Abstract

The use of rapid-acting insulin analogs as routes of administration other than IV has never been described for the treatment of dogs with diabetic ketoacidosis (DKA). This study aims to compare the efficacy and safety of a new protocol based on IM administration of insulin lispro with that of low-dose IV continuous rate infusion of regular insulin in the treatment of canine DKA. Client-owned dogs with naturally occurring DKA were included. Dogs treated with IM insulin lispro (Group L, n = 11) received 0.25 U/kg. The goal was to achieve a drop of at least 10% in blood glucose between 1 h and the next. If this goal was not achieved, the insulin dose was repeated hourly; otherwise, the insulin dose was not repeated up to a maximum of 3 h, after which the insulin dose was repeated anyway. When blood glucose was ≤250 mg/dL, the insulin dose was reduced to 0.125 U/kg IM every 3 h. Cases receiving IV continuous rate infusion of regular insulin (Group R, n = 13) were treated according to a previously published protocol. The median time to resolution of ketosis was significantly shorter in Group L (12 h; range, 4–27 h) compared to Group R (23 h; 10–46 h; P = 0.04). The median times to resolution of acidemia and ketoacidosis were 13 h (4–35 h) and 17.5 h (4–35 h) in Group L, and 22 h (9–80 h) and 23.5 h (10–80 h) in Group R, respectively. These differences were not significant (P = 0.06 and P = 0.09, respectively). The median length of hospitalization did not differ significantly between groups (P = 0.67). There were no differences in the frequency and severity of adverse events (hypoglycemia, hypokaliemia, and hypophosphatemia) between groups. The new protocol based on IM administration of insulin lispro preliminarily appears effective and safe for treatment of canine DKA.

Highlights

  • Insulin therapy is the cornerstone of the treatment of diabetic ketoacidosis (DKA)

  • Client-owned dogs with naturally occurring DKA, either newly diagnosed with diabetes mellitus (DM) or with known DM, which were admitted to the Veterinary Teaching Hospital of the Abbreviations: BG, blood glucose; blood β-hydroxybutyrate (BHB), beta-hydroxybutyrate; DKA, diabetic ketoacidosis; DM, diabetes mellitus; IV continuous rate infusion (IVCRI), intravenous continuous rate infusion; LOH, length of hospitalization; NaCl, sodium chloride

  • Eleven cases were managed with IM insulin lispro (Group L) and 13 cases were managed with IVCRI of regular insulin (Group R)

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Summary

Introduction

Insulin therapy is the cornerstone of the treatment of diabetic ketoacidosis (DKA). In the veterinary literature, several protocols based on the use of regular crystalline insulin administered intravenously, intramuscularly or subcutaneously have been described [1,2,3,4]. Rapid-acting analogs (insulin lispro, insulin aspart, and insulin glulisine) are genetically engineered molecules designed to overcome the limitations of regular insulin [10,11,12,13,14,15] Their structure, which differs from the original molecule by one or two amino acids, hinders the hexamerization speeding up their absorption and elimination following SC injection, ensuring a rapid onset and a short duration of hypoglycemic activity [11, 16, 17]. Pharmacodynamic studies in humans have shown that, following SC injection, rapid-acting analogs have an onset of action ranging from 5 to 20 min, and a duration of effect of 2 to 6 h, with peak action occurring between 30 and 90 min [10, 11] These qualities have led to the hypothesis that rapidacting analogs could be successfully used for the management of patients with DKA. The success of insulin analogs has gradually reduced the use of regular insulin (https://investor. lilly.com/financial-information/annual-reports)

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