A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes

Abstract

FOR THE HOE901/4007 STUDY GROUPOBJECTIVE -Insulin glargine (Lantus), a long-acting human insulin analog, provides effective glycemic control when administered at bedtime. This open-label, randomized, parallel group, multicenter study investigated whether insulin glargine is equally effective if administered before breakfast, before dinner, or at bedtime.RESEARCH DESIGN AND METHODS -Patients with type 1 diabetes on basal-bolus therapy (n ϭ 378, 18 -68 years, HbA 1c 5.5-9.8%) were treated with once-daily individually titrated insulin glargine in combination with prandial insulin lispro for 24 weeks.RESULTS -Baseline characteristics were similar in the three groups (overall age 40.9 Ϯ 11.9 years, diabetes duration 17.3 Ϯ 11.5 years). Median total daily insulin dose was similar at baseline (0.65, 0.65, and 0.66 IU/kg for breakfast, dinner, and bedtime, respectively) and remained relatively constant over the study period; however, the insulin glargine-to-total insulin dose ratio increased more in the breakfast group than in the dinner and bedtime groups. A similar reduction of adjusted mean HbA 1c from baseline to end point occurred in all patients (7.6 -7.4, 7.6 -7.5, and 7.6 -7.5% for breakfast, dinner, and bedtime, respectively), and a similar percentage achieved HbA 1c Ͻ7.0% at end point in all groups (29.5, 29.8, and 25.8%, respectively). The 24-h blood glucose profiles in relation to injection time were similar in all groups. The incidences of total symptomatic and severe hypoglycemia did not differ between the three treatment groups; however, nocturnal hypoglycemia occurred in significantly fewer patients in the breakfast group (59.5%) compared with the dinner (71.9%) and bedtime (77.5%) groups (P ϭ 0.005).

How hypoglycaemia can affect the life of a person with diabetes

“…The administration of isophane (NPH) insulin before the evening meal, or the use of soluble insulin with a meal consumed after 20.00 h, predispose to nocturnal hypoglycaemia. Therapeutic changes to diminish this risk include delaying the evening isophane insulin until bedtime, using a fast-acting insulin analogue (insulin lispro or aspart) before a late evening meal [20], or the use of a long-acting insulin analogue (insulin glargine or detemir) as the basal insulin -preferably administered in the morning [21]. The application of continuous subcutaneous insulin infusion (CSII) using an insulin pump, either continuously, or overnight [22] also minimizes the risk of nocturnal hypoglycaemia.…”

Beneficial Effects of Continuous Subcutaneous Insulin Infusion and Flexible Multiple Daily Insulin Regimen Using Insulin Glargine in Type 1 Diabetes

“…However, 1 limitation to our study was bedtime dosing of glargine because a recent study suggested that morning dosing instead would further reduce hypoglycemia frequency. 31 Increased risk of frequent mild to moderate hypoglycemia in individuals with type 1 diabetes is usually associated with high blood glucose variability, low average blood glucose concentration, diabetes of long duration, low BMI, self-reported hypoglycemia unawareness, and vigorous physical activity. 32 In our patients, there was no correlation between hypoglycemia frequency and BMI and/or duration of diabetes.…”

Humaninsulin oder Analoga in der Insulintherapie

“…Vor allem bei morgendlicher Applikation von Insulin glargin besteht ein deutlich geringeres nächt-liches Hypoglykämierisiko [25]. In Einzelfällen kann auch eine 2-mal tägliche Gabe von Insulin glargin zum Erreichen einer stabilen Stoffwechseleinstellung erforderlich sein.…”