The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

Official title:

The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06080802
• Other study ID #: C1/HEC1/2023PD
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• 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
• 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

Related Conditions & MeSH terms

• Diabete Type 2
• Diabetes Mellitus, Type 2
• Heart Failure
• Heart Failure With Preserved Ejection Fraction

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