IDegLira HIGH Trial
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Study type: Interventional
Phase: Phase 3

Summary: 
      Basal-bolus insulin therapy is recommended for patients with poorly controlled type 2
      diabetes (T2D) and HbA1c >9%. However, basal-bolus insulin is labor intensive and associated
      with increased risk of hypoglycemia, glycemic variability, weight gain and poor compliance.
      Thus, there is a critical need for a simpler treatment regimen that could overcome these
      limitations. IDegLira, a fixed-ratio combination (FRC) therapy consisting of insulin degludec
      and liraglutide, is an attractive option for this population given its proven benefits on
      glycemic control, weight and compliance. This study aims to show that a simpler regimen using
      a novel FRC agent (IDegLira) can improve glycemic control, decrease hypoglycemia, reduce the
      burden of diabetes care, and improve satisfaction/adherence in patients with poorly
      controlled T2D with HbA1c between ≥ 9-12%. This open-label, treat-to- target, two-arm
      parallel, controlled trial will randomize participants with T2D and HbA1c ≥ 9%, treated with
      oral anti-diabetic agents and/or basal insulin therapy to lDegLira or basal-bolus insulin for
      26 weeks.
    

Detailed description: 
      Extensive literature has shown that persistent hyperglycemia is associated with short- and
      long-term complications. Sustained hyperglycemia, also known as glucotoxicity, leads to
      progressive loss of beta-cell function and is considered a key pathophysiological process in
      the development of type 2 diabetes (T2D). Patients with severe hyperglycemia may respond
      poorly to oral anti-diabetic agents (OAD) alone initially and frequently require insulin to
      achieve glycemic targets. Current guidelines recommend to initiate therapy with basal insulin
      and progressively step up to basal-bolus insulin in patients with high HbA1c >9%,
      particularly if symptomatic or with catabolic symptoms.

      A basal-bolus insulin regimen increases the risk of hypoglycemia, weight gain and glycemic
      variability, which are limiting factors in achieving glycemic targets. A basal-bolus insulin
      regimen is also labor intensive and often requires multiple daily injections, further
      increasing the burden of diabetes care and decreasing patient adherence. In contrast,
      simplified treatment plans may improve adherence, leading to glycemic targets achievement.
      Thus, there is a critical need for simpler regimens that could overcome clinical inertia,
      improve patient adherence, and decrease glycemic variability in patients with poorly
      controlled type 2 diabetes. This prospective randomized control trial will compare IDegLira
      to basal-bolus insulin regimen in achieving glycemic control, while reducing hypoglycemia,
      glycemic variability, and weight gain in patients with uncontrolled T2D and HbA1c ≥9%.
    

Intervention name(s): IDegLira; Insulin Degludec (U-100); Insulin Aspart
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Participants in this study arm will discontinue all other diabetes medications, except for metformin which will be continued at prescribed dose (unless contraindicated). IDegLira will be given once daily, at the same time of the day with or without food for 26 weeks. IDegLira will be titrated until the maximum dose is reached, up to the target fasting blood glucose of 70 to 100 milligrams per deciliter (mg/dL).; Participants in the basal-bolus insulin study arm will discontinue all other diabetes medications, except for metformin which will be continued at the prescribed dose (unless contraindicated). Insulin Degludec (U-100) will be given once daily at the same time for 26 weeks. The dose will be titrated up to the fasting blood glucose target of 70 to 100 mg/dL, with no maximum dose.; Participants in the basal-bolus insulin study arm will discontinue all other diabetes medications, except for metformin which will be continued at the prescribed dose (unless contraindicated). Insulin aspart will be taken before meals with a titration schedule and dose adjustment protocol to target pre-meal blood glucose level of 70 to 100 mg/dL.
Other intervention name(s): Xultophy 100/3.6; insulin degludec; liraglutide; Tresiba FlexTouch; NovoLog
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Liraglutide; Insulin, Long-Acting; Xultophy
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized in a 1 to 1 ratio to receive the study treatment or standard of care.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Type 2 Diabetes