Combination Therapy With Semaglutide, Empagliflozin and Pioglitazone Versus Standard Therapy in Newly Diagnosed Type 2 Diabetes: a Multi-center Randomized Controlled Trial
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 296
- 试验地点
- 1
- 主要终点
- Diabetic remission rate
研究概览
简要总结
The goal of this clinical trial is to learn the efficany of combination therapy with semaglutide, empagliflozin and pioglitazone versus standard therapy in newly diagnosed type 2 diabetes. The main objectives to achieve are:
- To compare efficacy of the triple combination therapy against standard therapy in achieving type 2 diabetes remission in patients newly diagnosed with T2DM.
- To compare the effects on β-cell function and glycemic control of the triple combination therapy against standard therapy in patients newly diagnosed with T2DM
Researchers will compare drug new triple combination therapy with semaglutide, empagliflozin, and pioglitazone to standard therapy (metformin-based treatment) to see if new triple combination therapy works better in achieving type 2 diabetes remission .
Participants will:
- Take new triple combination therapy or a standard therapy every day for 6 months
- Visit the clinic once every 0.5-1 month for checkups and tests
- Keep a diary of their fingertip blood glucose and adverse events
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18 years≤age≤75 years at the time of signing informed consent.
- •Newly diagnosed with type 2 diabetes, or diagnosed within 1 years according to the WHO diagnostic criteria.
- •Individuals who had not received previous antidiabetic therapy, or had not received antidiabetic therapy within 3 months prior to screening, or had not received antidiabetic therapy for more than 3 consecutive months or a combined total of more than 3 months in the past 2 years.
- •6.5%≤HbA1c≤9.0% at screening confirmed by central laboratory analysis.
- •BMI≥24 kg/m2.
排除标准
- •Individuals with type 1 diabetes or special types of diabetes.
- •Allergy or intolerance to investigational drugs.
- •Estimated Glomerular Filtration Rate (eGFR) <20 mL/min/1.73 m².
- •Individuals with heart failure in New York Heart Association [NYHA] class III or IV in the 6 months prior to randomization.
- •History of bladder cancer or hematuria.
- •History of Multiple Endocrine Neoplasia Type 2 (MEN 2) or relevant family history.
- •History or family history of Medullary Thyroid Carcinoma (MTC), or susceptibility to MTC due to hereditary conditions.
- •History of fasting blood glucose≥13.9 mmol/L or the necessity for insulin use due to severe infection, diabetic foot, etc.
- •History of acute diabetic complications: including diabetic ketoacidosis, hyperglycemic hyperosmolar state, lactic acidosis.
- •Severe diabetic microvascular complications: proliferative retinopathy, or urinary AER>300mg/g, or urinary protein positive, quantitative >0.5g/24h.
- •Uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy.
- •Severe diabetic macrovascular complications: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischemic attack and/or peripheral arterial disease required for vascular intervention or amputation within the 12 months prior to screening.
- •Blood pressure persistently higher than 180/110 mmHg and not controllable to ≤160/100 mmHg within 1 week.
- •Alanine Aminotransferase (ALT) ≥2.5 times the upper normal limit, total bilirubin ≥1.5 times the upper normal limit.
- •Hemoglobin <100g/L or requiring regular blood transfusion.
- •Use of medicines potentially affecting blood glucose for more than 1 week cumulatively in the past 12 weeks, such as corticosteroids, growth hormone analogs, estrogen/progestogen, high-dose diuretics, antipsychotic drugs, etc.
- •Participation in another trial involving medicine therapy within the past 3 months.
- •Expected lifespan less than 2 years as per the investigator's clinical judgment, e.g., but not limited to malignancy.
- •Pregnant or lactating females, or females of childbearing potential who cannot or are unwilling to use adequate contraception.
- •Deemed unsuitable for participation in this clinical trial at the discretion of the investigator.
研究组 & 干预措施
Group A (triple combination therapy group)
semaglutide, empagliflozin, and pioglitazone treatment. 1) Initiate with Semaglutide 0.25 mg once weekly (qw) + Empagliflozin 10 mg once daily (qd) + Pioglitazone 15 mg once daily (qd); 2) After 1 month, if blood glucose is not controlled, adjust to Semaglutide 0.5 mg qw + Empagliflozin 20 mg qd + Pioglitazone 30 mg qd. If Semaglutide is well-tolerated, increase to 1 mg qw after 1 week; 3)If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.
干预措施: Group A (triple combination therapy group) (Drug)
Group B (standard therapy group)
metformin-based treatment is recommended when not contraindicated. 1).Initiate with Metformin monotherapy, titrate to the target dose of 1000 mg twice daily (bid) within 1 month or to the maximum tolerated dose (if Metformin is not tolerated, switch to Linagliptin 5 mg qd); 2) After 1 month, if blood glucose is not controlled, add a second antidiabetic drug, Empagliflozin 20 mg qd; 3) After another month, if blood glucose remains uncontrolled, add Semaglutide 0.25 mg qw, then increase to 0.5 mg qw after 1 month. If well-tolerated, increase to 1.0 mg qw after 1 week; 4) If blood glucose remains uncontrolled after 1 month, add basal insulin therapy.
干预措施: Group B (standard therapy group) (Drug)
结局指标
主要结局
Diabetic remission rate
时间窗: 6 months after discontinuation of medication
Diabetic remission rate at 6 months after discontinuation of medication (percentage of patients with HbA1c \<6.5% at 6 months after discontinuation of medication)
次要结局
- Time in range (TIR)(At baseline, at 6 months of medication treatment, and at 6 months after discontinuation of medication)
- Insulin resistance(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Diabetic remission rate(3 and 12 months after discontinuation of medication)
- Time required to achieve glycemic goal(6 months of medication)
- EQ-5D-5L questionnaires, quality of life(At baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication)
- Incremental cost per additional remission(6 months after discontinuation of medication)
- HbA1c(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Blood glucose level(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Blood insulin level(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Blood C-peptide level(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Pancreatic β-cell function(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Weight changes(baseline, at 6 months of medication, and at 3, 6, and 12 months after discontinuation of medication)
- Incremental cost per additional improvement in Time in Range (TIR)(6 months of medication treatment, and at 6 months after discontinuation of medication)
- Incremental cost per QALY gained(at baseline, at 6 months of medication treatment, and at 3, 6, and 12 months after discontinuation of medication)
研究者
Yanbing Li
Director of Endocrinology Department
Sun Yat-sen University