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?

Metformin versus placebo in patients with heart failure with preserved ejection fraction and obesity or insulin resistance (MET-HFpEF)

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

ISRCTN

Registry ID

ISRCTN74144960

Enrollment

Registered

2026-07-26

Start date

2026-08-01

Completion date

Unknown

Last updated

2026-08-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Heart failure with preserved ejection fraction (HFpEF), New York Heart Association (NYHA) Class II-III, insulin resistance, pre-diabetes, obesity Circulatory System

Interventions

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 SGLT

the comparator is a matching placebo (lactose).

Eligibility

Sex/Gender

All

Age

18 Years to 98 Years

Inclusion criteria

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

Exclusion criteria

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

Design outcomes

Primary

Measure	Time frame
Left ventricular mass index (normalised to height¹·7) measured using cardiac MRI at baseline and 12 months	—

Countries

Iraq

Contacts

Public ContactAram Mirza

arammerza@ymail.com+964 (0)7701570490

Outcome results

None listed

Source: ISRCTN (via WHO ICTRP) · Data processed: Aug 10, 2026