Metformin to improve heart function after LVAD placement

Inclusion Criteria:

* Age 18-75 years
* Receiving continuous-flow LVADs, such as HeartMate 3, HVAD, Core-Heart 6, Brio-Heart
* Presence of insulin resistance
* HbA1c ≤ 6.5%

Exclusion Criteria:

* Diagnosed type 1 diabetes mellitus, or type 2 diabetes mellitus with HbA1c \> 6.5% (patients with prior type 2 diabetes who are currently off therapy and have HbA1c ≤ 6.5% may be enrolled; such patients may still have insulin resistance but have achieved glycemic control)
* History of diagnosed diabetic ketoacidosis or hyperosmolar hyperglycemic state
* Currently using any glucose-lowering medications (including insulin, oral hypoglycemic agents, GLP-1 receptor agonists, SGLT2 inhibitors, etc.)
* History of diagnosed polycystic ovary syndrome (PCOS) and currently undergoing treatment
* Estimated glomerular filtration rate (eGFR) \< 45 mL/min/1.73 m² (CKD-EPI equation)
* History of acute kidney injury (KDIGO criteria) with incomplete renal recovery
* Receiving any form of renal replacement therapy (hemodialysis, peritoneal dialysis)
* Post-kidney transplantation or awaiting kidney transplantation
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3× the upper limit of normal, total bilirubin \> 2× upper limit of normal, or Child-Pugh class B or C cirrhosis
* Active viral hepatitis
* History of alcoholic liver disease or drug-induced liver injury currently in the active phase
* Concurrent right ventricular assist device (RVAD) or total artificial heart implantation
* LVAD-related complications requiring surgical intervention within 30 days postoperatively, including but not limited to: pump thrombosis requiring LVAD exchange or thrombolysis, driveline infection requiring debridement or replacement, hemorrhagic complications requiring re-sternotomy, device malfunction requiring urgent intervention
* Acute kidney injury requiring ongoing renal replacement therapy (CRRT) within 30 days postoperatively
* Preoperative severe right heart failure (on echocardiography: right ventricular fractional area change \< 35%, or tricuspid annular plane systolic excursion \< 14 mm; or right heart catheterization showing central venous pressure \> 15 mmHg and cardiac index \< 2.0 L/min/m²)
* Preoperative severe pulmonary arterial hypertension (mean pulmonary arterial pressure ≥ 40 mmHg and pulmonary vascular resistance ≥ 4 Wood units)
* Within 30 days postoperatively, occurrence of severe low cardiac output syndrome requiring extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pump (IABP) support
* Significant prosthetic valve dysfunction or severe prosthetic valve infectious endocarditis
* Severe unrepaired valvular disease
* Active systemic infection or sepsis requiring ongoing intravenous antibiotics or antifungal therapy
* Active infectious endocarditis (modified Duke criteria) or high clinical suspicion
* Human immunodeficiency virus (HIV) infection with CD4 count \< 200/μL or not on regular antiretroviral therapy
* Active tuberculosis or non-tuberculous mycobacterial infection
* Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection
* Known active inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease) currently requiring immunosuppressive therapy
* Platelet count \< 50 × 10⁹/L, hemoglobin \< 80 g/L, international normalized ratio (INR) \> 3.0 and not reversible (unless on warfarin with INR within the target range)
* Known bleeding disorders (e.g., hemophilia, von Willebrand disease, acquired von Willebrand syndrome)
* Malignancy diagnosed within the past 5 years (except for cured thyroid cancer, breast cancer, lung cancer, cervical cancer, etc.) and currently receiving chemotherapy, radiotherapy, or targeted therapy
* Prior recipients of heart transplantation or other organ transplants
* Patients awaiting heart transplantation with an anticipated waiting time of less than 3 months
* Pregnant or lactating women
* Reproductive-age women who are capable of conceiving but refuse to use effective contraception during the study period (including surgical sterilization, intrauterine device, oral contraceptives, condoms, etc.)
* Women planning pregnancy during the study
* Known allergy to metformin or any drug excipient
* Known history of lactic acidosis
* Currently using medications that may significantly increase the risk of lactic acidosis, including but not limited to: carbonic anhydrase inhibitors (topiramate, acetazolamide), antiretroviral drugs (especially nucleoside reverse transcriptase inhibitors), certain chemotherapeutic agents (cisplatin)
* Currently using medications that may affect glycemic control or insulin sensitivity and that cannot be stopped or substituted during the study, including but not limited to: systemic glucocorticoids (prednisone-equivalent dose \> 10 mg/day for \> 2 weeks), high-dose thiazide diuretics (hydrochlorothiazide \> 50 mg/day), atypical antipsychotics (olanzapine, clozapine, etc.), immunosuppressants (tacrolimus, cyclosporine, etc.)
* Unable to complete 12-month follow-up
* Known psychiatric disorders or cognitive impairment that may affect informed consent validity or study compliance
* History of drug or alcohol abuse (within the past year)
* Concurrent participation in another clinical trial
* Any other circumstance, as determined by the investigator, that would render the subject unsuitable for enrollment (including but not limited to social, psychological, or geographic factors)