In the CREATE trial a significant higher rate of hypoglycemia was observed in erythropoietin treated patients (N Engl J Med.355:2071). We therefore tested the hypothesis that the erythropoietin derivate (C.E.R.A.) is able to reduce insulin resistance.

Obese, diabetic db/db mice received C.E.R.A. (4.5 mg/kg, once weekly, s.c.). 0.9%NaCl treated animals served as control. After two weeks of C.E.R.A.-treatment a significant and persistent reduction of fasting glucose, HbA1c, fasting insulin and HOMA index was detected. These changes correlated strongly to the hematocrit(HCT)level. Normalization of the increased HCT in the C.E.R.A. treated animals by bleeding led to an increase of the blood glucose level to the same values as in the untreated animals within 30 min., suggesting that the increased HCT plays a crucial role in the improved glycemic control. The total glucose-6- phosphate and 6-phosphogluconate dehydrogenase activity was significantly increased in blood of C.E.R.A.-treated mice. However, the HCT corrected glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were not increased. In conclusion, C.E.R.A. is able to reduce hyperglycemia by increasing the erythrocyte number.