IDegLira HIGH Trial

NCT ID: NCT03737240

Last Updated: 2023-09-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 145 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-01-15
• Study Completion Date: 2022-07-08

Brief 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%.

Conditions

Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

IDegLira

Participants in this group will receive IDegLira (with metformin, unless contraindicated) for 26 weeks.

Group Type: EXPERIMENTAL

IDegLira

Intervention Type: DRUG

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).

Basal-Bolus Insulin

Participants in this group will receive basal-bolus insulin (with metformin, unless contraindicated) for 26 weeks. The basal-bolus insulin regimen includes Insulin Degludec (U-100) and Insulin Aspart.

Group Type: ACTIVE_COMPARATOR

Insulin Degludec (U-100)

Intervention Type: DRUG

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.

Insulin Aspart

Intervention Type: DRUG

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.

Interventions

IDegLira

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).

Intervention Type: DRUG

Insulin Degludec (U-100)

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.

Intervention Type: DRUG

Insulin Aspart

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 Type: DRUG

Other Intervention Names

Xultophy 100/3.6; insulin degludec; liraglutide; Tresiba FlexTouch; NovoLog

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novo Nordisk A/S

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Rodolfo Galindo

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rodolfo Galindo, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Locations

Grady Health System

Atlanta, Georgia, United States

Emory Clinic

Atlanta, Georgia, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

IRB00104726

Identifier Type: -

Identifier Source: org_study_id