The use of metformin in patients with renal impairment
Abstract
Metformin, a biguanide, is widely accepted to be the preferred first-line oral antihyperglycaemic agent to manage type 2 diabetes. There is considerable concern that patients receiving metformin therapy may be at an increased risk of developing lactic acidosis. The risk has traditionally been assumed to be increased in patients with chronic renal impairment, resulting in many patients being denied access to an effective first-line treatment agent. The overarching aims of this thesis were to explore the safe use of metformin and to create a renal dosing guideline that will mitigate the risk of lactic acidosis. \nThe safe use of metformin was explored by formally evaluating the association between metformin therapy and lactic acidosis in published case reports of metformin associated lactic acidosis (MALA) using two causality assessments. Metformin was found to play only a possible role in the development of lactic acidosis based on the results from the causality assessments. Almost all cases presented with other risk factors that could on their own have caused lactic acidosis. \nA subgroup analysis was performed in MALA cases with a history of chronic renal impairment to explore the relationship between metformin dose, plasma concentration and lactic acidosis. Most cases presented with acute renal failure, confounding the relationship between metformin dose and plasma concentrations. The prescribed metformin dose exceeded the dosing recommendations in over 60% of cases with…
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