Carlos A Alvarez1,2,3, Ethan A Halm2, Mary Jo V Pugh4, Darren K McGuire2, Sean Hennessy5, Richard T Miller2,3, Ildiko Lingvay2, Scott M Vouri6, Andrew R Zullo7, Hui Yang1, Matt Chansard2, Eric M Mortensen2,3,8. 1. Texas Tech University Health Sciences Center School of Pharmacy Dallas TX USA. 2. University of Texas Southwestern Medical Center Dallas TX USA. 3. Veterans Affairs North Texas Health Care System Dallas TX USA. 4. University of Utah School of Medicine Salt Lake City UT USA. 5. University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. 6. University of Florida College of Pharmacy Gainesville FL USA. 7. Brown University School of Public Health and Providence Veterans Affairs Medical Center Providence RI USA. 8. University of Connecticut School of Medicine Farmington CT USA.
Abstract
Objective: Compare rates of lactic acidosis (LA) among metformin-exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD). Research Design and Methods: Retrospective, nested case-control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003-13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications. Results: Overall, 320 882 patients were included, contributing a total of 1 331 784 person-years of follow-up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93-2.08) per 1000 person-years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69-2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71-1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19-4.35 in CKD 3a, HR 3.34, 95% CI 1.95-5.72 in CKD 3b, HR 7.87, 95% CI 3.51-17.61 in CKD stage 4&5. Conclusion: Metformin was not associated with an elevated risk of LA in persons with stage 1-2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.
Objective: Compare rates of lactic acidosis (LA) among metformin-exposed and unexposed patients with type 2 diabetes mellitus and varying degrees of chronic kidney disease (CKD). Research Design and Methods: Retrospective, nested case-control study using data from national VA Corporate Data Warehouse. All adult patients with type 2 diabetes and CKD newly dispensed any antihyperglycaemic medication during FY 2003-13 were included. The outcome was LA hospitalization or serum lactate >5 mEq/L. Exposure to metformin was evaluated in the three months prior to event. Estimates were adjusted for 31 covariates, including demographics, comorbidities and medications. Results: Overall, 320 882 patients were included, contributing a total of 1 331 784 person-years of follow-up. LA occurred in 2 665 patients, generating an overall incidence rate of 2.00 (95% CI 1.93-2.08) per 1000 person-years. Metformin exposure in the prior 3 months was associated with an elevated adjusted hazard of LA (HR 1.97, 95% CI 1.69-2.29). No association was evident in patients with CKD stage 1 or 2 (HR 1.05, 95% CI 0.71-1.57), but associations were present and progressively greater in patients with CKD stage 3a through 5: HR 3.09, 95% CI 2.19-4.35 in CKD 3a, HR 3.34, 95% CI 1.95-5.72 in CKD 3b, HR 7.87, 95% CI 3.51-17.61 in CKD stage 4&5. Conclusion:Metformin was not associated with an elevated risk of LA in persons with stage 1-2 CKD, but was associated with a progressively higher risk at more advanced stages of CKD.
Authors: Benjamin Lazarus; Aozhou Wu; Jung-Im Shin; Yingying Sang; G Caleb Alexander; Alex Secora; Lesley A Inker; Josef Coresh; Alex R Chang; Morgan E Grams Journal: JAMA Intern Med Date: 2018-07-01 Impact factor: 21.873
Authors: Michael Bodmer; Christian Meier; Stephan Krähenbühl; Susan S Jick; Christoph R Meier Journal: Diabetes Care Date: 2008-09-09 Impact factor: 17.152
Authors: Melanie J Davies; David A D'Alessio; Judith Fradkin; Walter N Kernan; Chantal Mathieu; Geltrude Mingrone; Peter Rossing; Apostolos Tsapas; Deborah J Wexler; John B Buse Journal: Diabetes Care Date: 2018-10-04 Impact factor: 19.112