PracticeUpdate: Diabetes

EDITOR’S PICKS 7

Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney

Function JAMA Internal Medicine

Take-home message • In this community-based cohort study of 75,413 people with diabetes, the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR) was investigated. Over a median of 5.7 years of follow-up, 2335 hospitalizations with acidosis were reported. No associations were reported between time-dependent metformin use and overall incident acidosis or in patients with eGFR between 30 and 59 mL/min/1.73 m 2 . Metformin use was associated with an increased acidosis risk in patients with eGFR below 30 mL/min/1.73 m 2 . • These findings support cautious use of metformin in individuals with type 2 diabetes and an eGFR above 30 mL/min/1.73 m 2 . Abstract

in Geisinger Health System, with time-depend- ent assessment of eGFR stage from January 2004 until January 2017. Results were replicated in 67 578 new metformin users and 14 439 new sulfonylurea users from 2010 to 2015, sourced from 350 private US health systems. EXPOSURES Metformin use. MAIN OUTCOMES AND MEASURES Hospitalization with acidosis (International Classification of Dis- eases, Ninth Revision, Clinical Modification code of 276.2). RESULTS In the primary cohort (n = 75 413), mean (SD) patient age was 60.4 (15.5) years, and 51% (n = 38 480) of the participants were

IMPORTANCE Approximately 1 million patients in the United States with type 2 diabetes mellitus and mild-to-moderate kidney disease do not receive guideline-directed therapy with met- formin. This may reflect uncertainty regarding the risk of acidosis in patients with chronic kid- ney disease. OBJECTIVE To quantify the association between metformin use and hospitalization with acidosis across the range of estimated glomerular filtra- tion rate (eGFR), accounting for change in eGFR stage over time. DESIGN, SETTING, AND PARTICIPANTS Communi- ty-based cohort of 75 413 patients with diabetes

" …findings support cautious use of metformin in individuals

with type 2 diabetes and an eGFR above 30 mL/min/1.73 m 2 . "

female. There were 2335 hospitalizations with acidosis over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years). Compared with alternative diabetes management, time-de- pendent metformin use was not associated with incident acidosis overall (adjusted hazard ratio [HR], 0.98; 95% CI, 0.89-1.08) or in patients with eGFR 45 to 59 mL/min/1.73 m 2 (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/ min/1.73 m 2 (adjusted HR, 1.09; 95% CI, 0.83- 1.44). On the other hand, metformin use was associated with an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m 2 (adjusted HR, 2.07; 95% CI, 1.33-3.22). Results were consistent when newmetformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.71; 95% CI, 0.45- 1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m 2 , 0.86; 95% CI, 0.37-2.01). CONCLUSIONS AND RELEVANCE In 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/ min/1.73 m 2 . Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m 2 . Association of Metformin Use With Risk of Lactic Acidosis Across the Range of Kidney Function: A Community-Based Cohort Study. JAMA Intern Med 2018 Jun 04;[EPub Ahead of Print], B Lazarus, A Wu, JI Shin, et al. www.practiceupdate.com/c/69282

VOL. 2 • NO. 3 • 2018