Glimepiride combined with morning insulin glargine, bedtime neutral protamine hagedorn insulin, or bedtime insulin glargine in patients with type 2 diabetes. A randomized, controlled trial.

Author(s): Fritsche A, Schweitzer MA, Haring HU, 4001 Study Group

Affiliation(s): Medizinische Klinik, Abteilung fur Endokrinologie, Stoffwechsel und Pathobiochemie, Eberhard-Karls-Universitat, Tubingen, Germany.

Publication date & source: 2003-06-17, Ann Intern Med., 138(12):952-9.

Publication type: Clinical Trial; Multicenter Study; Randomized Controlled Trial

BACKGROUND: Patients with type 2 diabetes are often treated with oral antidiabetic agents plus a basal insulin. OBJECTIVE: To investigate the efficacy and safety of glimepiride combined with either morning or bedtime insulin glargine or bedtime neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes. DESIGN: Open-label, randomized, controlled trial. SETTING: 111 centers in 13 European countries. PATIENTS: 695 patients with type 2 diabetes who were previously treated with oral antidiabetic agents. INTERVENTION: Randomization to treatment with morning insulin glargine, bedtime NPH insulin, or bedtime insulin glargine for 24 weeks in addition to 3 mg of glimepiride. The insulin dose was titrated by using a predefined regimen to achieve fasting blood glucose levels of 5.56 mmol/L or lower (< or =100 mg/dL). MEASUREMENTS: Hemoglobin A(1c) values, blood glucose levels, insulin dose, and body weight. RESULTS: Hemoglobin A(1c) levels improved by -1.24% (two-sided 90% CI, -1.10% to -1.38%) with morning insulin glargine, by -0.96% (CI, -0.81% to -1.10%) with bedtime insulin glargine, and by -0.84% (CI, -0.69% to -0.98%) with bedtime NPH insulin. Hemoglobin A(1c) improvement was more pronounced with morning insulin glargine than with NPH insulin (0.40% [CI, 0.23% to 0.58%]; P = 0.001) or bedtime insulin glargine (0.28% [CI, 0.11% to 0.46%]; P = 0.008). Baseline to end-point fasting blood glucose levels improved similarly in all three groups. Nocturnal hypoglycemia was less frequent with morning (39 of 236 patients [17%]) and bedtime insulin glargine (52 of 227 patients [23%]) than with bedtime NPH insulin (89 of 232 patients [38%]) (P < 0.001). CONCLUSION: The risk for nocturnal hypoglycemia was lower with glimepiride in combination with morning and bedtime insulin glargine than with glimepiride in combination with bedtime NPH insulin in patients with type 2 diabetes. Morning insulin glargine provided better glycemic control than did bedtime insulin glargine or bedtime NPH insulin.