Journal Article

Risk of acute kidney injury and survival in patients treated with Metformin: an observational cohort study

McKnight, John, Petrie, John R, Farran, Bassam, Lindsay, Robert, McCrimmon, Rory J., Sattar, Naveed, Leese, Graham P, Wild, Sarah, Colhoun, Helen M., McKeigue, Paul, Bell, Samira, Looker, Helen, McGurnaghan, Stuart

2017

Overview

Background Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least  26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p  = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p  = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA 1c and diabetes duration. Conclusions Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Acidosis / Acidosis, Lactic - etiology / Acidosis, Lactic - mortality / Acute kidney injury / Acute Kidney Injury - etiology / Acute Kidney Injury - mortality / Age / Age Distribution / Aged / Antidiabetics / Biochemistry / Cohort analysis / Cohort Studies / Collaboration / Comorbidity / Creatinine / Death / Diabetes / Diabetes mellitus / Diabetes Mellitus, Type 2 - drug therapy / Diabetes Mellitus, Type 2 - mortality / Drug dosages / Drug stores / Drug-Related Side Effects and Adverse Reactions - mortality / Electronic medical records / Epidemiology / Epidemiology and Health Outcomes / Epidermal growth factor receptors / Female / Health maintenance organizations / Health risk assessment / HMOs / Humans / Incidence / Internal Medicine / Kidney diseases / Kidney transplantation / Laboratories / Lactic acidosis / Male / Medicine / Medicine & Public Health / Metformin / Metformin - adverse effects / Metformin - therapeutic use / Middle Aged / Nephrology / Observational studies / Patient admissions / Pharmaceutical industry / Pharmacy / Prescription drugs / Renal function / Research Article / Risk Factors / Scotland - epidemiology / Sex / Sex Distribution / Studies / Survival / Survival analysis / Survival Rate / Treatment Outcome