Cyclocreatine, a creatine analog that easily cross blood‐brain barriers and enter the brain, can maintain cellular ATP levels in need of energy,[14] and has shown protective effects in a variety of diseases, such as heart failure,[30] prostate cancer,[31] and neurodegenerative disorders.[32] Our study further confirmed that, in either WT or Trem2 deficient microglia, supplementation of cyclocreatine under the circumstance of hypoxia in vitro was beneficial for maintaining normal functions and metabolic profiles via the upregulation of Igf1 expression. The gene discussed is TREM2; the disease is heart failure.