Lactic acidosis incidence with metformin in patients with type 2 diabetes and chronic kidney disease: A retrospective nested case-control study.

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.

• Authors: Carlos A Alvarez, Ethan A Halm, Mary Jo V Pugh, Darren K McGuire, Sean Hennessy, Richard T Miller, Ildiko Lingvay, Scott M Vouri, Andrew R Zullo, Hui Yang, Matt Chansard, Eric M Mortensen
• Journal: Endocrinology, diabetes & metabolism (Endocrinol Diabetes Metab) Vol. 4 Issue 1 Pg. e00170 (01 2021) ISSN: 2398-9238 [Electronic] England
• PMID: 33532612 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2020 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.

Chemical References

• Metformin

Topics

• Acidosis, Lactic (etiology)
• Aged
• Case-Control Studies
• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Female
• Follow-Up Studies
• Humans
• Incidence
• Male
• Metformin (adverse effects)
• Middle Aged
• Negative Results
• Propensity Score
• Renal Insufficiency, Chronic (complications)
• Retrospective Studies
• Risk
• Time Factors