INITIATE study shows improved blood glucose-lowering effect of NovoLog Mix 70/30 compared to Lantus


New data from head-to-head studies may encourage clinicians to rethink current approaches to initiating insulin in type 2 diabetes

Novolog® Mix 70/30 (70% insulin aspart protamine suspension and 30% insulin aspart injection, [rDNA origin]), a dual-action insulin analog that does not contain NPH insulin, is more effective in helping patients initiating insulin therapy achieve control of their blood glucose levels compared to insulin glargine, according to data from the INITIATE (INITiation of Insulin to reach A1c TargEt) study presented today at the 64th annual meeting of the American Diabetes Association (ADA) in Orlando, Florida.

"This study illustrates the value of initiating insulin therapy with a dual-acting insulin analog that provides a physiological approach to controlling insulin needs at mealtime and throughout the day," commented the study's lead investigator Philip Raskin, M.D., Professor of Medicine, University of Texas Southwestern Medical Center, Dallas. "The results of this study should encourage clinicians to reexamine their approach to helping diabetes patients transition to insulin therapy."

INITIATE key findings

INITIATE evaluated insulin-nave patients whose blood glucose levels were not being adequately controlled with oral diabetes medications (A1C levels > 8%). At the end of 28 weeks, the study showed that 66 percent of patients taking NovoLog® Mix 70/30 reached target A1C levels of 7.0 percent compared to 40 percent taking insulin glargine. Indeed, 42 percent of individuals on NovoLog® Mix 70/30 achieved an A1C of equal to or less than 6.5 percent compared to 28 percent receiving glargine. Mean A1C reduction was 0.43 percent point lower in the NovoLog Mix 70/30 group versus the insulin glargine group (-2.79 vs. 2.36 A1C reduction, p<0.01).

Major findings of INITIATE include:

Lowering A1C levels

  • Average A1C value (the measurement of a person's blood glucose level over the preceding two to three months) in the NovoLog® Mix 70/30 group was significantly lower than in the insulin glargine group after 28 weeks for the 233 patients enrolled in the study (6.9 percent vs. 7.4 percent, p=0.001).
  • A greater percentage of patients taking NovoLog® Mix 70/30 compared to insulin glargine-treated patients reached the recommended target A1C values of 6.5 percent (42 percent vs. 28 percent) and 7.0 percent (66 percent vs. 40 percent).

    Post-mealtime blood glucose control

  • Patients taking NovoLog® Mix 70/30 demonstrated significantly greater control of post-mealtime glucose increment above pre-meal glucose levels compared to insulin glargine at breakfast (33.9 mg/dL vs. 55.3 mg/dL, p<0.01) and dinner (19.0 mg/dL vs. 41.8 mg/dL, p<0.05). This resulted in a significantly lower mean blood glucose increment averaged over three meals (32.5mg/dL vs. 43.2 mg/dL, p<0.05).

    INITIATE trial design

    In the 28-week, open-label, parallel-group study, patients took NovoLog® Mix 70/30, a dual-action insulin analog that combines in one injection fast-acting (bolus) insulin for control of postprandial (after meals) plasma glucose levels (PPG) and intermediate-acting (basal) insulin for control of fasting plasma glucose (FPG) levels, before breakfast and dinner. Patients taking insulin glargine, a basal-only insulin product, received treatments at bedtime. Both study arms received metformin, an oral diabetes medication.

    In the study, hypoglycemic events were the most common side effect reported in both groups. Major hypoglycemic events were rare, with no major events reported in the NovoLog® Mix 70/30 group and one observed in the insulin glargine group. Minor hypoglycemic events occurred more frequently with NovoLog® Mix 70/30 compared to insulin glargine.

    Additional research confirms INITIATE results

    A separate study comparing the pharmacokinetic (PK) and pharmacodynamic (PD) properties of the two diabetes treatments also found that NovoLog® Mix 70/30 had a greater glucose-lowering effect in patients with type 2 diabetes compared to an equivalent dosage of insulin glargine.

    On two occasions approximately one week apart, 12 insulin-nave male patients with type 2 diabetes were administered equal doses of either NovoLog® Mix 70/30 (split dose injected at 8 a.m. and 8 p.m.) or insulin glargine (administered as a single dose at 8 a.m.) after an overnight fast. Glucose was infused to maintain blood glucose levels. In patients treated with NovoLog® Mix 70/30, glucose infusion rates rose more rapidly and reached a higher peak compared to insulin glargine and overall plasma insulin was also significantly greater, resulting in a 32 percent greater glucose infusion to maintain glucose levels with NovoLog® Mix 70/30. Additionally, suppression of endogenous insulin secretion (insulin produced by the pancreas) was 14 percent lower with NovoLog® Mix 70/30 than insulin glargine.

    Effectiveness of once-daily NovoLog® Mix 70/30

    In other data presented at the ADA, 23 percent of patients taking once-daily NovoLog Mix 70/30 achieved target A1C =6.5 percent, and 42 percent reached A1C <7.0 percent, when added to oral antidiabetic therapy in type 2 diabetes patients whose blood glucose levels were not being adequately controlled with oral diabetes medications and/or basal insulin.

    "This research demonstrates that once-daily therapy with NovoLog® Mix 70/30 is a reasonable option to help transition patients to insulin therapy and achieve recommended blood glucose targets," said study author Rajeev Jain, M.D., an endocrinologist at the Milwaukee Medical Clinic in Wisconsin.

    About NovoLog® Mix 70/30

    NovoLog® Mix 70/30 is indicated for the treatment of patients with diabetes mellitus for the control of hyperglycemia. Because NovoLog® Mix 70/30 has peak pharmacodynamic activity one hour after injection, it should be administered with meals. NovoLog® Mix 70/30 is contraindicated during episodes of hypoglycemia and in patients hypersensitive to NovoLog® Mix 70/30 or one of its excipients. Hypoglycemia is the most common adverse effect of insulin therapy, including NovoLog® Mix 70/30.

    Any change in insulin should be made cautiously and only under medical supervision.

    Source: Eurekalert & others

    Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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