Insulin or Metformin for Glucose Control during Wound Healing in Diabetes?

Abstract

Good glycemic control is crucial for the proper wound healing in diabetes. It is not clear whether there is any additional effect on wound healing of any antidiabetic drugs beyond improvement in glucose control. We conducted an experimental study aiming at assessing the effect of insulin and metformin on the wound healing. The study was performed in 45 male Wistar rats with streptozotocin-induced diabetes divided into 3 groups: group 1 received human NPH insulin intraperitoneally (5 j.m./kg b.w.) once daily, group 2 received metformin intragastrically (500 mg/kg b.w.) once daily and group 3 (controls) were given saline intraperitoneally. The treatment goal was to achieve blood glucose levels of 350-450 mg/dl in order to reflect hyperglycemic conditions often associated with wound development. After 30 days of antidiabetic treatment the rats had the thin layer of the skin cut out from the dorsal skin 2x2 cm. The wounds were assessed every 3 days with digital photography and wound biopsy. The wounds healing was followed-up for 9 days. Mean blood glucose levels in all groups after 30 days of treatment and during wound healing follow-up ranged 350 and 450 mg/dl. After 3 days healing in the rats treated with insulin was more advanced than in the control group, and it was more advanced than in the metformin group after 6 and 9 days. There were no differences between the metformin and control groups at any stage of the study. Wound tissue samples taken from the insulin treated animals presented with significantly lower level of inflammatory infiltration than those obtained from the rats treated with metformin. Immunohistochemical assessment showed the greatest density of centers of profileration in insulin treated animals. In conclusion, insulin treatment was more beneficial than metformin for the wound healing process in animal model. As the observations were made at a similar level of hyperglycemia in all groups, it might be speculated that there is an additional effect of insulin on wound healing beyond glucose lowering action. Disclosure B. Mrozikiewicz-Rakowska: None. M. Mieczkowski: None. T. Siwko: None. M. Bujalska-Zadrozny: None. T. Grzela: None. R. Wolinska: None. A.E. de Corde: None. P. Foltynski: None. L. Czupryniak: Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company. Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Merck & Co., Inc., Polpharma, Servier.