Lazarus B, et al. - In 2 real-world clinical settings, researchers investigated how metformin use is associated with hospitalization with acidosis across the range of estimated glomerular filtration rate (eGFR), accounting for change in eGFR stage over time. Metformin use was noted to have an association with acidosis only at eGFR less than 30 mL/min/1.73 m². Results thus suggest practicing caution while using metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73 m².

Methods

• From January 2004 until January 2017, researchers analyzed a community-based cohort of 75,413 patients with diabetes in Geisinger Health System, with time-dependent assessment of eGFR stage.
• From 2010 to 2015, replication of results was performed in 67,578 new metformin users and 14,439 new sulfonylurea users, sourced from 350 private US health systems.
• They assessed hospitalization with acidosis as main outcomes and measures  (International Classification of Diseases, Ninth Revision, Clinical Modification code of 276.2).

Results

• Mean (SD) patient age of the primary cohort (n=75,413) was 60.4 (15.5) years; 51% (n=38,480) of the participants comprised female.
• Over a median follow-up of 5.7 years (interquartile range, 2.5-9.9 years), 2335 hospitalizations with acidosis were noted.
• Compared with alternative diabetes management, there appeared no association of time-dependent metformin use 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 m² (adjusted HR, 1.16; 95% CI, 0.95-1.41) and eGFR 30 to 44 mL/min/1.73 m² (adjusted HR, 1.09; 95% CI, 0.83-1.44).
• On the other hand, an increased risk of acidosis at eGFR less than 30 mL/min/1.73 m² was observed in association with metformin use (adjusted HR, 2.07; 95% CI, 1.33-3.22).
• Researchers noted that results remained consistent when new metformin users were compared with new sulfonylurea users (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.77; 95% CI, 0.29-2.05), in a propensity-matched cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.71; 95% CI, 0.45-1.12), when baseline insulin users were excluded (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 1.16; 95% CI, 0.87-1.57), and in the replication cohort (adjusted HR for eGFR 30-44 mL/min/1.73 m2, 0.86; 95% CI, 0.37-2.01).