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Kidney Week

Abstract: PO0545

Metformin and the Risk of Lactic Acidosis in Patients with CKD Stage 3

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Sahinoz, Melis, VUMC, Nashville, Tennessee, United States
  • Ramos, Everly, VUMC, Nashville, Tennessee, United States
  • Pena, Carlos O., Universidad Central de Venezuela, Caracas, Distrito Capital, Venezuela, Bolivarian Republic of
  • Akwo, Elvis A., VUMC, Nashville, Tennessee, United States
  • Yu, Zhihong, VUMC, Nashville, Tennessee, United States
  • Siew, Edward D., Nashville VAMC, Nashville, Tennessee, United States
  • Roumie, Christianne, Nashville VAMC, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, VUMC, Nashville, Tennessee, United States
  • Hung, Adriana, Nashville VAMC, Nashville, Tennessee, United States
Background

Metformin has become the first-line therapy for the treatment of diabetes in patients with CKD stage 3. The use of metformin in CKD has been debated due to safety concerns related to lactic acidosis.

Methods

We assessed the safety of metformin in a double-blinded trial (NCT02252081). Fifty patients with CKD Stage 3 and metabolic syndrome and/or prediabetes were randomized to either metformin or placebo for 16 weeks. Metformin was started at 500 mg and titrated in 1-2 weeks up to 1500 mg/day in CKD 3a and 1000 mg/day in CKD 3b. Lactic acid (LA) levels were measured at weeks 2, 4, 8, 12, and 16. We compared the effect of metformin on LA between groups and over time using a mixed model and on plasma HCO3- and anion GAP (AG) using ANCOVA of change analysis.

Results

The mean age was 65±10 years old, 80% were male, BMI was 31.4±5.1 kg/m2, 16% of patients were CKD Stage 3b. LA levels slightly increased with metformin, but in most patients remained within normal limits (≤2.5 mEq/L) [Figure 1 ;p=0.054]. The association of metformin and LA remained non-significant in the multivariable-adjusted mixed model (β= 0.15, p=0.07) and remained steady over time (β= -0.003, p=0.54) . Baseline eGFR had no effect on LA levels (β= 0.01, p=0.35), whereas higher BMI was associated with higher LA levels (β=0.02, p=0.03). Only 3 patients developed LA levels >3 mEq/L: 2 at week 2 which led to drug discontinuation and 1 at week 12 which was transient. The changes in HCO3- levels and AG were not statistically significant [(HCO3-: Metformin baseline 27±2.1 mEq/L, week 16 26.2 ± 2.8 mEq/L; placebo baseline 26.2±2.1 mEq/L, week 16 26.7±2.8 Eq/L; p=0.21) (AG: Metformin baseline 10.1±2.2 mEq/L, week 16 10.4±2.1 mEq/L; placebo baseline AG 10.4±2.2 mEq/L, week 16 9.9±2.3 mEq/L, p=0.42)].

Conclusion

Metformin use in patients with CKD stage 3 appears to be safe. LA levels mildly increased with metformin, but remained within normal limits and stable after week 2. Patients did not develop clinical or laboratory manifestations of acidosis based on HCO3- levels and AG.

Funding

  • Veterans Affairs Support