Christianne L Roumie1,2, Jonathan Chipman3, Jea Young Min1,4, Amber J Hackstadt3, Adriana M Hung1,2, Robert A Greevy3, Carlos G Grijalva1,4, Tom Elasy1,2, Marie R Griffin1,2,4. 1. Veteran Administration Tennessee Valley VA Health Care System Geriatric Research Education Clinical Center, Nashville. 2. Department of Medicine, Vanderbilt University Medical Center, Nashville. 3. Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee. 4. Department of Health Policy, Vanderbilt University Medical Center, Nashville, Tennessee.
Abstract
IMPORTANCE: Before 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown. OBJECTIVE: To compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016). EXPOSURES: New users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function. MAIN OUTCOMES AND MEASURES: MACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death. RESULTS: There were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use. CONCLUSIONS AND RELEVANCE: Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.
IMPORTANCE: Before 2016, safety concerns limited metformin use in patients with kidney disease; however, the effectiveness of metformin on clinical outcomes in patients with reduced kidney function remains unknown. OBJECTIVE: To compare major adverse cardiovascular events (MACE) among patients with diabetes and reduced kidney function who continued treatment with metformin or a sulfonylurea. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of US veterans receiving care within the national Veterans Health Administration, with data supplemented by linkage to Medicare, Medicaid, and National Death Index data from 2001 through 2016. There were 174 882 persistent new users of metformin and sulfonylureas who reached a reduced kidney function threshold (estimated glomerular filtration rate <60 mL/min/1.73 m2 or creatinine ≥1.4 mg/dL for women or ≥1.5 mg/dL for men). Patients were followed up from reduced kidney function threshold until MACE, treatment change, loss to follow-up, death, or study end (December 2016). EXPOSURES: New users of metformin or sulfonylurea monotherapy who continued treatment with their glucose-lowering medication after reaching reduced kidney function. MAIN OUTCOMES AND MEASURES: MACE included hospitalization for acute myocardial infarction, stroke, transient ischemic attack, or cardiovascular death. The analyses used propensity score weighting to compare the cause-specific hazard of MACE between treatments and estimate cumulative risk accounting for the competing risks of changing therapy or noncardiovascular death. RESULTS: There were 67 749 metformin and 28 976 sulfonylurea persistent monotherapy users; the weighted cohort included 24 679 metformin and 24 799 sulfonylurea users (median age, 70 years [interquartile range {IQR}, 62.8-77.8]; 48 497 men [98%]; and 40 476 white individuals [82%], with median estimated glomerular filtration rate of 55.8 mL/min/1.73 m2 [IQR, 51.6-58.2] and hemoglobin A1c level of 6.6% [IQR, 6.1%-7.2%] at cohort entry). During follow-up (median, 1.0 year for metformin vs 1.2 years for sulfonylurea), there were 1048 MACE outcomes (23.0 per 1000 person-years) among metformin users and 1394 events (29.2 per 1000 person-years) among sulfonylurea users. The cause-specific adjusted hazard ratio of MACE for metformin was 0.80 (95% CI, 0.75-0.86) compared with sulfonylureas, yielding an adjusted rate difference of 5.8 (95% CI, 4.1-7.3) fewer events per 1000 person-years of metformin use compared with sulfonylurea use. CONCLUSIONS AND RELEVANCE: Among patients with diabetes and reduced kidney function persisting with monotherapy, treatment with metformin, compared with a sulfonylurea, was associated with a lower risk of MACE.
Authors: Godela M Brosnahan; Wei Wang; Berenice Gitomer; Taylor Struemph; Diana George; Zhiying You; Kristen L Nowak; Jelena Klawitter; Michel B Chonchol Journal: Am J Kidney Dis Date: 2021-08-12 Impact factor: 8.860
Authors: Gianfrancesco Fiorini; Ivan Cortinovis; Giovanni Corrao; Matteo Franchi; Angela Ida Pincelli; Mario Perotti; Antonello Emilio Rigamonti; Alessandro Sartorio; Silvano Gabriele Cella Journal: Int J Environ Res Public Health Date: 2020-11-05 Impact factor: 3.390
Authors: Romain Neugebauer; Emily B Schroeder; Kristi Reynolds; Julie A Schmittdiel; Linda Loes; Wendy Dyer; Jay R Desai; Gabriela Vazquez-Benitez; P Michael Ho; Jeff P Anderson; Noel Pimentel; Patrick J O'Connor Journal: JAMA Netw Open Date: 2020-01-03