Clinical question: Does the continuation of metformin during hospitalization result in fewer post-hospitalization complications, such as hypoglycemia or death?
Background: Despite metformin’s first-line role in the management of type 2 diabetes, it is common clinical practice, supported by professional guidelines, to hold metformin in the inpatient setting due to concern for lactic acidosis. However, this association has been disputed in several studies and is based primarily on data from the older related drug phenformin. The benefits of the continuation of metformin have not been robustly studied.
Study design: Observational cohort study with target trial emulation
Setting: 114 Veterans Health Administration (VHA) hospitals in the U.S.
Synopsis: Using the VHA Corporate Data Warehouse, patients with type 2 diabetes prescribed metformin and admitted to a VHA hospital from 2016 to 2022 were identified (96.9% male). Exclusion criteria were a glomerular filtration rate less than 30 mL/min/1.73 m2 or death during hospitalization. After propensity score matching, 33,581 patients who received metformin at any point during their hospitalization were compared with an equal number for whom metformin was held. Interestingly, practice patterns varied considerably, with the proportion of patients continued on metformin ranging from 6.3 to 76.6% across hospitals. Those who received metformin had significantly fewer post-discharge hypoglycemic events, the primary outcome (1.5% versus 1.8%; OR, 0.83; 95% CI, 0.73-0.93; P=0.003). They also had significantly lower 90-day mortality (6.4% versus 7.4%), risk of readmission (29.4% versus 30.6%), and fewer new insulin prescriptions. Limitations include residual confounding, single health-system data, and lack of information on when metformin was initiated during the hospital stay in the metformin continuation arm of the study.
Bottom line: Though absolute risk reduction was modest, this large study shows an association with improved post-discharge outcomes when metformin is continued during hospitalization. Given no evidence of significant adverse events in prior studies, continuation of metformin should be considered during hospital stay, with the caveat that optimal time of introduction (at admission versus mid or late hospitalization) is not addressed in this study and needs to be further evaluated.
Citation: Gallo RJ, et al. Inpatient metformin utilization and post-hospitalization clinical outcomes: an observational cohort study. J Gen Intern Med. 2025. doi:10.1007/s11606-025-09384-y.
Dr. Wood is a hospital medicine attending physician at Maine Medicine Center in Portland, Maine, and an assistant professor at Tufts University School of Medicine in Boston