A Randomized Controlled Trial Comparing the Safety and Efficacy of IDegLira Versus Basal Bolus in Patients With Poorly Controlled Type 2 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 145
- 试验地点
- 2
- 主要终点
- Change in Hemoglobin A1c (HbA1c)
研究概览
简要总结
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.
详细描述
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%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
IDegLira
Participants in this group will receive IDegLira (with metformin, unless contraindicated) for 26 weeks.
干预措施: IDegLira (Drug)
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.
干预措施: Insulin Degludec (U-100) (Drug)
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.
干预措施: Insulin Aspart (Drug)
结局指标
主要结局
Change in Hemoglobin A1c (HbA1c)
时间窗: Baseline, Week 26
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.
次要结局
- Participants With HbA1c <7.5% and no Weight Gain and no Hypoglycemia(Week 26)
- Percentage of Time With Interstitial Glucose <70 mg/dL(Baseline through Week 26)
- Participants With HbA1c <7.0% and no Hypoglycemia(Week 12)
- Participants With HbA1c >10% Achieving HbA1c <7.5%(Baseline, Week 26)
- Participants With HbA1c >10% Achieving HbA1c <8.0%(Baseline, Week 26)
- Participants With HbA1c <7.0% and no Weight Gain(Week 26)
- Average Fasting Blood Glucose(Week1, Week 12, Week 26)
- Participants With HbA1c >11% Achieving HbA1c <8.0%(Baseline, Week 26)
- Asymptomatic Hypoglycemic Events(Baseline through Week 26)
- Nocturnal Symptomatic Hypoglycemic Events(Baseline through Week 26)
- Percentage of Time With Interstitial Glucose <54 mg/dL(Baseline through Week 26)
- Glycemic Variability(Week1, Week 12, Week 26)
- Diabetes Treatment Satisfaction Questionnaire - Change (DTSQc) Score(Week 26)
- Nocturnal Asymptomatic Hypoglycemic Events(Baseline through Week 26)
- Average Daily Blood Glucose(Week1, Week 12, Week 26)
- Participants With HbA1c <7.0% and no Weight Gain and no Hypoglycemia(Week 26)
- Participants With HbA1c >11% Achieving HbA1c <7.5%(Baseline, Week 26)
- Number of Participants With Documented Symptomatic Hypoglycemic Events(Baseline through Week 26)
- Percentage of Time With Interstitial Glucose Between 70 and 180 mg/dL(Baseline through Week 26)
- Diabetes Treatment Satisfaction Questionnaire - Status (DTSQs) Score(Baseline, Week 12)
- Total Daily Insulin Dose(Baseline, Week 26)
- Number of Participants With Severe Hypoglycemic Events(Baseline through Week 26)
- Treatment-Related Impact Measures for Diabetes (TRIM-D) Survey Score(Baseline, Week 12, Week 26)
- Number of Emergency Room (ER) Visits(Baseline through Week 26)
- Number of Hospital Readmissions(Baseline through Week 26)
研究者
Rodolfo Galindo
Assistant Professor
Emory University