A Phase 2 interventional study of Metformin and Placebo in Heart Failure With Preserved Ejection Fraction, sponsored by Wake Forest University Health Sciences. Completed at 2 sites in United States. Open to participants aged 60 Years and older. Per ClinicalTrials.gov, last updated 2026-06-10.
Sponsored by Wake Forest University Health Sciences · Phase 2, Interventional, and Treatment
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).
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.
5,701 studies on the registry are indexed under Heart Failure; 1,220 are open to participants now.
This study's enrollment of 86 is above the median of 72 across 3,736 interventional studies indexed under Heart Failure.
Browse Heart Failure studies →Wake Forest University Health Sciences is the lead sponsor of 1,320 studies on the registry; 199 are open to participants now.
Of its 323 completed or terminated interventional studies of FDA-regulated products, 243 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
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.
Drug: Metformin
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.
Drug: Placebo
An extended release formulation will be used which improves compliance and reduces GI side effects.
Also known as: metformin XR
Placebo is a biologically inert substance placed in capsules to match appearance of active intervention
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.
Time frame: Week 20
C-reactive protein
Inflammatory marker in serum blood
Time frame: Week 20
Interleukin-6
Inflammatory marker in serum blood
Time frame: Week 20
Tumor necrosis factor-alpha
Inflammatory marker in serum blood
Time frame: Week 20
Kansas City Cardiomyopathy (KCCQ) Overall Score
The KCCQ overall score is the main summary score of the KCCQ containing physical, symptom, quality of life, and social subdomains. It is measured on a scale of 0-100 units with higher score indicating better HF-disease-specific quality of life.
Time frame: Week 20
Short Physical Performance Battery (SPPB)
The SPPB is a valid, clinically meaningful measure of physical function in older adults. The SPPB has 3 components: standing balance, 4-meter walk, and repeated chair rises, corresponding to balance, mobility, and functional strength. Each component is scored on a scale of 0-4 for a total score of 0-12 units with a higher score indicating better physical function.
Time frame: Week 20
6-minute walk distance (6MWD)
6MWD is the distance walked in 6 minutes, with higher distance indicating better function. The 6MWD test is a well-established outcome measure in heart failure. It is valid and reproducible in patients with a wide range of physical function, predicts clinical events, and responds to interventions.
Time frame: Week 20
Lipopolysaccharide binding protein (LBP)
LBP is a marker of microbial translocation, is increased in older persons and is related to their reduced physical function.
Time frame: Week 20
Fecal Mucin
Fecal mucin (mg/g) is a protein that indicates the mucus barrier functions and mucin production, measured by ELISA assays in feces. The higher the fecal mucin, better the mucus barriers are, or vice-versa.
Time frame: Week 20
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Plan to share: No — No data are to be shared from this study.
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Wake Forest University Health Sciences