Metformin and Insulin in Type 1 Diabetes: The first step

doi:10.2337/diacare.26.5.1655-a

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Letters: Comments and Responses
Letter

Metformin and Insulin in Type 1 Diabetes

The first step

Laurent Meyer, MD and Bruno Guerci, MD, PHD

From the Service de Diabétologie, Maladies Métaboliques & Maladies de la Nutrition, CIC-INSERM, Hôpital Jeanne d’Arc, Centre Hospitalo-Universitaire de Nancy, Toul Cedex, France

The insulin-sparing effect of metformin and its positive effecton glucose metabolism is now well documented in insulin-treatedtype 2 diabetic patients, although the mechanisms of these effectsare not overly clear (1). In insulin-treated type 1 diabeticpatients, the use of metformin has only been assessed in a fewstudies and, surprisingly, the same insulin-sparing effect hasbeen found despite some methodological difficulties. However,the clinical interest of metformin in the treatment of type1 diabetes has remained questionable. For the first time, wehave shown in a randomized double-blind trial that metforminhas an insulin-sparing effect in type 1 diabetic patients (evenif the studied population was not clinically insulin resistant)(2).

The selected patients were C-peptide negative after intravenousglucagon injection and were not identified as having metabolicsyndrome. The patients were moderately overweight (BMI closeto 25 kg/m²), and their daily insulin needs were not greaterthan that seen for other type 1 diabetic patients. The insulin-sparingeffect of metformin was obtained for basal insulin needs butnot for prandial needs. Although no definitive explanation couldbe given, it is now clear that the use of metformin may be appropriatefor some type 1 diabetic patients.

Our study was designed to assess the insulin-sparing effectof metformin in insulin-treated type 1 diabetic patients, andthis end was achieved. However, it was not designed to giveclinical or biological criteria of indications associated withmetformin use and insulin. We found that a subset of patientshad a reduction of at least 20% in insulin requirements withstable and satisfactory glucose control, but a backward logisticregression did not allow prediction criteria of a good responseto be defined. Thus, an expanded study using selection criteriaidentified in our previous study coupled with a larger rangeof BMI or bodyweight and a larger range of daily insulin dosesin selected patients must be performed to determine therapeuticindications of this association

We believe that metformin use could be beneficial in type 1diabetic patients who are overweight or obese, are receivinglarge doses of insulin, and have an HbA_1c >8%. The use ofmetformin could be very useful in these patients but must becarried out under clinical and biological supervision to avoidcomplications such as lactic acidosis, which remains exceptionalin our experience of type 1 and in type 2 diabetic patients.

Footnotes

Address correspondence to Laurent Meyer, Service de Diabétologie,Maladies Métaboliques & Maladies de la Nutrition,CIC-INSERM, Hôpital Jeanne d’Arc, Centre Hospitalo-Universitairede Nancy, B.P. 303, 54201 Toul Cedex, France. E-mail: laurentmeyer{at}hotmail.com.

References

Wulffelé MG, Kooy A, Lehert P, Bets D, Ogterop JC, Borger van der Burg B, Donker AJ, Stehouwer CD: Combination of insulin and metformin in the treatment of type 2 diabetes. Diabetes Care 25:2133–2140, 2002[Abstract/Free Full Text]
Meyer L, Böhme P, Delbachian I, Lehert P, Cugnardey N, Drouin P, Guerci B: The benefits of metformin therapy during continuous subcutaneous insulin infusion treatment of type 1 diabetic patients. Diabetes Care 25:2153–2158, 2002[Abstract/Free Full Text]