A Randomized Clinical Trial Comparing Breakfast, Dinner, or Bedtime Administration of Insulin Glargine in Patients With Type 1 Diabetes
- Andreas Hamann, MD1,
- Stephan Matthaei, MD2,
- Christoph Rosak, MD3,
- Louise Silvestre, MD4 and
- for the HOE901/4007 Study Group
- 1Division of Endocrinology and Metabolism, Department of Medicine, University Hospital Heidelberg, Heidelberg, Germany
- 2Department of Medicine, Division of Endocrinology and Metabolism, University of Tübingen, Tübingen, Germany
- 3Department of Diabetology and Metabolic Disorders, C.V. Noorden Klinik, Krankenhaus Sachsenhausen, Frankfurt, Germany
- 4Aventis Pharma R&D 102, Romainville, France
OBJECTIVE—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 = 378, 18–68 years, HbA1c 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 ± 11.9 years, diabetes duration 17.3 ± 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 HbA1c 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 HbA1c <7.0% 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 = 0.005).
CONCLUSIONS—These data suggest that insulin glargine, in combination with insulin lispro, is safe and effective when administered before breakfast, before dinner, or at bedtime.
Address correspondence and reprint requests to Andreas Hamann, MD, Division of Endocrinology and Metabolism, Department of Medicine, University Hospital Heidelberg, Bergheimer Str. 58, D-69115 Heidelberg, Germany. E-mail:.
Received for publication 20 December 2002 and accepted in revised form 7 March 2003.
A.H. has received honoraria for speaking engagements from Abbott, Aventis, GlaxoSmithKline, Pfizer, Roche, and Takeda and is a paid consultant for GlaxoSmithKline and Takeda. A.H. has received research support from Astra Zeneca, Aventis, GlaxoSmithKline, Janssen-Cilag, Novartis, Novo Nordisk, Pfizer, Roche, and Takeda. S.M. has received honoraria for speaking engagements from Aventis, Bayer, GlaxoSmithKline, Lilly, Merck, Novartis, Novo Nordisk, and Takeda and has received grant support from Aventis, Bayer, Merck, and Novo Nordisk. C.R. served on the advisory board of GlaxoSmithKline Munich; has delivered lectures for Aventis, Lilly, Novo Nordisk, Bayer, and Merck; and has received a research grant from Aventis.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE