Insulin analogs versus human insulin in the treatment of patients with diabetic ketoacidosis: a randomized controlled trial

Abstract

Objective: To compare the safety and efficacy of insulin analogs and human insulins both during acute intravenous treatment and during the transition to subcutaneous insulin in patients with diabetic ketoacidosis (DKA).

Research design and methods: In a controlled multicenter and open-label trial, we randomly assigned patients with DKA to receive intravenous treatment with regular or glulisine insulin until resolution of DKA. After resolution of ketoacidosis, patients treated with intravenous regular insulin were transitioned to subcutaneous NPH and regular insulin twice daily (n = 34). Patients treated with intravenous glulisine insulin were transitioned to subcutaneous glargine once daily and glulisine before meals (n = 34).

Results: There were no differences in the mean duration of treatment or in the amount of insulin infusion until resolution of DKA between intravenous treatment with regular and glulisine insulin. After transition to subcutaneous insulin, there were no differences in mean daily blood glucose levels, but patients treated with NPH and regular insulin had a higher rate of hypoglycemia (blood glucose <70 mg/dl). Fourteen patients (41%) treated with NPH and regular insulin had 26 episodes of hypoglycemia and 5 patients (15%) in the glargine and glulisine group had 8 episodes of hypoglycemia (P = 0.03).

Conclusions: Regular and glulisine insulin are equally effective during the acute treatment of DKA. A transition to subcutaneous glargine and glulisine after resolution of DKA resulted in similar glycemic control but in a lower rate of hypoglycemia than with NPH and regular insulin. Thus, a basal bolus regimen with glargine and glulisine is safer and should be preferred over NPH and regular insulin after the resolution of DKA.

Trial registration: ClinicalTrials.gov NCT00596687.

Figure 1

Changes in metabolic profile in patients with DKA treated with intravenous glulisine (○) and regular insulin (●). To convert the values for glucose from milligrams per deciliter to millimoles per liter, multiply by 0.05551. A: glucose; B: pH; C: bicarbonate; D: anion gap.