Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction

NCT05093959 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: IRB00076663U01AG076928
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 2

Brief 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 fraction (HFpEF).

Conditions

Heart Failure With Preserved Ejection Fraction

Keywords

heart failure, metformin, inflammation

Outcome Measures

Primary Outcomes (1)

• 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.

  Week 20

Other Outcomes (8)

• C-reactive protein

  Week 20

• Interleukin-6

  Week 20

• Tumor necrosis factor-alpha

  Week 20

Study Arms (2)

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.

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.

Drug: Placebo

Interventions

Metformin DRUG

An extended release formulation will be used which improves compliance and reduces GI side effects.

Also known as: metformin XR

Metformin

Placebo DRUG

Placebo is a biologically inert substance placed in capsules to match appearance of active intervention

Placebo

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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.

Sponsors & Collaborators

• Wake Forest University Health Sciences: lead
• University of South Florida: collaborator
• National Institute on Aging (NIA): collaborator

Study Sites (2)

Atrium Health Sanger Heart and Vascular Clinic Institute

Charlotte, North Carolina, 28203, United States

Location

Wake Forest School of Medicine

Winston-Salem, North Carolina, 27157, United States

Location

MeSH Terms

Conditions

Heart Failure; Inflammation

Interventions

Metformin

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Dalane W. Kitzman, MD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants, care providers, investigators, and outcomes assessors will be unmasked at the end of data collection of all participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2021
• First Posted: October 26, 2021
• Study Start: January 4, 2022
• Primary Completion: December 18, 2025
• Study Completion: April 16, 2026
• Last Updated: May 5, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)