Improved glycemic control without an increase in severe hypoglycemic episodes in intensively treated patients with type 1 diabetes receiving morning, evening, or split dose insulin glargine

Abstract

Objective: To see if insulin glargine improves glycemic control in a clinical setting. Research design and methods: A questionnaire and electronic database were used to assess glycemic parameters for 292 type 1 diabetic subjects taking ≥4 injections per day and receiving glargine as their only long-acting basal insulin for at least 6 months. Sixty-three subjects were taking glargine in the morning, 125 were taking glargine in the evening, and 104 were splitting the glargine dose between the morning and evening. Results: The mean (±S.D.) age and duration of diabetes were 32±10 years and 15.9±10.3 years, respectively. The mean (±S.E.M.) durations of treatment with glargine were 13.1±0.6 months, 12.2±0.4 months, and 14.3±0.5 months for the morning, evening, and split treatment groups, respectively (P<0.01). The A1C values improved significantly from baseline for the evening and the split dosage groups or when all groups were combined. The mean basal insulin dose was significantly reduced at the end of the study in all the three groups from baseline with no change in the short-acting insulin dose. The number of severe hypoglycemic episodes decreased from 379 in the year prior to glargine treatment to 167 in the post-glargine year. The weight gain was significantly higher in the group that took the split glargine dose (P<0.01). Conclusions: Similar or improved glycemic control was achieved by administering glargine in the morning, evening, or using a split dose without any further increase in severe hypoglycemic episodes. Splitting the glargine dose did not offer any advantages in glycemic control parameters.

Introduction

Several prospective studies have shown the importance of improving glycemic control to reduce the risk for microvascular complications both in people with type 1 [1] and type 2 [2], [3] diabetes. The intensive treatment groups in all of these studies had reduced microvascular complications but increased their risk for severe hypoglycemic episodes.

New insulin analogues, beginning with insulin lispro (Humalog^®), have resulted in improved glycemic control without an increase in severe hypoglycemic events [4], [5], [6]. The pharmacokinetics and pharmacodynamics of the short-acting insulins, insulin lispro [7] and more recently insulin aspart (Novolog^®) [8], have been shown to be closer to physiologic insulin secretion for the post-prandial state with rapid onset of action [7], [8] and a peak effect at approximately 1 h [4], [6]. The short-acting analog usage has significantly reduced hypoglycemia especially at night when compared to human regular insulin. All the studies on new short-acting analogs, in the past, included using intermediate-acting insulins, e.g. NPH and/or Ultralente [4], [5], [6], [7], [8].

The use of intermediate-acting insulins NPH and Ultralente as basal insulins have several limitations that include: (1) large inter- and intra-individual variations due to the presence of excipients that need to be properly re-suspended [9], [10]; (2) peak effect at approximately 4–6 h; and (3) hypoglycemia after 4–6 h due to undesired peak effect and thus need of a mid-morning and/or mid-afternoon snack resulting in weight gain. More recently, a new basal insulin, insulin glargine (Lantus^®), has become available which more closely simulates normal human basal insulin secretion. It has a 24-h basal insulin profile with almost no peak in activity [9], [10]. Although there have been prospective research studies of insulin glargine documenting its safety and efficacy [9], [10], [11], [12], [13], [14], [15], there are no reports of its use in a “real-life” clinic setting. There are also no reports comparing morning, evening, and split dosage (morning and evening) injections of glargine.

The purpose of this investigator-initiated report was to determine the efficacy of morning, evening, or morning plus evening split injections of insulin glargine in adult patients with type 1 diabetes in a general diabetes outpatient clinical setting.