Clinical trial NCT03737240: IDegLira HIGH Trial
Official title: A Randomized Controlled Trial Comparing the Safety and Efficacy of IDegLira Versus Basal Bolus in Patients With Poorly Controlled Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus
Keywords: Type 2 Diabetes
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2018-11-09
Enrollment: 145
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized in a 1 to 1 ratio to receive the study treatment or standard of care.
Primary purpose: TREATMENT

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%.

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

Primary outcomes:
measure: Change in Hemoglobin A1c (HbA1c)
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Average Fasting Blood Glucose
timeFrame: Week1, Week 12, Week 26
measure: Average Daily Blood Glucose
timeFrame: Week1, Week 12, Week 26
measure: Participants With HbA1c <7.0% and no Hypoglycemia
timeFrame: Week 26
measure: Participants With HbA1c <7.0% and no Weight Gain and no Hypoglycemia
timeFrame: Week 26
measure: Participants With HbA1c <7.5% and no Weight Gain and no Hypoglycemia
timeFrame: Week 26
measure: Participants With HbA1c >10% Achieving HbA1c <7.5%
timeFrame: Baseline, Week 26
measure: Participants With HbA1c >10% Achieving HbA1c <8.0%
timeFrame: Baseline, Week 26
measure: Participants With HbA1c >11% Achieving HbA1c <7.5%
timeFrame: Baseline, Week 26
measure: Participants With HbA1c >11% Achieving HbA1c <8.0%
timeFrame: Baseline, Week 26
measure: Participants With HbA1c <7.0% and no Weight Gain
timeFrame: Week 26
measure: Participants With HbA1c <7.0% and no Hypoglycemia
timeFrame: Week 12
measure: Number of Participants With Documented Symptomatic Hypoglycemic Events
timeFrame: Baseline through Week 26
measure: Asymptomatic Hypoglycemic Events
timeFrame: Baseline through Week 26
measure: Number of Participants With Severe Hypoglycemic Events
timeFrame: Baseline through Week 26
measure: Nocturnal Symptomatic Hypoglycemic Events
timeFrame: Baseline through Week 26
measure: Nocturnal Asymptomatic Hypoglycemic Events
timeFrame: Baseline through Week 26
measure: Percentage of Time With Interstitial Glucose <70 mg/dL
timeFrame: Baseline through Week 26
measure: Percentage of Time With Interstitial Glucose <54 mg/dL
timeFrame: Baseline through Week 26
measure: Percentage of Time With Interstitial Glucose Between 70 and 180 mg/dL
timeFrame: Baseline through Week 26
measure: Glycemic Variability
timeFrame: Week1, Week 12, Week 26
measure: Diabetes Treatment Satisfaction Questionnaire - Status (DTSQs) Score
timeFrame: Baseline, Week 12
measure: Diabetes Treatment Satisfaction Questionnaire - Change (DTSQc) Score
timeFrame: Week 26
measure: Treatment-Related Impact Measures for Diabetes (TRIM-D) Survey Score
timeFrame: Baseline, Week 12, Week 26
measure: Number of Emergency Room (ER) Visits
timeFrame: Baseline through Week 26
measure: Number of Hospital Readmissions
timeFrame: Baseline through Week 26
measure: Total Daily Insulin Dose
timeFrame: Baseline, Week 26
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Health System
state: Georgia
city: Atlanta
country: United States
facility: Emory Clinic
state: Georgia
Study officials:
affiliation: Emory University
name: Rodolfo Galindo, MD
role: PRINCIPAL_INVESTIGATOR
References: