Association of Metformin Use With End‐Stage Renal Disease in Patients With Type 2 Diabetes Mellitus: A Nationwide Cohort Study Under the Pay‐for‐Performance Program

Abstract

Animal studies have demonstrated that metformin exerts a renoprotective effect. Human studies of patients with diabetes mellitus (DM) regarding the association of metformin use with end‐stage renal disease (ESRD) are lacking. Patients with type 2 DM and without a history of kidney disease who were enrolled under the pay‐for‐performance program of the National Health Insurance in Taiwan were identified. Those who received ≥90 cumulative defined daily doses of metformin within 1 year were selected (metformin users) and compared with a 1:1 propensity score–matched metformin nonuser cohort. Primary and secondary outcomes were development of ESRD and chronic kidney disease (CKD), respectively. Independent predictors were investigated using Cox regression analysis. A total of 24 158 pairs of metformin users and nonusers were enrolled, with an incidence of ESRD of 1908 and 1723 and CKD of 1095 and 1056 cases per 100 000 person‐years, respectively. Metformin use was independently associated with increased risks of ESRD (adjusted hazard ratio, 1.22; 95% confidence interval, 1.12‐1.32) and CKD (adjusted hazard ratio, 1.25; 95% confidence interval, 1.12‐1.40) in a dose‐response relationship. Patients with hypertension plus nonuse of angiotensin‐converting enzyme inhibitors or angiotensin II receptor blockers potentiated kidney damage by metformin. In patients with DM, use of metformin may increase the risk of ESRD and CKD. Health care professionals should be alert and closely monitor renal function when prescribing metformin.

The Current and Potential Therapeutic Use of Metformin—The Good Old Drug

“…The aim of that study was to assess the impact of metformin on the development of end-stage kidney disease and CKD. The findings indicate that among metformin users vs. non-users the risk of the end-stage kidney disease and CKD development was 22% and 25% higher, respectively [234].…”

Metformin and cardiorenal outcomes in diabetes: A reappraisal

“…These findings may have been driven mainly by the effect of metformin on mortality, as the analysis was neutral for ESRD as an individual outcome. A study of 24 158 matched pairs of metformin users and non‐users from the Taiwan National Health Insurance database suggested a small but significant increase in the risk of ESRD with metformin . Interestingly, in a recent subgroup analysis of the EMPA‐REG Outcome trial, it was suggested that renoprotection with empagliflozin might be attenuated by background metformin therapy on the basis that there was a non‐significant trend ( P for interaction = 0.07) towards higher hazard ratios for nephropathy events with concomitant metformin therapy (0.68 [95% CI 0.58 to 0.79]) compared with no metformin therapy (0.47 [95% CI 0.37 to 0.59]) .…”

The impact of metformin in chronic kidney disease-mineral and bone disorder

“…Based on a study by Richy et al, the administration of metformin showed no difference in the prevalence of lactic acidosis in patients with T2D who had normal, mild, moderate, or severe renal dysfunction (44). Recently, a retrospective observational cohort study by Lee et al, reported that metformin users probably develop ESRD and CKD more than non-metformin users (45). While Lalau et al reported no adverse effects for the use of metformin in different CKD stages (46).…”