Changes in metformin use in chronic kidney disease

Abnormal renal function continues to be the greatest contraindication against metformin. Until the beginning of 2016, US FDA guidelines contradicted the use of male serum creatinine (Cr) above 132.63 μmol / L (1.5 mg / dL) and women over 1.4.7 mg / dL. It is well known that serum Cr readings do not accurately reflect glomerular filtration rate (GFR) [20]. Larau et al. Metformin at 30-60 mL / min 850 mg per day One group of patients receiving creatinine clearance (CrCl) and another group receiving 1700 mg metformin per day and more than 60 mL / min CrCl group. There was no significant difference in serum metformin and lactate levels between the two groups [21]. In a study of 24 patients with CrCl 15 to 49 mL / min, there was no correlation between lactate and metformin levels. Two of their patients even received dialysis [22]. In another study, 393 patients with serum Cr from 132.63 μmol / L (1.5 mg / dL) to 221.05 μmol / L (2.5 mg / dL) did not take metformin and patients who continued to take metformin Patients and patients were divided. After 4 years of follow-up, no case of LA was found in any group [23].

At normal doses, the steady state plasma level of metformin is usually less than 7.8 μmol / L and the exact concentration of dangerous serum metformin is unknown. Research by Frid et al. Even at low GFR levels it has been shown that metformin levels rarely exceed 20 μmol / L (this is a safe level [24]). However, it is not completely known whether the measurement of metformin levels predicts LA. Furthermore, there was no correlation between kidney function, metformin level, and LA.

In the final Cochrane analysis, there was no other Cr concentration. However, 45% of patients did not rule out patients with Cr> 132.63 μmol / L (1.5 mg / dL). This corresponds to 37 360 patient years of metformin in patients with chronic kidney disease (CKD), but it did not cause LA [15].

Researchers conducted extensive observational studies in studies to alleviate atherosclerosis and sustained health (REACH) studies of 19,000 subjects with a history of atherothrombotic thrombosis. In this study, GFR was 30-60 mL / min / m 2, but still 1,572 patients were taking metformin. After adjusting the baseline and propensity score, metformin was associated with a significant reduction in 2-year mortality including CKD patients. Moderate renal dysfunction (CrCl 30 - 59 mL / min / 1.73 m 2) reduced mortality by 36%. [twenty five]

A cohort study from the Swedish National Diabetes Registry reviewed 51,675 patients with DM2. The average follow-up period was 9 years. Compared to other treatments, metformin showed a 13% reduction in all-cause mortality in patients with GFR of 45-60 mL / min / 1.73 m 2. A similar effect was not observed with GFR as low as 30 to 45 mL / min / m 2, but there was no increase in the risk of acidosis [26].

Since April 2016, the FDA finally demanded a change in the label of Metformin. It is advisable to measure GFR instead of serum Cr before starting metformin. In some patients, metformin is tolerated with a GFR of 30 mL / min / 1.73 m 2, but it is not recommended to start metformin in patients with a GFR of 30 - 45 mL / min / m 2

Although the estimated risk of metformin may be amplified in the context of progressive chronic kidney disease or renal replacement therapy, in these same patients the benefits of metformin may be amplified by an increase in cardiovascular risk burden There is sex (although the underlying pathophysiology of cardiovascular disease) is different). In the absence of a randomized controlled trial using metformin in these specific populations, it is difficult to judge efficacy and safety. This should be further investigated through targeted studies, efficacy can be evaluated as part of a randomized controlled trial, safety assessed by national directory analysis It will be good. Clear regulatory recommendations on the use of metformin for renal failure between different authorities (Figure 1). This reflects that there is no strong evidence in the published guidelines.

A: As an endocrinologist, I take care of people with diabetes. Chronic kidney disease is a common complication of diabetes, and unfortunately patients with chronic kidney disease could not use metformin in the past. I have many patients whose renal function worsens over time and we have to stop Metformin. Metformin seems to be safe from the viewpoint of lactic acidosis of mild to moderate chronic kidney disease, but also seems to be associated with a lower mortality rate and it really seems that we enter the clinical setting I will help. I already have it - I was able to resume metformin for some patients who previously invalidated it