Heart Failure With Preserved Ejection FractionPhase 2/3NCT06080802
The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction
A Phase 2/3 study testing Metformin in people with Heart Failure With Preserved Ejection Fraction and Diabete Type 2, run by October University for Modern Sciences and Arts at 1 site in Egypt.
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 Read more about this study
- Who is it for?
- Ages 40 to 74 years
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction, Diabete Type 2
- What is being tested?
- Metformin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Nov 2023to 1 Dec 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Egypt1 site
clinical research uint- El-sheikh zayed specialized hospital SMC- Egyptian Ministry of health
Cairo
hassan abdellatif, 01092990402, hassangamal79@gmail.com
About this study
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
Read the 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
- Being tested
- Metformin
- Keywords
- metformin, SGLTi, HFpEF
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
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
| Study group | Role | What they receive |
|---|---|---|
| control(SGLT2i/ARBs/MRA/ +/- diuretics). | No intervention | Lifestyle counseling plus standard evidence-based therapy for HFpEF (SGLT2i/ARBs/MRA/ +/- diuretics). |
| intervention | Experimental | Lifestyle counseling plus standard evidence-based therapy for HFpEF (SGLT2i/ARBs/MRA/ +/- diuretics)+ metformin Receives: Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hospitalization rate
Hospitalization rate
Measured: baseline, 3 and 6 months
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)
Measured: baseline, 3 and 6 months
Secondary outcomes (6)
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
Measured: baseline, 3 and 6 months
adverse drug effects
adverse drugs effects
Measured: baseline, 3 and 6 months
Change in N-terminal pro-BNP (NT-proBNP)
Change in N-terminal pro-BNP (NT-proBNP)
Measured: baseline, 3 and 6 months
Neutrophil/lymphocyte ratio -AMPK pathway
Neutrophil/lymphocyte ratio
-AMPK pathway
Measured: baseline, 3 and 6 months
Inflammatory and oxidative stress
Inflammatory and oxidative stress
Measured: baseline, 3 and 6 months
Change in body weight
Change in body weight
Measured: baseline, 3 , 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2023
- Study start1 Nov 2023 (estimated)
- Primary completion1 Nov 2024 (estimated)
- Study completion1 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- October University for Modern Sciences and Arts
- Sponsor type
- University, hospital or other
- Collaborators
- clinical research unit, El-sheikh zayed specialized hospital - Egyptian Ministry of health
- Responsible party
- Sponsor
- Investigators
- sara M eladawy, Study director, MSA universityMai abdelhafez, PhD, Study chair, MSA university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06080802
- Sponsor's protocol ID
- C1/HEC1/2023PD
- Status last verified
- Oct 2023
- First submitted
- 8 Oct 2023
- Last updated
- 12 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36507650Kittleson 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.
PubMed 37137593
Study at a glance
From the registry record, last updated by the sponsor on 12 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Addition of Metformin to SGLT2 In Diabetic Patients With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT06080802
- Acronym / sponsor ID
- C1/HEC1/2023PD
- Keywords
- metformin, SGLTi, HFpEF
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- October University for Modern Sciences and ArtsUniversity, hospital or other
- Collaborators
- clinical research unit, El-sheikh zayed specialized hospital - Egyptian Ministry of health
- Study start
- 1 Nov 2023 (estimated)
- Primary completion
- 1 Nov 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 12 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| control(SGLT2i/ARBs/MRA/ +/- diuretics). | No intervention | –Lifestyle counseling plus standard evidence-based therapy for HFpEF (SGLT2i/ARBs/MRA/ +/- diuretics). |
| intervention | Experimental | Drug: MetforminLifestyle counseling plus standard evidence-based therapy for HFpEF (SGLT2i/ARBs/MRA/ +/- diuretics)+ metformin |
Who may qualify
- Ages
- 40 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminThe 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 | Drug | intervention |
Primary outcome
Hospitalization rate
Time frame: baseline, 3 and 6 months
Hospitalization rate
HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ)
Time frame: baseline, 3 and 6 months
HRQOL using Minnesota Living with Heart Failure Questionnaire for quality-of-life evaluation (MLFHQ)
6 secondary outcomes
The change in the mean early diastolic mitral annular velocity (mean e'), at 3 and 6 months
Time frame: baseline, 3 and 6 months
adverse drug effects
Time frame: baseline, 3 and 6 months
Change in N-terminal pro-BNP (NT-proBNP)
Time frame: baseline, 3 and 6 months
Neutrophil/lymphocyte ratio -AMPK pathway
Time frame: baseline, 3 and 6 months
Inflammatory and oxidative stress
Time frame: baseline, 3 and 6 months
Change in body weight
Time frame: baseline, 3 , 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Oct 2023.
- Background: PubMed 36507650ElSayed 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.
- Background: PubMed 37137593Kittleson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
sara M eladawy study director
MSA university
Mai abdelhafez, PhD study chair
MSA university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Metformin in people with Heart Failure With Preserved Ejection Fraction and Diabete Type 2, run by October University for Modern Sciences and Arts at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact sara M eladawy (01222124567, smeladway@msa.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hospitalization rate (time frame: baseline, 3 and 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06080802, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Oct 2023.