Can metformin reduce heart muscle thickening and improve exercise capacity in people with heart failure with preserved ejection fraction who are overweight or have insulin resistance?
| ISRCTN | ISRCTN74144960 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN74144960 |
| Sponsor | University of Sulaimani |
| Funder | Investigator initiated and funded |
- Submission date
- 30/06/2026
- Registration date
- 26/07/2026
- Last edited
- 22/07/2026
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Circulatory System
Plain English summary of protocol
Background and study aims
Heart failure is a condition in which the heart cannot pump blood around the body efficiently. About half of people with heart failure have a type called heart failure with preserved ejection fraction (HFpEF), where the heart muscle still squeezes normally but is stiff and does not relax properly, causing breathlessness, tiredness and reduced ability to exercise. There are very few effective treatments. Many people with HFpEF are overweight or have insulin resistance (where the body cannot use insulin properly), which can thicken the heart muscle (left ventricular hypertrophy) and worsen symptoms. Metformin is a widely used, inexpensive diabetes medicine that can aid weight loss, reduce inflammation and improve insulin sensitivity; in earlier studies it reduced heart muscle thickness and improved exercise ability in heart failure. This study aims to find out whether metformin can reduce heart muscle thickness and improve exercise capacity in people with HFpEF who are overweight or have insulin resistance but do not have diabetes.
Who can participate?
Adults aged 18 years and over with symptomatic HFpEF (NYHA class II–III), evidence of a thickened heart muscle and preserved pumping function on an ultrasound scan, raised levels of a blood marker of heart strain (NT-proBNP) and either obesity or insulin resistance, who do not have diabetes and are taking a water tablet (loop diuretic).
What does the study involve?
Participants are randomly allocated to take either metformin (modified-release) or a matching dummy tablet (placebo) for 12 months; neither the participant nor the study team knows which they receive. The dose starts low and increases after two weeks if tolerated. Over 12 months participants attend visits (with some telephone check-ins) for safety blood tests, an exercise test, heart MRI and ultrasound scans, and a quality-of-life questionnaire. Heart muscle thickness (by MRI) and exercise capacity are compared between the start and end of the study.
What are the possible benefits and risks of participating?
Participants may not benefit directly, but the study may show whether metformin helps people with HFpEF and could lead to a larger trial. Metformin's most common side effects are stomach-related (loss of appetite, nausea, vomiting, diarrhoea, abdominal discomfort, and a metallic taste), usually mild and self-limiting; a very rare side effect is a build-up of acid in the blood (lactic acidosis). People at higher risk are excluded, and participants are monitored with regular blood tests. The heart MRI involves a contrast dye injection and is not suitable for everyone (e.g., certain implants or claustrophobia).
Where is the study run from?
University of Sulaimani (Iraq)
When is the study starting and how long is it expected to run for?
August 2026 to
Who is funding the study?
Who is the main contact?
Contact information
Public, Scientific, Principal investigator
German Village 82
Sulaymaniah
46001
Iraq
| Phone | +964 (0)7701570490 |
|---|---|
| arammerza@ymail.com |
Study information
| Primary study design | Interventional |
|---|---|
| Allocation | Randomized controlled trial |
| Masking | Blinded (masking used) |
| Control | Placebo |
| Assignment | Parallel |
| Purpose | Treatment |
| Scientific title | Metformin versus placebo in patients with heart failure with preserved ejection fraction and obesity or insulin resistance (MET-HFpEF) |
| Study acronym | MET-HFpEF |
| Study objectives | |
| Ethics approval(s) |
Approved 13/05/2026, The Ethics Committee of the College of Medicine (University of Sulaimani, Sulaimani, 46001, Iraq; +964 (0)533270924; med.ethics@univsul.edu.iq), ref: 153 (Ethics Committee Meeting No. 17) |
| Health condition(s) or problem(s) studied | Heart failure with preserved ejection fraction (HFpEF), New York Heart Association (NYHA) Class II-III, insulin resistance, pre-diabetes, obesity |
| Intervention | Eligible participants will be randomised in a 1:1 ratio to either metformin modified-release or matched placebo. Randomisation will be stratified by the presence of atrial fibrillation and use of SGLT2 inhibitors, and the proportion of participants in atrial fibrillation will be limited to 40% of the total cohort. The randomisation sequence will be generated by an independent statistician using a validated computer-based randomisation system. Metformin (modified-release) is titrated from 500 mg twice daily to 1000 mg twice daily (2000 mg/day) for 12 months; the comparator is a matching placebo (lactose). |
| Intervention type | Drug |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Metformin |
| Primary outcome measure(s) |
|
| Key secondary outcome measure(s) | |
| Completion date | 01/08/2027 |
Eligibility
| Participant type(s) | |
|---|---|
| Age group | Mixed |
| Lower age limit | 18 Years |
| Upper age limit | 98 Years |
| Sex | All |
| Target sample size at registration | 66 |
| Key inclusion criteria | 1. Willing/able to consent 2. Aged ≥18 years 3. Symptomatic HFpEF (NYHA II–III) 4. Elevated indexed left ventricular (LV) mass on screening echo (males >81 g/h¹·⁷, females >60 g/h¹·⁷) 5. Insulin resistance (Fasting Insulin Resistance Index [FIRI] ≥2.7) or pre-diabetes (HbA1c 39–47 mmol/mol) or body mass index (BMI) ≥30 kg/m² 6. NT-proBNP >300 pg/mL (sinus rhythm) or >600 pg/mL (AF) 7. Left ventricular ejection fraction (LVEF) ≥45% 8. On loop diuretics 9. Able/willing to comply |
| Key exclusion criteria | 1. Type 1 or 2 diabetes 2. HbA1c >47 mmol/mol 3. SBP >180 mmHg 4. eGFR <30 ml/min/1.73 m² 5. Contraindications to CMR 6. Previous LVEF <40% 7. Metformin hypersensitivity 8. Severe cognitive impairment 9. Active malignancy or other life-threatening disease 10. Hepatic insufficiency or history of alcoholism 11. Acute conditions affecting renal function 12. Pregnancy/lactation 13. Participation in another trial within 30 days 14. Investigator discretion |
| Date of first enrolment | 01/08/2026 |
| Date of final enrolment | 31/08/2026 |
Locations
Countries of recruitment
- Iraq
Study participating centres
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|
Editorial Notes
22/07/2026: Study's existence confirmed by the Ethics Committee of the College of Medicine of the University of Sulaimani.
