Metformin in Patients With Type 2 Diabetes and Kidney Disease

Abstract

IMPORTANCE Metformin is widely viewed as the best initial pharmacological option to lower glucose concentrations in patients with type 2 diabetes mellitus. However, the drug is contraindicated in many individuals with impaired kidney function because of concerns of lactic acidosis. OBJECTIVE To assess the risk of lactic acidosis associated with metformin use in individuals with impaired kidney function. EVIDENCE ACQUISITION In July 2014, we searched the MEDLINE and Cochrane databases for English-language articles pertaining to metformin, kidney disease, and lactic acidosis in humans between 1950 and June 2014. We excluded reviews, letters, editorials, case reports, small case series, and manuscripts that did not directly pertain to the topic area or that met other exclusion criteria. Of an original 818 articles, 65 were included in this review, including pharmacokinetic/metabolic studies, large case series, retrospective studies, meta-analyses, and a clinical trial. RESULTS Although metformin is renally cleared, drug levels generally remain within the therapeutic range and lactate concentrations are not substantially increased when used in patients with mild to moderate chronic kidney disease (estimated glomerular filtration rates, 30-60 mL/min per 1.73 m2). The overall incidence of lactic acidosis in metformin users varies across studies from approximately 3 per 100 000 person-years to 10 per 100 000 person-years and is generally indistinguishable from the background rate in the overall population with diabetes. Data suggesting an increased risk of lactic acidosis in metformin-treated patients with chronic kidney disease are limited, and no randomized controlled trials have been conducted to test the safety of metformin in patients with significantly impaired kidney function. Population-based studies demonstrate that metformin may be prescribed counter to prevailing guidelines suggesting a renal risk in up to 1 in 4 patients with type 2 diabetes mellitus—use which, in most reports, has not been associated with increased rates of lactic acidosis. Observational studies suggest a potential benefit from metformin on macrovascular outcomes, even in patients with prevalent renal contraindications for its use. CONCLUSIONS AND RELEVANCE Available evidence supports cautious expansion of metformin use in patients with mild to moderate chronic kidney disease, as defined by estimated glomerular filtration rate, with appropriate dosage reductions and careful follow-up of kidney function.

Anti-diabetic activity of stigmasterol from soybean oil by targeting the GLUT4 glucose transporter

“…The successfully established diabetic KK-Ay mice ( n  = 41) were randomly divided into four groups: vehicle group (saline treatment, n  = 10); SMR-treated groups (50 mg/kg/day, n  = 10; 100 mg/kg/day, n  = 11). As we all known, metformin is a commonly used anti-diabetic drug which has been demonstrated can increasing GLUT4 expression and translocation through activating AMPK pathway [28,29]. So we choose metformin as a positive control drug (200 mg/kg/day, n  = 10).…”

60 years of metformin use: a glance at the past and a look to the future

“…Indeed, many people have suggested that the contraindication of metformin use in chronic kidney disease stage 3 and beyond (estimated GFR [eGFR] <60 ml min −1 [1.73 m] −2 ) is too restrictive. A further meta-analysis, however, supports the cautious use of metformin in individuals with chronic kidney disease with an eGFR as low as 30 ml min −1 [1.73 m] −2 , with appropriate dose reductions and meticulous ongoing measurement of renal function [7]. However, there is a very small but real risk of lactic acidosis particularly in individuals taking metformin who develop acute kidney injury [8].…”

Metformin: clinical use in type 2 diabetes

“…In line with this, in an often-cited meta-analysis involving prospective and retrospective studies, the risk of MALA with metformin was found to be negligible. In fact, in most circumstances, so long as the estimated GFR (eGFR) was >30 ml min −1 [1.73 m] −2 , circulating drug levels remained within the safe range [38].…”