The first step
The insulin-sparing effect of metformin and its positive effect on glucose metabolism is now well documented in insulin-treated type 2 diabetic patients, although the mechanisms of these effects are not overly clear (1). In insulin-treated type 1 diabetic patients, the use of metformin has only been assessed in a few studies and, surprisingly, the same insulin-sparing effect has been found despite some methodological difficulties. However, the clinical interest of metformin in the treatment of type 1 diabetes has remained questionable. For the first time, we have shown in a randomized double-blind trial that metformin has an insulin-sparing effect in type 1 diabetic patients (even if the studied population was not clinically insulin resistant) (2).
The selected patients were C-peptide negative after intravenous glucagon injection and were not identified as having metabolic syndrome. The patients were moderately overweight (BMI close to 25 kg/m2), and their daily insulin needs were not greater than that seen for other type 1 diabetic patients. The insulin-sparing effect of metformin was obtained for basal insulin needs but not for prandial needs. Although no definitive explanation could be given, it is now clear that the use of metformin may be appropriate for some type 1 diabetic patients.
Our study was designed to assess the insulin-sparing effect of metformin in insulin-treated type 1 diabetic patients, and this end was achieved. However, it was not designed to give clinical or biological criteria of indications associated with metformin use and insulin. We found that a subset of patients had a reduction of at least 20% in insulin requirements with stable and satisfactory glucose control, but a backward logistic regression did not allow prediction criteria of a good response to be defined. Thus, an expanded study using selection criteria identified in our previous study coupled with a larger range of BMI or bodyweight and a larger range of daily insulin doses in selected patients must be performed to determine therapeutic indications of this association
We believe that metformin use could be beneficial in type 1 diabetic patients who are overweight or obese, are receiving large doses of insulin, and have an HbA1c >8%. The use of metformin could be very useful in these patients but must be carried out under clinical and biological supervision to avoid complications such as lactic acidosis, which remains exceptional in our experience of type 1 and in type 2 diabetic patients.
Address correspondence to Laurent Meyer, Service de Diabétologie, Maladies Métaboliques & Maladies de la Nutrition, CIC-INSERM, Hôpital Jeanne d’Arc, Centre Hospitalo-Universitaire de Nancy, B.P. 303, 54201 Toul Cedex, France. E-mail:.
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