Heart Failure With Preserved Ejection FractionPhase 2Met-PEFNCT05093959
Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction
A Phase 2 study testing Metformin in people with Heart Failure With Preserved Ejection Fraction, run by Wake Forest University Health Sciences at 2 sites in United States.
Trial summary
Met-PEF will be a randomized, double-blind, placebo-controlled trial to examine the effects of 20 weeks of 1500 mg/day of metformin on physical function, quality of life (QOL), microbiome diversity, leaky gut, and systemic inflammation in patients with 86 older patients with heart failure with preserved ejection… Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Heart Failure With Preserved Ejection Fraction
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 86 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Jan 2022to 16 Apr 2026
- Phase
- Phase 2
- 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 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Heart failure with preserved ejection fraction (HFpEF) will be defined in accord with the American College of Cardiology/American Heart Association 2013 guidelines statement on Management of heart failure and as previously described. The 4 key inclusion criteria for HFpEF include: 1) clinical signs and symptoms as scored by National Health and Nutrition Examination Survey (NHANES)-HF Clinical Score ≥3 and the Rich Criteria; 2) a normal left ventricular (LV) ejection fraction (≥50%) by echocardiography; 3) LV diastolic dysfunction > grade 1 (American Society of Echocardiography Recommendations); 4) no evidence of significant ischemic, valvular, pulmonary or other medical disorder to account for their symptoms.
- Age ≥60
- Stable HF symptoms and medications for ≥3 weeks
- Final eligibility will be based upon all information available at the conclusion of the baseline visits tests, including review of hospital and outpatient records, history, physical examination, echocardiogram, and familiarization/screening exercise test by a board-certified investigator cardiologist who have extensive experience in heart failure investigations in older persons with HFpEF
Who cannot join
- History of treatment with metformin or other anti-diabetic drug intended to treat diabetes
- Body mass index (BMI) <25.0
- Uncontrolled dysrhythmia
- Uncontrolled hypertension (systolic blood pressure [SPB]>200 mmHg or diastolic blood pressure [DBP]>100 mmHg at rest)
- Significant anemia (<9.5 g hemoglobin [Hb]) (eligibility will be determined by complete blood count)
- Significant renal insufficiency (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2) (eligibility will be determined by comprehensive metabolic panel)
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- Acute or chronic metabolic acidosis
- Type 2 diabetes, or HbA1c>6.5
- Low vitamin B12 (<232 pg/mL)
- Known valvular heart disease, infiltrative cardiomyopathy, or hypertrophic obstructive cardiomyopathy with active obstruction as the primary etiology of HF
- Evidence of significant chronic obstructive pulmonary disease (COPD) defined as either: a. On continuous home oxygen therapy for COPD; b. Hospitalization for COPD in last 6 months
- Any condition that in the judgement of the investigator precludes participation in study or study procedures such as significant dementia, mobility impairment, uncontrolled psychiatric disease, etc.
- Alcohol abuse (>14 drinks/week)
- Current or recent cancer, or chemotherapy/radiation treatment
- Pregnancy-women of child-bearing potential are excluded from participation in this study.
- A treadmill exercise test revealing: a. Evidence of significant ischemia; b. Electrocardiogram: 1mm flat ST depression; c. Stopped exercising due to chest or leg claudication or any reason other than exhaustion/fatigue/dyspnea; d. Exercise SBP > 240 mmHg, DBP > 110 mmHg ; e. Unstable hemodynamics or rhythm; f. Unwilling or unable to complete adequate exercise test
- Exclusions for microbiome testing: a. Antibiotics use within last 30 days; b. Diarrhea and/or vomiting within last 30 days; c. Surgery related to gut in last 6 months; d. Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis), or irritable bowel syndrome
- Plans to leave area within 1 year
- Currently participating in other investigational study
- Refuses informed consent
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Atrium Health Sanger Heart and Vascular Clinic Institute
Charlotte, North Carolina, 28203
Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Met-PEF will be a randomized, double-blind, placebo-controlled trial to examine the effects of 20 weeks of 1500 mg/day of metformin on physical function, quality of life (QOL), microbiome diversity, leaky gut, and systemic inflammation in patients with 86 older patients with heart failure with preserved ejection fraction (HFpEF).
Read the detailed description
Enrollment of participants will be conducted at both Wake Forest and Atrium Health (approximately 43 participants at each site) following assessment of eligibility criteria and willingness to participate in the trial. Eligibility criteria are designed to target the population under study and exclude participants unable to safely take the study intervention or undergo study procedures. Informed consent will be obtained from qualified participants. Participants will complete baseline assessments before masked, random assignment to metformin or placebo. The assigned study medications will be dispensed by the research pharmacy. Participants will take assigned metformin or placebo for a treatment period of 20 weeks, starting at 500mg/day and escalating over the first 3 weeks to a target dose of 1500mg/day. Participants will be contacted every 2 weeks for assessment of adverse events, side effects, and adherence. At week 4, participants will be seen in clinic for safety laboratory assessments. At week 20, participants will complete follow-up assessments by an assessor blinded to treatment group.
- Being tested
- Metformin, Placebo
- Keywords
- heart failure, metformin, inflammation
- Medical subject headings
- Heart Failure, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called metformin XR
An extended release formulation will be used which improves compliance and reduces GI side effects.
PlaceboDrug
Placebo is a biologically inert substance placed in capsules to match appearance of active intervention
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | 20 weeks of metformin 1500 mg daily. Metformin is a widely used medication with an excellent safety profile. Dosing will be escalated during the first 3 weeks of treatment. Dosing will be initiated with 500 mg taken orally once daily in the evening for 1 week. After one week, the participant will be called to assess tolerance and will be asked to increase dose to two capsules per day for a total 1000 mg per day for one week. At the end of the second week, participants will be called again and if they tolerated the increased dose will be instructed to increase to three capsules (1500 mg/day) per day for the remainder of the 20 weeks. An extended release formulation will be used which improves compliance and reduces GI side effects. Receives: Drug: Metformin |
| Placebo | Placebo comparator | 20 weeks of placebo 1500 mg daily. Placebo is a biologically inert substance placed in capsules to match appearance of active intervention (metformin). Dosing will be escalated during the first 3 weeks of treatment. Dosing will be initiated with 500 mg taken orally once daily in the evening for 1 week. After one week, the participant will be called to assess tolerance and will be asked to increase dose to two capsules per day for a total 1000 mg per day for one week. At the end of the second week, participants will be called again and if they tolerated the increased dose will be instructed to increase to three capsules (1500 mg/day) per day for the remainder of the 20 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak VO2
Peak VO2 (ml of O2 relative to kg of body weight per minute [ml/kg/min]) is a measure of peak oxygen capacity during exercise, is a standardized, objective, reproducible and valid measure of exercise capacity.
Measured: Week 20
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start4 Jan 2022
- Primary completion18 Dec 2025
- Study completion16 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure With Preserved Ejection FractionStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 86 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- University of South Florida, National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Dalane W. Kitzman, MD, Principal investigator, Wake Forest University Health Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05093959
- Sponsor's protocol ID
- IRB00076663
- Other IDs
- U01AG076928
- Acronym
- Met-PEF
- Status last verified
- Aug 2025
- First submitted
- 22 Oct 2021
- Last updated
- 10 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No data are to be shared from this study.
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction
- ClinicalTrials.gov ID
- NCT05093959
- Acronym / sponsor ID
- Met-PEF / IRB00076663
- Keywords
- heart failure, metformin, inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 86 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Collaborators
- University of South Florida, National Institute on Aging (NIA)
- Study start
- 4 Jan 2022 (actual)
- Primary completion
- 18 Dec 2025 (actual)
- Study completion
- 16 Apr 2026 (actual)
- First posted
- 26 Oct 2021 (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.
Met-PEF will be a randomized, double-blind, placebo-controlled trial to examine the effects of 20 weeks of 1500 mg/day of metformin on physical function, quality of life (QOL), microbiome diversity, leaky gut, and systemic inflammation in patients with 86 older patients with heart failure with preserved ejection fraction (HFpEF).
Detailed description
Enrollment of participants will be conducted at both Wake Forest and Atrium Health (approximately 43 participants at each site) following assessment of eligibility criteria and willingness to participate in the trial. Eligibility criteria are designed to target the population under study and exclude participants unable to safely take the study intervention or undergo study procedures. Informed consent will be obtained from qualified participants. Participants will complete baseline assessments before masked, random assignment to metformin or placebo. The assigned study medications will be dispensed by the research pharmacy. Participants will take assigned metformin or placebo for a treatment period of 20 weeks, starting at 500mg/day and escalating over the first 3 weeks to a target dose of 1500mg/day. Participants will be contacted every 2 weeks for assessment of adverse events, side effects, and adherence. At week 4, participants will be seen in clinic for safety laboratory assessments. At week 20, participants will complete follow-up assessments by an assessor blinded to treatment group.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: Metformin20 weeks of metformin 1500 mg daily. Metformin is a widely used medication with an excellent safety profile. Dosing will be escalated during the first 3 weeks of treatment. Dosing will be initiated with 500 mg taken orally once daily in the evening for 1 week. After one week, the participant will be called to assess tolerance and will be asked to increase dose to two capsules per day for a total 1000 mg per day for one week. At the end of the second week, participants will be called again and if they tolerated the increased dose will be instructed to increase to three capsules (1500 mg/day) per day for the remainder of the 20 weeks. An extended release formulation will be used which improves compliance and reduces GI side effects. |
| Placebo | Placebo comparator | Drug: Placebo20 weeks of placebo 1500 mg daily. Placebo is a biologically inert substance placed in capsules to match appearance of active intervention (metformin). Dosing will be escalated during the first 3 weeks of treatment. Dosing will be initiated with 500 mg taken orally once daily in the evening for 1 week. After one week, the participant will be called to assess tolerance and will be asked to increase dose to two capsules per day for a total 1000 mg per day for one week. At the end of the second week, participants will be called again and if they tolerated the increased dose will be instructed to increase to three capsules (1500 mg/day) per day for the remainder of the 20 weeks. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Heart failure with preserved ejection fraction (HFpEF) will be defined in accord with the American College of Cardiology/American Heart Association 2013 guidelines statement on Management of heart failure and as previously described. The 4 key inclusion criteria for HFpEF include: 1) clinical signs and symptoms as scored by National Health and Nutrition Examination Survey (NHANES)-HF Clinical Score ≥3 and the Rich Criteria; 2) a normal left ventricular (LV) ejection fraction (≥50%) by echocardiography; 3) LV diastolic dysfunction > grade 1 (American Society of Echocardiography Recommendations); 4) no evidence of significant ischemic, valvular, pulmonary or other medical disorder to account for their symptoms.
- Age ≥60
- Stable HF symptoms and medications for ≥3 weeks
- Final eligibility will be based upon all information available at the conclusion of the baseline visits tests, including review of hospital and outpatient records, history, physical examination, echocardiogram, and familiarization/screening exercise test by a board-certified investigator cardiologist who have extensive experience in heart failure investigations in older persons with HFpEF
Key exclusion criteria (20 listed)
- History of treatment with metformin or other anti-diabetic drug intended to treat diabetes
- Body mass index (BMI) <25.0
- Uncontrolled dysrhythmia
- Uncontrolled hypertension (systolic blood pressure [SPB]>200 mmHg or diastolic blood pressure [DBP]>100 mmHg at rest)
- Significant anemia (<9.5 g hemoglobin [Hb]) (eligibility will be determined by complete blood count)
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 |
|---|---|---|
| MetforminAlso: metformin XRAn extended release formulation will be used which improves compliance and reduces GI side effects. | Drug | Metformin |
| PlaceboPlacebo is a biologically inert substance placed in capsules to match appearance of active intervention | Drug | Placebo |
Primary outcome
Peak VO2
Time frame: Week 20
Peak VO2 (ml of O2 relative to kg of body weight per minute [ml/kg/min]) is a measure of peak oxygen capacity during exercise, is a standardized, objective, reproducible and valid measure of exercise capacity.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2026.
- Individual participant dataSharing planned: No. No data are to be shared from this study.
Related trials for Heart Failure With Preserved Ejection Fraction
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The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
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Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
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Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
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ELEVATE-HFpEF Clinical Study
Heart Failure With Preserved Ejection Fraction (HFpEF)
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.
Dalane W. Kitzman, MD principal investigator
Wake Forest University Health Sciences
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Heart Failure With Preserved Ejection Fraction, run by Wake Forest University Health Sciences at 2 sites in United States.
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 4 inclusion and 20 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: finished, as of the sponsor's last update on 10 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Peak VO2 (time frame: Week 20). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 10 Jun 2026.