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The Liraglutide Effect & Action in Diabetes

Liraglutide Effect and Action in Diabetes (LEAD) is a series of trials that study the effect of the diabetes medication liraglutide by itself (monotherapy) and with other oral diabetes medications. Liraglutide has the brand name Victoza.

  1. Liraglutide Medication

    • Liraglutide is a once-daily, GLP-1 injectable diabetes medication that targets beta-cells, providing a reduction in hemoglobin A1C. Hemoglobin A1C, or A1C, is a laboratory test that measures the average amount of blood sugar on red blood cells for a 90-day period. This indicates a person's average blood sugar level for the past three months. The target A1C for people with diabetes is less than 7 percent. As A1C levels rise above this level, the result is a significant increase in health complications.

    Gut Hormones

    • GLP-1 is a hormone produced in the intestines that causes an increase in the amount of insulin released after eating. Insulin is produced in the beta cells of the pancreas. The secretion of GLP-1 is dependent on the presence of nutrients in the small intestine. It has a half-life of less than two minutes, meaning half of the effect of GLP-1 is gone within about two minutes of its secretion. It is rapidly degraded by the enzyme DPP-4.

      DPP-4 (dipeptidyl peptidase-4) is an enzyme expressed on the surface of most cell types. It plays a major role in glucose metabolism and degrades the GLP-1 hormone. It is also associated with immune regulation, signal transduction and apoptosis (prevention of beta cell decay).

    LEAD Trials Overview

    • Six LEAD trials assess the efficacy and safety of liraglutide in patients with type 2 diabetes. It is evaluated with Metformin, the sulfonylurea (SU) glimepiride, Metformin + TZD (rosiglitazone) and Metformin + SU, and compared to exenatide and insulin glargine.

      LEAD 1 trial included liraglutide + SU vs. TZD + SU. LEAD 2 trial included liraglutide + Metformin vs. SU + Metformin. LEAD 3 trial was for liraglutide monotherapy vs. SU. LEAD 4 trial used liraglutide + Metformin + TZD vs Metformin + TZD. LEAD 5 trial included liraglutide + SU + Metformin vs. glargine + SU + Metformin. LEAD 6 trial included liraglutide + Metformin and/or SU vs. exenatide + Metformin and/or SU.

    Baseline Patient Characteristics

    • For each trial, the following characteristics of patients apply: The average age is mid-50s; average duration of diabetes is 5 to 10 years; average A1C is 8.1 to 8.6 percent; and average body mass index (BMI) is 30 to 34kg/m2.

    Trial Conclusions

    • In all of the LEAD trial studies, significantly more patients in the liraglutide groups achieved the American Diabetes Association target A1C of less than 7 percent vs. comparators. Patients using liraglutide had an increase in beta-cell function (based on some parameters), a decrease in body weight (with the exception of LEAD 1) and a reduction in systolic blood pressure (results varied in each trial). Efficacy measures were achieved with a low rate of minor hypoglycemia in all LEAD studies.

    Safety/Tolerability

    • Liraglutide therapy has a low risk of hypoglycemia. Relatively few patients withdrew from the LEAD studies due to adverse events, but the majority of withdrawals were due to side effects such as nausea, diarrhea and vomiting.

    Liraglutide and Blood Sugar Control

    • Based on LEAD studies, liraglutide may be a treatment option for people with type 2 diabetes that is not controlled by Metformin alone. Type 2 diabetics may contact their physician for further information and discussion regarding using the medication to achieve an A1C goal.

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