Diabete Type 2, Heart Failure With Preserved Ejection Fraction
Conditions
Keywords
metformin, SGLTi, HFpEF
Brief summary
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
Detailed description
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
Interventions
DRUGMetformin
The intervention will consist in giving metformin starting with 500 mg once daily 1 gm daily (at breakfast) during the first week; if well tolerated, the dose was progressively increased to 500 mg twice daily (at breakfast and dinner) during week 2, to 1000 mg at breakfast and 500 mg at dinner during week 3, in order to reach the target dose of 1000 mg twice daily (at breakfast and dinner) during the rest of the follow-up. Patients will be followed up by telephone call 2 weeks intervals during the study period 5 SGL-2 will be prescribed to group 1 after diagnosis with HFpEF while group 2 will have SGL-2 and Metformin
Sponsors
clinical research unit, El-sheikh zayed specialized hospital - Egyptian Ministry of health
October University for Modern Sciences and Arts
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 74 Years
Healthy volunteers
No
Inclusion criteria
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
Exclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hospitalization rate | baseline, 3 and 6 months | Hospitalization rate |
| HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ) | baseline, 3 and 6 months | HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in N-terminal pro-BNP (NT-proBNP) | baseline, 3 and 6 months | Change in N-terminal pro-BNP (NT-proBNP) |
| Neutrophil/lymphocyte ratio -AMPK pathway | baseline, 3 and 6 months | Neutrophil/lymphocyte ratio -AMPK pathway |
| The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months | baseline, 3 and 6 months | The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months |
| Change in body weight | baseline, 3 , 6 months | Change in body weight |
| Inflammatory and oxidative stress | baseline, 3 and 6 months | Inflammatory and oxidative stress |
| adverse drug effects | baseline, 3 and 6 months | adverse drugs effects |
Countries
Egypt
Contacts
Primary Contactsara M eladawy
Backup Contacthassan abdellatif
Outcome results
None listed