Efficacy and safety of Fixed dose combinations of newer SGLT2 and DPP-IV inhibitors versus therapy with each mono-component, in poorly controlled type 2 diabetes on Metformin: A Randomized open-label trial
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Mean change in HbA1c from baseline
研究概览
简要总结
Diabetes mellitus refers to a group of metabolic disorders that share the phenotype of hyperglycemia. Several distinct types of diabetes are caused by a complex interaction of genetics and environmental factors. Depending on the etiology of diabetes, factors contributing to hypergycemia comprise reduced insulin secretion, decreased glucose utilization, and increased glucose production.
Although achievement of optimal glycaemic control is an important aim of type 2 diabetes treatment, available data indicate poor attainment of glycaemic targets in clinical practice.Clinical inertia, defined as failure to intensify antiâ€hyperglycaemic therapy in a timely manner, has been proposed as one explanation for these findings when sequential therapy is used. Although many factors contribute to clinical inertia, this traditional sequential treatment paradigm for type 2 diabetes, comprising stepwise addition of antiâ€hyperglycaemic agents to initial metformin monotherapy in response to increased glycated haemoglobin (HbA1c) levels, may be a major reason why some patients experience delays in reaching their glycaemic goals.
An alternative approach to type 2 diabetes treatment is simultaneous combination therapy with antiâ€hyperglycaemic agents that have complementary mechanisms of action, and therefore target multiple physiological defects. Several studies have shown that firstâ€line dual therapy, combining antiâ€hyperglycaemic agents, had greater efficacy than the components as monotherapies without increasing the risk of hypoglycaemia
In a 24â€week study in patients with baseline HbA1c 8.0% to 12.0% and in whom metformin failed, triple therapy achieved by concomitant dual addition of the sodiumâ€glucose coâ€transporterâ€2 (SGLT2) inhibitor dapagliflozin (highest dose of 10 mg/d) and the dipeptidyl peptidaseâ€4 (DPPâ€4) inhibitor saxagliptin (5 mg/d) led to greater HbA1c reductions than the addition of either agent alone to metformin. In addition, a recent 24â€week trial demonstrated that the same triple therapy combination had greater glucoseâ€lowering efficacy, and was associated with substantially lower incidence of hypoglycemia , than glimepiride, a sulphonylurea, added on to metformin. Another study on Combination of Empagliflozin and Linagliptin as Second-Line Therapy in Subjects With Type 2 Diabetes Inadequately controlled on metformin showed significant reduction in HbA1c compared with the individual components and were well tolerated.
Initiating simultaneous combination therapy at early stages of the disease, rather than by the sequential stepwise approach, may permit earlier achievement of glycaemic goals, more durable efficacy, and better preservation of βâ€cell function than gradual treatment intensification. A recent Consensus recommends the use of combination therapy in patients who present with an HbA1c level that is >1.5-2.0% above an individualized HbA1c target, based on the knowledge that most oral glucoseâ€lowering therapies do not result in HbA1c reductions of >1.0% when given as monotherapies. By contrast, guidelines from the American Association of Clinical Endocrinologists (AACE) recommend the use of initial combination therapy in patients with an HbA1c level ≥ 7.5%.
The study has been chosen keeping the primary Aim:
ü To evaluate the efficacy and safety of a combination therapy comprising a sodium-glucose cotransporter type 2 inhibitor (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP4i) in uncontrolled type 2 diabetes mellitus on Metformin
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Open Label
入排标准
- 年龄范围
- 18.00 Year(s) 至 99.00 Year(s)（—）
- 性别
- All
入选标准
- •Age ≥ 18 years Diagnosis of type 2 diabetes On metformin dose (≥1000 mg/d) HbA1c ≥8 to 10.0% Fasting plasma glucose (FPG) ≤15 mmol/L (≤270 mg/dl) Exclusion criteria.
排除标准
- •Type 1 diabetic patient and patient on Insulin Pregnancy, diabetic ketoacidosis A cardiovascular event in the 3 months before enrolment.
- •Moderate or severe impairment of renal function (estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2).
结局指标
主要结局
Mean change in HbA1c from baseline
时间窗: Mean change in HbA1c from baseline, 12 weeks and 24 weeks
次要结局
- The proportion of participants achieving a therapeutic glycemic response HbA1cless than 7.0%(at 24 weeks)
- fasting plasma glucose (FPG)(From baseline to week 12 and 24)
- postprandial blood sugar(PPBS)(from baseline to week 12 and 24)
- Total body weight(from baseline to week 12 and 24)
- mean change in systolic and diastolic BP(from baseline to week 12 and 24)