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Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06080802
Other study ID # C1/HEC1/2023PD
Secondary ID
Status Not yet recruiting
Phase Phase 2/Phase 3
First received
Last updated
Start date November 1, 2023
Est. completion date December 1, 2024

Study information

Verified date October 2023
Source October University for Modern Sciences and Arts
Contact sara M eladawy
Phone 01222124567
Email smeladway@msa.edu.eg
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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


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


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 80
Est. completion date December 1, 2024
Est. primary completion date November 1, 2024
Accepts healthy volunteers No
Gender All
Age group 40 Years to 74 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Metformin
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

Locations

Country Name City State
Egypt clinical research uint- El-sheikh zayed specialized hospital SMC- Egyptian Ministry of health Cairo

Sponsors (2)

Lead Sponsor Collaborator
October University for Modern Sciences and Arts clinical research unit, El-sheikh zayed specialized hospital - Egyptian Ministry of health

Country where clinical trial is conducted

Egypt, 

References & Publications (2)

ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, on behalf of the American Diabetes Association. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care. 2023 Jan 1;46(Suppl 1):S140-S157. doi: 10.2337/dc23-S009. — View Citation

Kittleson MM, Panjrath GS, Amancherla K, Davis LL, Deswal A, Dixon DL, Januzzi JL Jr, Yancy CW. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2023 May 9;81(18):1835-1878. doi: 10.1016/j.jacc.2023.03.393. Epub 2023 Apr 19. No abstract available. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Hospitalization rate Hospitalization rate baseline, 3 and 6 months
Primary HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ) HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ) baseline, 3 and 6 months
Secondary The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months baseline, 3 and 6 months
Secondary adverse drug effects adverse drugs effects baseline, 3 and 6 months
Secondary Change in N-terminal pro-BNP (NT-proBNP) Change in N-terminal pro-BNP (NT-proBNP) baseline, 3 and 6 months
Secondary Neutrophil/lymphocyte ratio -AMPK pathway Neutrophil/lymphocyte ratio
-AMPK pathway
baseline, 3 and 6 months
Secondary Inflammatory and oxidative stress Inflammatory and oxidative stress baseline, 3 and 6 months
Secondary Change in body weight Change in body weight baseline, 3 , 6 months
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