Metformin & Chronic Kidney Disease (CKD) : a reassessment of the benefit/risk ratio ; Metformine et insuffisance rénale : réévaluation du rapport bénéfices-risques

Although metformin is acknowledged as having a pivotal role in the treatment of type II diabetes mellitus, there is still a debate concerning the drug's beneficial and adverse effects. The purpose of the present work was three-fold: (i) To perform a critical, qualitative examination of reports of so-called MALA, with a focus on the criteria for the definition of MALA, the prognostic value of the latter criteria in severe MALA, and the mortality rate; (ii) To examine the advantages and limitations of measuring metformin concentrations in blood (plasma and erythrocytes) when screening for metformin accumulation and assessing its extent and consequences; and (iii) to conduct an open-label pilot study with metformin therapy in patients at all chronic kidney disease (CKD) stages. Patients underwent 1 week-blocks of metformin treatment at an increasing dosage (each block followed by a 1 week-wash-out period). Metformin levels were measured in plasma and in erythrocytes (the tissue compartment) according to metformin dosage and CKD severity. Lactate levels were also measured. A progressive dose-related increase of the trough metformin levels was observed, more pronounced in moderate to severe CKD. There was no case of significant hyperlactatemia. Our conclusion is that it may be possible to continue metformin therapy under safe conditions in patients with CKD (and even severe CKD), provided that the metformin dose is appropriately adjusted. We are waiting for the results of a complementary, follow-up study, conducted over 4 months, with a fixed and adapted dose to the renal function of metformin to provide a solid basis for the adoption of metformin therapy in CKD ; La metformine est reconnue comme le traitement de première intention dans le diabète de type 2 mais le débat relatif à la balance bénéfice/risque demeure vif, concernant en particulier le sujet insuffisant rénal. Le but du présent travail était triple : 1) mener une analyse critique des rapports d'acidose lactique associée à la metformine, et plus ...