Risk for Lactic Acidosis in Type 2 Diabetes Associated With Metformin Use

Metformin use in patients with chronic kidney disease and the risk for lactic acidosis was examined.

Metformin use was associated with hospitalization for acidosis in individuals with type 2 diabetes with an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73 m2, according to a study published in JAMA Internal Medicine.

The study utilized a large, electronic, integrated medical record cohort (the Geisinger Health System) to find data on 75,413 individuals diagnosed with diabetes who were treated in the Geisinger Health System between January 2004 and January 2017. The primary study outcome was hospitalization for an acidosis event, which was identified by the inpatient ICD-9-CM code 276.2. At cohort enrollment, 14,662 patients had an eGFR <60 mL/min/1.73m2, and 1765 had an eGFR <30 mL/min/1.73m2.

At enrollment, 34,095 patients were taking metformin (45%), and 13,781 began taking it during follow-up. Median follow-up duration was 5.7 years (interquartile range 2.5-9.9). Overall, 2335 incidents of hospitalizations for acidosis occurred during 470,114 person-years of follow-up. Of these, 737 occurred during 188,578 person-years of metformin use, and 1598 occurred during 281,536 person-years of no metformin. Patients with eGFR >30 mL/min/1.7 m2 did not show elevated rates of hospitalization for acidosis, even after adjusting for eGFR stage changes over time and for confounders such as cardiovascular risk factors, demographics, concomitant medications, and glycated hemoglobin (adjusted hazard ratio [aHR] 0.98; 95% CI, 0.89-1.08). Results remained consistent when new users of metformin were compared with new users of sulfonylurea (aHR for eGFR from 30 to 44 mL/min/1.73m2, 0.77; 95% CI, 0.29-2.05), when investigators excluded baseline insulin users (aHR for eGFR from 30 to 44 mL/min/1.73m2, 1.16; 95% CI, 0.87-1.57), in a propensity-matched study cohort (aHR for eGFR from 30 to 44 mL/min/1.73m2, 0.71; 95% CI, 0.45-1.12), and in the replication study cohort (adjusted HR for eGFR from 30 to 44 mL/min/1.73m2, 0.86; 95% CI, 0.37-2.01).

Study investigators conclude, “[in] 2 real-world clinical settings, metformin use was associated with acidosis only at eGFR less than 30 mL/min/1.73m2. Our results support cautious use of metformin in patients with type 2 diabetes and eGFR of at least 30 mL/min/1.73m2.”


Lazarus B, Wu A, Shin JI, et al. Association of metformin use with risk of lactic acidosis across the range of kidney function: a community-based cohort study [published online June 4, 2018]. JAMA Intern Med. doi: 10.1001/jamainternmed.2018.0292