Metformin is associated with increase in lactate level in elderly patients with type 2 diabetes and CKD stage 3: A case-control study

J Diabetes Complications. 2020 Jan;34(1):107474. doi: 10.1016/j.jdiacomp.2019.107474. Epub 2019 Oct 31.

Abstract

The FDA has recently endorsed metformin use in patients with T2D and stage 3 CKD (CKD3). However, metformin safety in elderly individuals is unknown. The aim of this study was to identify frequency and risk factors of lactic acid (LA) elevation in ambulatory elderly male US veterans with stable diabetic CKD3 treated with metformin. We studied 92 patients with non-diabetic CKD3 (Group1), diabetic CKD3 not on metformin (Group2) and diabetic CKD3 on metformin (Group 3). Mean LA levels were similar at 1.3 ± 0.3 and 1.3 ± 0.4 mmol/L in Groups 1 and 2, respectively; while, LA was significantly higher in Group 3 (2.1 ± 1.0 mmol/L, P < .001). Only 1 patient in each Groups 1 (4%) and 2 (4%) had hyperlactatemia (LA > 2.0 mmol/L), as compared with 17 (42.5%) patients in Group 3 (P < .05). No differences in age, BMI, eGFR, metformin dosage, and HbA1c were seen in Group 3 patients with and without hyperlactatemia. In the multivariate logistic regression analyses, metformin use was the only factor significantly associated with hyperlactatemia (adjusted OR 25.48, P < .005). In conclusion, metformin therapy is associated with increased risk of hyperlactatemia in elderly men with diabetic CKD3.

Keywords: Chronic kidney disease; Lactate; Metformin.

MeSH terms

  • Age Factors
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / complications
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / pathology
  • Disease Progression
  • Humans
  • Hyperlactatemia / chemically induced
  • Hyperlactatemia / epidemiology
  • Lactic Acid / blood*
  • Male
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / epidemiology
  • United States / epidemiology
  • Veterans / statistics & numerical data

Substances

  • Lactic Acid
  • Metformin