Clinical trial NCT06080802: The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction
Official title: The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Heart Failure With Preserved Ejection Fraction
Diabete Type 2
Keywords: metformin
SGLTi
HFpEF
Lead sponsor: October University for Modern Sciences and Arts
Sponsor class: OTHER
Collaborators: name: clinical research unit, El-sheikh zayed specialized hospital - Egyptian Ministry of health
First posted: 2023-10-12
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Maximum age (years): 74
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Hospitalization rate
timeFrame: baseline, 3 and 6 months
measure: HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ)
timeFrame: baseline, 3 and 6 months
Secondary outcomes:
measure: The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months
timeFrame: baseline, 3 and 6 months
measure: adverse drug effects
timeFrame: baseline, 3 and 6 months
measure: Change in N-terminal pro-BNP (NT-proBNP)
timeFrame: baseline, 3 and 6 months
measure: Neutrophil/lymphocyte ratio -AMPK pathway
timeFrame: baseline, 3 and 6 months
measure: Inflammatory and oxidative stress
timeFrame: baseline, 3 and 6 months
measure: Change in body weight
timeFrame: baseline, 3 , 6 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: clinical research uint- El-sheikh zayed specialized hospital SMC- Egyptian Ministry of health
Study officials:
affiliation: MSA university
name: sara M eladawy
role: STUDY_DIRECTOR
affiliation: MSA university
name: Mai abdelhafez, PhD
role: STUDY_CHAIR
References:
citation: 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.
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.