T2DM: metformin safer in stage 3 CKD than previously thought

  • Charytan DM & al.
  • Diabetes Obes Metab
  • 22 Jan 2019

  • curated by Yael Waknine
  • Clinical Essentials
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Takeaway

  • Metformin can be used safely in patients with comorbid type 2 diabetes mellitus (T2DM) and stage 3 chronic kidney disease (CKD).
  • Use can have survival and cardiovascular (CV) benefits but may not slow CKD progression.

Why this matters

  • Metformin is often withheld over concerns for lactic acidosis.

Study design

  • Study of metformin users (n=591) and nonusers (n=3447) enrolled in the TREAT trial.
  • 508 metformin users (85%) were propensity-score-matched with nonusers (CKD stage 3a, 29.5% vs 25.2%; 3b, 42.7% vs 45.3%).
  • CV composite endpoint: death, heart failure hospitalization, myocardial infarction, stroke, or myocardial ischemia.
  • Kidney disease endpoint: end-stage renal disease (ESRD) or death.
  • Funding: Amgen.

Key results

  • Metformin was associated with lower incidence (per 100 patient years) of mortality (4.6 vs 8.5), CV death (2.8 vs 5.2), CV composite endpoint (8.6 vs 11.9), and kidney disease endpoint (8.0 vs 10.9).
    • ESRD rate was marginally higher (4.0 vs 3.6).
  • In multivariate analysis, metformin use was associated with reduced:
    • All-cause mortality (HR, 0.49; P<.001>
    • CV death (HR, 0.49; P<.001>
    • CV composite endpoint (HR, 0.66; P=.002);
    • Combined endpoint of ESRD or death (HR, 0.77; P=.037).
  • Associations with ESRD were not significant (P=.98).
  • Findings were supported in adjusted analysis of the overall population.
  • 2 cases of nonfatal lactic acidosis observed.

Limitations

  • Nonrandomized metformin use.