Retrospective analysis of lactic acidosis-related parameters upon and after metformin discontinuation in patients with diabetes and chronic kidney disease.
OBJECTIVE
To investigate association between renal functions, lactic acid levels and acid-base balance in type 2 diabetes patients with chronic kidney disease under metformin treatment and after metformin discontinuation in a real-life setting.


METHODS
A total of 65 patients with diabetes (mean age 68.5 ± 8.9 years, 56.9 % females) in whom metformin treatment was discontinued due to reduced glomerular filtration rate (GFR) were included in this retrospective study. Data on patient demographics, metformin treatment and laboratory findings on the last day of metformin treatment and 2-3 weeks after metformin discontinuation including blood lactate and creatinine, estimated glomerular filtration rate (eGFR) and acid-base balance measurements in blood [pH, bicarbonate, base excess] were collected from medical records. The correlation of lactate levels with eGFR, blood pH and creatinine levels and changes in laboratory findings after metformin discontinuation were evaluated.


RESULTS
Before metformin discontinuation, hyperlactatemia was observed in 78.5 % of patients and metabolic acidosis in 36.9 % of patients, but none had lactic acidosis. Patients with normolactatemia and hyperlactatemia were similar in terms of metformin dosage and laboratory parameters. Lactate levels were not significantly correlated with serum creatinine (r = -0.14; p = 0.263) and eGFR (r = 0.11, p = 0.374). After metformin discontinuation, a significant decrease was observed in median lactate levels (from 2.20 to 1.85 mmol/L; p = 0.002).


CONCLUSIONS
In conclusion, our findings support the low risk of MALA among patients with mild-to-moderate renal impairment and the likelihood of metformin to be an innocent bystander without a pathogenic role in the lactic acidosis in most cases.
Division of Nephrology, Department of Internal Medicine, Sakarya University Faculty of Medicine, Adnan Menderes Cd. Saglik Sok. No: 195, 54100, Adapazari/Sakarya, Turkey. ssipahi@sakarya.edu.tr.
Savas
S
Sipahi
Division of Nephrology, Department of Internal Medicine, Sakarya University Faculty of Medicine, Adnan Menderes Cd. Saglik Sok. No: 195, 54100, Adapazari/Sakarya, Turkey.
Yalcin
Y
Solak
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Seyyid Bilal
SB
Acikgoz
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Ahmed Bilal
AB
Genc
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Mehmet
M
Yildirim
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Ulku
U
Yilmaz
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Ahmet
A
Nalbant
Department of Internal Medicine, Sakarya University Faculty of Medicine, Sakarya, Turkey.
Ali
A
Tamer
D000140:Acidosis, Lactic / Q000139:chemically induced* / Q000453:epidemiology; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015897:Comorbidity; D003404:Creatinine / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects*; D008875:Middle Aged; D051437:Renal Insufficiency / Q000139:chemically induced / Q000453:epidemiology / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000175:diagnosis / Q000453:epidemiology* / Q000628:therapy; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D028761:Withholding Treatment
D007004:Hypoglycemic Agents; D008687:Metformin; D003404:Creatinine
Diabetes mellitus; Lactic acidosis; Metformin; Renal failure