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Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial.

Abstract

OBJECTIVE

The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM).

METHODS

This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged > or = 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA1c) value < or = 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA1c) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbA1c value < or = 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines.

RESULTS

Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m2; duration of diabetes, 17.2 [11.4] years; HbA1c, 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA1c did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI, -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA1c were -0.53% and -0.54%. In the 90 patients who completed the trial on once-daily detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA1c were -0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA1c value < or = 7.0% without major hypoglycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 mmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events.

CONCLUSIONS

During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA1c). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    Diabetes Centre, Clinical Sciences Centre, Northern General Hospital, Sheffield, United Kingdom. s.heller@sheffield.ac.uk

    ,

    Source

    Clinical therapeutics 31:10 2009 Oct pg 2086-97

    MeSH

    Adult
    Blood Glucose
    Body Weight
    Diabetes Mellitus, Type 1
    Double-Blind Method
    Endpoint Determination
    Female
    Glycated Hemoglobin A
    Humans
    Hypoglycemia
    Hypoglycemic Agents
    Insulin
    Insulin Detemir
    Insulin Glargine
    Insulin, Long-Acting
    Male
    Middle Aged
    Sample Size
    Treatment Outcome

    Pub Type(s)

    Comparative Study
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    19922879

    Citation

    Heller, Simon, et al. "Comparison of Insulin Detemir and Insulin Glargine in a Basal-bolus Regimen, With Insulin Aspart as the Mealtime Insulin, in Patients With Type 1 Diabetes: a 52-week, Multinational, Randomized, Open-label, Parallel-group, Treat-to-target Noninferiority Trial." Clinical Therapeutics, vol. 31, no. 10, 2009, pp. 2086-97.
    Heller S, Koenen C, Bode B. Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial. Clin Ther. 2009;31(10):2086-97.
    Heller, S., Koenen, C., & Bode, B. (2009). Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial. Clinical Therapeutics, 31(10), pp. 2086-97. doi:10.1016/j.clinthera.2009.10.006.
    Heller S, Koenen C, Bode B. Comparison of Insulin Detemir and Insulin Glargine in a Basal-bolus Regimen, With Insulin Aspart as the Mealtime Insulin, in Patients With Type 1 Diabetes: a 52-week, Multinational, Randomized, Open-label, Parallel-group, Treat-to-target Noninferiority Trial. Clin Ther. 2009;31(10):2086-97. PubMed PMID: 19922879.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Comparison of insulin detemir and insulin glargine in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in patients with type 1 diabetes: a 52-week, multinational, randomized, open-label, parallel-group, treat-to-target noninferiority trial. AU - Heller,Simon, AU - Koenen,Christoph, AU - Bode,Bruce, PY - 2009/08/05/accepted PY - 2009/11/20/entrez PY - 2009/11/20/pubmed PY - 2010/1/27/medline SP - 2086 EP - 97 JF - Clinical therapeutics JO - Clin Ther VL - 31 IS - 10 N2 - OBJECTIVE: The primary study objective was to determine whether insulin detemir (detemir) was noninferior to insulin glargine (glargine) as the basal insulin in a basal-bolus regimen, with insulin aspart as the mealtime insulin, in terms of glycemic control at the end of 52 weeks in patients with type 1 diabetes mellitus (T1DM). METHODS: This multinational, open-label, parallel-group, treat-to-target, noninferiority trial enrolled patients aged > or = 18 years who had had T1DM for at least 12 months, had been taking a basal-bolus insulin regimen for at least 3 months, and had a glycosylated hemoglobin (HbA1c) value < or = 11.0% at screening. Patients were randomized in a 2:1 ratio to receive either detemir or glargine for 52 weeks. The basal insulin was initially administered once daily (in the evening) in both groups; if patients in the detemir group were achieving the plasma glucose (PG) target before breakfast but not before dinner, they were switched to twice-daily administration. Glargine was administered once daily throughout the trial, according to its approved labeling. Each patient attended 13 study visits and received 16 scheduled telephone calls from the trial site. The primary efficacy end point was glycemic control (HbA1c) after 52 weeks of treatment. Secondary end points included the number of patients achieving an HbA1c value < or = 7.0%, with or without a major hypoglycemic episode in the last month of treatment; fasting PG (FPG); within-patient variation in self-monitored plasma glucose (SMPG) before breakfast and dinner; and 10-point SMPG profiles. The noninferiority margin was 0.4%, consistent with US Food and Drug Administration guidelines. RESULTS: Four hundred forty-three patients (mean [SD] age, 42 [12] years; body mass index, 26.5 [4.0] kg/m2; duration of diabetes, 17.2 [11.4] years; HbA1c, 8.1% [1.1%]) received study treatment. After 52 weeks, the estimated mean HbA1c did not differ significantly between the detemir and glargine groups (7.57% and 7.56%, respectively; mean difference, 0.01%; 95% CI, -0.13 to 0.16), consistent with the noninferiority of detemir to glargine. The corresponding estimated changes in HbA1c were -0.53% and -0.54%. In the 90 patients who completed the trial on once-daily detemir and the 173 patients who completed the trial on twice-daily detemir, the estimated changes in HbA1c were -0.49% and -0.58%, respectively. After 52 weeks, there were no significant differences in the proportions of those receiving detemir and glargine who achieved an HbA1c value < or = 7.0% without major hypoglycemia (31.9% and 28.9%, respectively). In addition, there were no significant differences in estimated mean FPG (8.58 and 8.81 mmol/L; mean difference, -0.23 mmol/L; 95% CI, -1.04 to 0.58) or in basal insulin doses. The basal insulin dose was numerically higher in patients receiving detemir twice rather than once daily (0.47 vs 0.33 U/kg, respectively). The relative risks for total and nocturnal hypoglycemia with detemir versus glargine were 0.94 and 1.12, respectively (both, P = NS). Six patients (2.0%) randomized to the detemir group and 4 (2.7%) randomized to the glargine group withdrew due to adverse events. CONCLUSIONS: During 52 weeks of basal-bolus therapy in patients with T1DM, detemir was noninferior to glargine in terms of overall glycemic control (HbA1c). When used according to the approved labeling, detemir and glargine did not differ in tolerability or in terms of the occurrence of hypoglycemia. SN - 1879-114X UR - https://www.unboundmedicine.com/medline/citation/19922879/Comparison_of_insulin_detemir_and_insulin_glargine_in_a_basal_bolus_regimen_with_insulin_aspart_as_the_mealtime_insulin_in_patients_with_type_1_diabetes:_a_52_week_multinational_randomized_open_label_parallel_group_treat_to_target_noninferiority_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0149-2918(09)00363-4 DB - PRIME DP - Unbound Medicine ER -