Is this a good or bad idea?
The article by Meyer et al. (1) revives a debate regarding the appropriateness of metformin use for people with type 1 diabetes. Given the potential for coexisting lactic acidosis and diabetic ketoacidosis, how can one justify its use? Indeed, there was little reason to expect a benefit in patients who were studied: nonobese type 1 diabetic subjects with HbA1c <9.0% who were taking ∼0.7 units · kg insulin−1 · day−1. A modest average reduction of daily insulin requirements, 4.3 units, as compared with an increase of 1.7 units for placebo, does not seem to be worth the trade-off of increased risk for severe hypoglycemia (19 events in metformin group vs. 8 events in placebo group). There was no differential effect in terms of HbA1c. Only 7 of 31 patients (23%) treated with metformin responded in terms of a significant (20%) reduction in insulin requirement. Furthermore, it is likely that the incidence of hypoglycemia would be much greater if more aggressive metabolic targets of HbA1c had been applied. Despite the failure to observe diabetic ketoacidosis, the limited number and short period of observation does not permit the conclusion that metformin is safe in ketosis-prone diabetic subjects.
We have seen a number of type 1 diabetic patients who have received metformin prescriptions by other practitioners. It appears that these prescriptions were given because of a failure to identify latent autoimmune diabetes in adults or because the physician believed that the potential for insulin dose reduction and lipid improvement justified a putative small risk for diabetic ketoacidosis and lactic acidosis. The temptation to prescribe metformin is increased because of the high prevalence of metabolic syndrome among U.S. adults (2). Indeed, the diagnosis of metabolic syndrome can frequently be made in the type 1 diabetic population. For example, using BMI as a marker for metabolic syndrome, we observed an average BMI of 27 kg/m2 in 343 consecutive subjects with type 1 diabetes; this means that our average type 1 diabetic patient is overweight. A BMI ≥30 kg/m2, sufficient to diagnosis obesity, was observed in 89 of 343 subjects (26%). Seven of our type 1 diabetic patients had a BMI ≥41 kg/m2. Of these severely obese subjects, two were receiving metformin therapy as well as insulin.
The results of the study by Meyer et al. suggest that a small subset of type 1 diabetic patients benefit in terms of insulin dose reduction when metformin is added to insulin. Questions about long-term safety and efficacy in this patient population remain unanswered. Therefore, when is it reasonable and defensible to prescribe metformin in type 1 diabetes? We suggest that metformin should be avoided unless the following criteria are met: 1) insulin resistence is clearly interfering with satisfactory glucose control despite lifestyle interventions; 2) the risk of diabetic ketoacidosis is minimized by an intensive program of insulin, self-monitoring of blood glucose, urine ketone measurement if blood glucose exceeds 300 mg/dl, and regular medical supervision; 3) the patient receives counseling so that he or she understands the potential risk for lactic acidosis; and 4) efficacy is frequently evaluated to justify continued use of metformin.
Address correspondence to J. David Faichney, Center for Diabetes and Endocrinology, Saint Mary’s Mercy Medical Center, 300 Lafayette SE, Suite 2045, Grand Rapids, MI 49503. E-mail:.
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