IDegLira HIGH Trial
Condition: Diabetes Mellitus
MeSH terms: Diabetes Mellitus
Intervention: IDegLira; Insulin Degludec (U-100); Insulin Aspart
Intervention description: 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.
Intervention MeSH terms: Insulin; Insulin, Globin Zinc; Insulin Aspart; Liraglutide; Insulin, Long-Acting; Xultophy
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
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)
Enrollment: 145.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Type 2 Diabetes

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Type 2 diabetes, diagnosed for ≥ 6 months

          -  HBA1c ≥ 9% - 15%

          -  Previously treated with oral antidiabetic agents, including metformin, sulfonylurea,
             repaglinide/nateglinide, pioglitazone, dipeptidyl peptidase-4 (DPP4), inhibitors,
             SGLT2 inhibitors, (monotherapy + basal insulin) or in combination therapy (2-3
             agents), and/or on basal insulin (neutral protamine hagedorn (NPH), detemir or
             glargine U100) at a total daily dose (TDD) 20-50 units (stable doses of metformin and
             basal insulin for at least 90 days, defined as up to ±10% variability)

          -  Body mass index (BMI) ≤ 45 Kg/m2

        Exclusion Criteria:

          -  Subjects with type 1 diabetes or latent autoimmune diabetes of adults (LADA) (positive
             glutamic acid decarboxylase (GAD-65) antibody and/or ketones)

          -  Subjects with a BG > 400 mg/dL during the screening visit and laboratory evidence of
             diabetic ketoacidosis

          -  Previous treatment with glucagon-like peptide-1 (GLP-1) agonists (during prior 3
             months)

          -  Previous treatment with basal-bolus insulin (within prior 3 months)

          -  Recurrent severe hypoglycemia or known hypoglycemia unawareness.

          -  Personal or family history of medullary thyroid cancer or multiple endocrine neoplasia
             2

          -  Patients with acute or chronic pancreatitis, pancreatic cancer

          -  Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage
             liver disease) or significantly impaired renal function (GFR < 30 ml/min).

          -  Treatment with oral or injectable corticosteroid (equivalent or higher than prednisone
             5 mg/day), parenteral nutrition and immunosuppressive treatment.

          -  Mental condition rendering the subject unable to understand the nature, scope, and
             possible consequences of the study

          -  Hypersensitivity to study drugs

          -  Participating in another investigational drug trial

          -  The receipt of any investigational drug (within 3 months) prior to this trial.

          -  Previously randomized in this trial

          -  Heart Failure New York Heart Association (NYHA) class 4 or uncontrolled hypertension
             (blood pressure > 180/110 mmHg)

          -  Female subjects who are pregnant or breast-feeding at time of enrollment into the
             study

          -  Females of childbearing potential who are not using adequate contraceptive methods (as
             required by local law or practice)

          -  Known or suspected allergy to trial medications (degludec, liraglutide, aspart),
             excipients, or related products.

          -  Subjects could be excluded based on PI's discretion

          -  Unable to comply with trial protocol, and/or at investigator discretion

          -  Patients receiving treatment for active diabetic retinopathy or with proliferative
             retinopathy