The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Hospitalization rate
研究概览
简要总结
a prospective open-label, randomized controlled study to evaluate the efficacy of the addition of metformin to SGLT2 in diabetic patient with preserved ejection fraction
详细描述
Regardless of the benefits noted with SGLT2is, metformin is recommended as first-line therapy for glycemic control in individuals with T2DM and HF, including HFpEF, with estimated glomerular filtration rates (eGFRs) ≥30 mL/min/1.73 m2. This is based on the demonstrated experience with long-term use; its safety, low cost, and low side effect profile; as well as observational (not clinical trial) data suggesting a 20% relative risk reduction in mortality in individuals with HF, including HFpEF.
Nevertheless, it is worth mentioning that Metformin is a common anti-diabetic drug with both systemic and cardioprotective benefits in addition to its hypoglycaemic effect. At the cellular level metformin activates adenosine monophosphate-activated protein kinase (AMPK) an important regulator of several metabolic pathways resulting in enhanced glucose utilisation, reduction of protein synthesis and improvement of mitochondrial function. Furthermore, metformin has been shown to reduce collagen accumulation and potentially reduce LV hypertrophy and improve diastolic function in the diabetic myocardium. The cardio protection afforded by metformin treatment seems to result from interference with TGF-beta signaling pathway and activation of the AMP-kinase signaling cascade. A recent systematic review and meta regression analysis have shown that metformin treatment was associated with a reduction in mortality in patients with HFpEF. In addition, treatment with metformin of non-diabetic metabolic syndrome patients with diastolic dysfunction, on top of lifestyle counseling, was associated with improved diastolic function.
Nevertheless, a recent met analysis showed that initial SGLT2 inhibitor/metformin combination therapy has glycaemic and weight benefits compared with either agent alone and appears relatively safe. High dose SGLT2 inhibitor/metformin combination therapy appears to have modest weight, but no glycaemic benefits compared with the low dose combination therapy.
based on that we our aim is to evaluate the efficacy of the addition of metformin to SGLT2 in diabetic patient with preserved ejection fraction
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
- 40 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age of 40 years to 74 years. HFpEF (≥ 50%) Written informed consent of the subject to participate in the study. New York Heart Association functional class I-IV. Diabetic patients SGL-2 naive. Newly diagnosed heart failure of preserved ejection fraction
排除标准
- •Patients with heart failure with reduced ejection fraction (< 40%) Age less than 40 and more than 74 GFR < 30 mL/min A1c > 9 Known allergy to metformin End- stage liver disease Cancer Pregnancy or lactation
研究组 & 干预措施
intervention
Lifestyle counseling plus standard evidence-based therapy for HFpEF (SGLT2i/ARBs/MRA/ +/- diuretics)+ metformin
干预措施: Metformin (Drug)
结局指标
主要结局
Hospitalization rate
时间窗: baseline, 3 and 6 months
Hospitalization rate
HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ)
时间窗: baseline, 3 and 6 months
HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ)
次要结局
- The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months(baseline, 3 and 6 months)
- adverse drug effects(baseline, 3 and 6 months)
- Neutrophil/lymphocyte ratio -AMPK pathway(baseline, 3 and 6 months)
- Change in N-terminal pro-BNP (NT-proBNP)(baseline, 3 and 6 months)
- Change in body weight(baseline, 3 , 6 months)
- Inflammatory and oxidative stress(baseline, 3 and 6 months)