Subcutaneous Lispro Insulin for Diabetic Ketoacidosis

Abstract & Commentary

Source: Umpierrez GE, et al. Efficacy of subcutaneous insulin lispro vs. continuous intravenous regular insulin for the treatment of patients with diabetic ketoacidosis. Am J Med 2004; 117: 291-296.

The standard of care for the treatment of diabetic ketoacidosis (DKA) is hospitalization for administration of regular insulin by continuous intravenous (IV) infusion. Patient monitoring is time- and labor-intensive, and inadvertent hypoglycemia is a recognized complication. In the majority of hospitals, therefore, patients being treated for DKA are admitted to the intensive care unit (ICU) until their hyperglycemia and ketonemia have resolved.

Insulin lispro is an analog of human insulin with a more rapid onset than regular insulin (10-20 min vs 1-2 hr). Insulin lispro also has a faster time to peak activity than regular insulin (about 1 hr vs about 3 hr) and shorter duration of activity. The authors of this study proposed that patients with DKA could be treated safely in a non-ICU setting using repeated subcutaneous (SQ) doses of insulin lispro, and performed a study comparing this treatment regimen with standard regular insulin therapy administered by continuous IV infusion within the ICU setting.

Patients qualified for the study if they presented to the ED with DKA and were not critically ill. They were randomized to receive therapy with either insulin lispro SQ (lispro group) or regular insulin by IV (regular group). Those in the lispro group were admitted to a general medicine ward or intermediate care unit and received a 0.3 unit/kg SQ injection, followed by an hourly 0.1 U/kg injection. Patients in the regular insulin group received an initial bolus of 0.1 U/kg, followed by a continuous infusion at 0.1 U/kg/hr. Blood glucose levels were checked hourly in the lispro group and every 2 hours in the regular group; serum chemistry was checked every 2 hours initially, then every 4 hours. The endpoint was resolution of hyperglycemia and ketoacidosis.

Twenty patients were enrolled in each study group. There were no intergroup differences in time to correction of hyperglycemia (7 hours in each group) or time to correction of ketoacidosis (10-11 hours). There were also no differences in rates of hypoglycemic events (one patient in each group) or length of hospital stay. Hospital charges were substantially greater for patients in the regular insulin group, who were, by design, admitted to the ICU. The authors conclude that DKA can be safely and economically treated in non-ICU settings using insulin lispro SQ rather than regular insulin IV.

Commentary by David J. Karras, MD, FAAEM, FACEP

The value of this study lies in demonstrating the feasibility of treating patients with DKA with SQ injections of fast-acting insulin analogs. By virtue of their rapid onset and shorter half-lives, repeated SQ doses may be used to titrate the blood glucose levels with a low risk of bottoming-out the blood sugar. Thus, these analogs may be appropriate for frequent administration in a non-ICU setting. The authors demonstrate that therapy with SQ insulin lispro resolves DKA as quickly and safely as therapy with IV regular insulin.

The cost savings demonstrated by the study is actually an artifact of the study design. By protocol, ICU admission was mandated for the regular insulin group, while the lispro group was admitted to a regular ward or intermediate care unit. The lower cost of treatment associated with lispro therapy resulted from the higher cost of the ICU stay itself and the comparison is not valid. Also by design, the lispro group actually received more frequent blood glucose checks than the regular insulin group. This might suggest a higher cost of therapy associated with lispro had the patients been treated in comparable settings, but again, this is an artifact of study design. In short, the authors cannot render conclusions regarding cost-effectiveness of insulin lispro therapy.

A more persuasive conclusion, entirely justified by the study, is that stable patients with DKA routinely do not require ICU admission, even if they receive regular insulin by continuous IV infusion. I suspect that a shift in the treatment setting would result in far greater cost savings than a change in the type of insulin or method of delivery.

Dr. Karras, Associate Professor of Emergency Medicine, Associate Chair for Academic Affairs, and Research Director, Department of Emergency Medicine, Temple University School of Medicine, Philadelphia, PA, is on the Editorial Board of Emergency Medicine Alert.