Primary outcomeMean· Baseline, Week 26
Change in Hemoglobin A1c (HbA1c)
| Group | Value (percentage of HbA1c) | Spread |
|---|---|---|
| IDegLira | -3.18 | 2.29 |
| Basal-Bolus Insulin | -3.00 | 1.79 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataIDegLira HIGH Trial
NCTNCT03737240 (opens ClinicalTrials.gov in a new tab)Other idIRB00104726
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 145 participants (actual)
- Sponsor
- Emory University · Other
- Design
- Randomized · Open label (no masking)
- Countries
1 country
United States
- Start
- 15 Jan 2019
- Primary completion
- 8 Jul 2022
- Completion
- 8 Jul 2022
- First posted
- 9 Nov 2018
- Last update posted
- 8 Sept 2023
- Conditions
- Diabetes Mellitus
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20192020202120222023
- Ph 3
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
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.
Interventions
- IDegLiraDrug
- Insulin Degludec (U-100)Drug
- Insulin AspartDrug
Arms2
Experimental
IDegLira
Participants in this group will receive IDegLira (with metformin, unless contraindicated) for 26 weeks.
Active comparator
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.
Primary outcomes1
Outcomes the sponsor listed as primary.
Change in Hemoglobin A1c (HbA1c)
Time frame · Baseline, Week 26
Registry description
HbA1c will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Secondary outcomes(20)
Average Fasting Blood Glucose
Time frame · Week1, Week 12, Week 26
Registry description
Mean fasting blood glucose will be compared between study arms. Participants will perform an 8-point, self-monitored blood glucose (SMBG) check by testing their blood sugar at 8 different time points. The measurement taken before breakfast is used to assess fasting blood glucose. For people without diabetes, fasting blood glucose is typically between 70-100 mg/dL while fasting blood glucose for those with diabetes is in the range of 70-130 mg/dL.
Average Daily Blood Glucose
Time frame · Week1, Week 12, Week 26
Registry description
Mean daily blood glucose will be compared between study arms. Participants will perform an 8-point, self-monitored blood glucose (SMBG) check by testing their blood sugar at 8 different time points. Blood glucose levels vary depending on when and what food has been consumed. A blood glucose level taken regardless of timing of meals of greater than 200 mg/dL often indicates diabetes. Blood glucose decreases with improved diabetes management.
Participants With HbA1c <7.0% and no Hypoglycemia
Time frame · Week 26
Registry description
Percent of study participants experiencing HbA1c \<7.0% and no hypoglycemia will be compared between groups. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable. Hypoglycemia is defined as a blood glucose level of \< 70 mg/dL.
Participants With HbA1c <7.0% and no Weight Gain and no Hypoglycemia
Time frame · Week 26
Registry description
Percent of study participants reaching A1c \< 7% without weight gain and no hypoglycemia will be compared between groups. Weight control is typically important in persons with type 2 diabetes and basal-bolus insulin is associated with weight gain. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable. Hypoglycemia is defined as a blood glucose level of \< 70 mg/dL.
Participants With HbA1c <7.5% and no Weight Gain and no Hypoglycemia
Time frame · Week 26
Registry description
Percent of study participants reaching A1c \< 7.5% without weight gain and no hypoglycemia will be compared between groups. Weight control is typically important in persons with type 2 diabetes and basal-bolus insulin is associated with weight gain. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable. Hypoglycemia is defined as a blood glucose level of \< 70 mg/dL.
Participants With HbA1c >10% Achieving HbA1c <7.5%
Time frame · Baseline, Week 26
Registry description
Percent of study participants with baseline HbA1c \>10% reaching A1c \< 7.5% will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Participants With HbA1c >10% Achieving HbA1c <8.0%
Time frame · Baseline, Week 26
Registry description
Percent of study participants with baseline HbA1c \>10% reaching A1c \< 8.0% will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Participants With HbA1c >11% Achieving HbA1c <7.5%
Time frame · Baseline, Week 26
Registry description
Percent of study participants with baseline HbA1c \>11% reaching A1c \< 7.5% will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Participants With HbA1c >11% Achieving HbA1c <8.0%
Time frame · Baseline, Week 26
Registry description
Percent of study participants with baseline HbA1c \>11% reaching A1c \< 8.0% will be compared between study groups. HbA1c measures the average percentage of blood sugar over the past 2 to 3 months and HbA1c can reduce with management of diabetes through diet, exercise, and medication. HbA1c levels below 5.7% are considered normal. Persons with values between 5.7% and 6.4% are considered at high risk of developing diabetes while those with values of 6.5% and above are diagnosed with diabetes. Persons with diabetes aim to get their HbA1c in the range of 7.0 to 7.5% or lower, with below 7.0% being preferable.
Participants With HbA1c <7.0% and no Weight Gain
Time frame · Week 26
Registry description
Percent of study participants reaching A1c \< 7% without weight gain will be compared between groups.
Participants With HbA1c <7.0% and no Hypoglycemia
Time frame · Week 12
Registry description
Percent of study participants reaching A1c \< 7% without hypoglycemia will be compared between groups. Hypoglycemia is defined as a blood glucose level of \< 70 mg/dL.
Number of Participants With Documented Symptomatic Hypoglycemic Events
Time frame · Baseline through Week 26
Registry description
Documented symptomatic hypoglycemia is defined as an event with typical symptoms of hypoglycemia accompanied by SMBG \<70 mg/dL or continuous glucose monitoring (CGM) \< 54 mg/dL that occurs at any time of the day. Number of participants with documented hypoglycemic events will be compared between study groups.
Asymptomatic Hypoglycemic Events
Time frame · Baseline through Week 26
Registry description
Asymptomatic hypoglycemia is defined as no typical symptoms reported by the study participant but detected by SMBG \<70 mg/dL or continuous glucose monitoring (CGM) \< 54 mg/dL. Incidence of asymptomatic hypoglycemic events will be compared between study groups.
Number of Participants With Severe Hypoglycemic Events
Time frame · Baseline through Week 26
Registry description
Severe hypoglycemia is defined as severe cognitive impairment requiring assistance from another person. Number of participants with severe hypoglycemic events will be compared between study groups.
Nocturnal Symptomatic Hypoglycemic Events
Time frame · Baseline through Week 26
Registry description
Nocturnal symptomatic hypoglycemia is defined as an event with typical symptoms of hypoglycemia accompanied by SMBG \<70 mg/dL or continuous glucose monitoring (CGM) \< 54 mg/dL that occurs between midnight and 5:59 am. Incidence of nocturnal symptomatic hypoglycemic events will be compared between study groups.
Nocturnal Asymptomatic Hypoglycemic Events
Time frame · Baseline through Week 26
Registry description
Nocturnal asymptomatic hypoglycemia is defined as SMBG \<70 mg/dL or continuous glucose monitoring (CGM) \< 54 mg/dL between midnight and 5:59 am. Incidence of nocturnal asymptomatic hypoglycemic events will be compared between study groups.
Percentage of Time With Interstitial Glucose <70 mg/dL
Time frame · Baseline through Week 26
Registry description
Percentage of time with a interstitial glucose level below 70 mg/dL as obtained by CGM will be compared between study groups.
Percentage of Time With Interstitial Glucose <54 mg/dL
Time frame · Baseline through Week 26
Registry description
Percentage of time with a interstitial glucose level below \<54 mg/dL as obtained by CGM will be compared between study groups.
Percentage of Time With Interstitial Glucose Between 70 and 180 mg/dL
Time frame · Baseline through Week 26
Registry description
Percentage of time with interstitial glucose in the range of 70-180 mg/dL as measured by CGM will be compared between study groups.
Glycemic Variability
Time frame · Week1, Week 12, Week 26
Registry description
Glycemic variability will be assessed with continuous glucose monitoring (CGM). It will be calculated using CGM and Standard Deviation.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeMean· Week1, Week 12, Week 26
Average Fasting Blood Glucose
| Group | Value (mg/dL) | Spread |
|---|---|---|
| IDegLira | 202.37 | 63.73 |
| Basal-Bolus Insulin | 206.53 | 58.04 |
Secondary outcomeMean· Week1, Week 12, Week 26
Average Daily Blood Glucose
| Group | Value (mg/dL) | Spread |
|---|---|---|
| IDegLira | 220.81 | 64.43 |
| Basal-Bolus Insulin | 225.18 | 65.74 |
Secondary outcomeCount of participants· Week 26
Participants With HbA1c <7.0% and no Hypoglycemia
| Group | Value (Participants) |
|---|---|
| IDegLira | 19 |
| Basal-Bolus Insulin | 6 |
Secondary outcomeCount of participants· Week 26
Participants With HbA1c <7.0% and no Weight Gain and no Hypoglycemia
| Group | Value (Participants) |
|---|---|
| IDegLira | 8 |
| Basal-Bolus Insulin | 1 |
Secondary outcomeNumber· Week 26
Participants With HbA1c <7.5% and no Weight Gain and no Hypoglycemia
| Group | Value (percentage of participants) |
|---|---|
| IDegLira | 19.6 |
| Basal-Bolus Insulin | 5.2 |
Secondary outcomeNumber· Baseline, Week 26
Participants With HbA1c >10% Achieving HbA1c <7.5%
| Group | Value (percentage of participants) |
|---|---|
| IDegLira | 56.8 |
| Basal-Bolus Insulin | 37.5 |
Secondary outcomeNumber· Baseline, Week 26
Participants With HbA1c >10% Achieving HbA1c <8.0%
| Group | Value (percentage of participants) |
|---|---|
| IDegLira | 61.4 |
| Basal-Bolus Insulin | 45.8 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| IDegLiraParticipants in this group will receive IDegLira (with metformin, unless contraindicated) for 26 weeks. 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). | 0 / 72 | 14 / 72 | 30 / 72 |
| Basal-Bolus InsulinParticipants 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. 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. 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. | 0 / 73 | 12 / 73 | 13 / 73 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies0
Studies that cite this trial.
No study cites this trial.
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years up to 80 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
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
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