five, and one patient, respectively.
The authors conclude that more than half of the patients in their series had concomitant conditions or complications conventionally regarded as cautions or contraindications to metformin. Ten percent of the patients had a multiplicity of such conditions. They point out that increased vigilance is required in these patients. Renal failure and major intercurrent illnesses may independently disturb lactate metabolism. Metformin should be withdrawn promptly under such circumstances.
COMMENT BY RALPH R. HALL, MD
Major drug studies eliminate many of the patients we routinely see in our practices because of their other complicating conditions. We, however, have to decide on what is the most practical treatment for these patients. This results in our managing patients with potential complications because there are few alternatives.
Metformin, because of differences in molecular structure and pharmacokinetics, has considerably less risk of inducing lactic acidosis than did phenformin, which was withdrawn because of this complication.1
The reported incidence of lactic acidosis is very low with metformin0.03 cases per 1000 patient years, with approximately 0.015 fatal cases per 1000 patient years.
The listed contraindications are serum creatinine of more than 1.5 mg/dL in males and more than 1.4 mg/dL in females. Acute elevation of creatinine can occur with shock and septicemia. Metformin should be held for 48 hours in patients undergoing radiological studies involving parenteral contrast material because these products may result in acute changes in renal function.
Obviously acute and chronic metabolic acidosis and known hypersensitivity are contraindications.
In my experience, many physicians are unaware that alcohol potentiates the effect of metformin on lactate metabolism; therefore, patients should be warned about excessive alcohol intake.
We should all remember that the University Group Diabetes Program demonstrated that oral drugs (tolbutamide and phenformin) resulted in an increase in cardiovascular deaths compared to those patients using insulin.2
References
1. Bailey CJ. Diabetes Care 1992;15:755-772.
2. University Group Diabetes Program. Diabetes 1970;19 (Suppl 2):789-830.
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