What are the recommended oral hypoglycemic agents (OHAs) for managing diabetes in patients with heart failure?

Oral Hypoglycemic Agents in Heart Failure

SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) are the recommended first-line oral hypoglycemic agents for patients with type 2 diabetes and heart failure, as they reduce both HF hospitalizations and cardiovascular mortality. 1

Primary Recommendations

SGLT2 Inhibitors (First-Line)

• Empagliflozin, canagliflozin, or dapagliflozin are Class I recommendations to lower the risk of heart failure hospitalization in patients with diabetes and established HF or those at high cardiovascular risk 1
• Empagliflozin specifically reduces the risk of death in patients with type 2 diabetes and cardiovascular disease 1
• These agents benefit patients irrespective of diabetes status, as they reduce HF hospitalizations and cardiovascular mortality even in non-diabetic HF patients 1

Metformin (Second-Line)

• Metformin should be considered in patients with diabetes and HF if eGFR >30 mL/min/1.73 m² 1
• Can be used safely in patients with stable heart failure and normal renal function 1
• Must be avoided in unstable or hospitalized HF patients and those with significant renal dysfunction (eGFR <30 mL/min) due to lactic acidosis risk 1

Agents That May Be Considered

GLP-1 Receptor Agonists

• Liraglutide, semaglutide, or dulaglutide are recommended to reduce cardiovascular events in patients with type 2 diabetes and CVD 1
• Liraglutide specifically reduces the risk of death 1
• GLP-1 RAs have a neutral effect on HF risk and may be considered 1

DPP-4 Inhibitors (Select Agents Only)

• Sitagliptin and linagliptin have a neutral effect on HF risk and may be considered 1
• These are acceptable alternatives when SGLT2 inhibitors or metformin cannot be used 1

Insulin

• Insulin treatment in HF may be considered when oral agents fail to achieve glycemic targets 1
• Should be initiated early if glucose targets cannot be achieved with safer oral agents 1

Agents to AVOID

Contraindicated or Not Recommended

Thiazolidinediones (Pioglitazone and Rosiglitazone)

• Absolutely contraindicated in patients with NYHA Class III-IV heart failure 1
• Cause fluid retention and exacerbate heart failure 1, 2
• May be considered with extreme caution only in NYHA Class I-II with careful monitoring for fluid retention, but this is generally not recommended given safer alternatives 1
• FDA labeling specifically warns that pioglitazone can cause or exacerbate heart failure and should be discontinued if HF develops 2

Saxagliptin (DPP-4 Inhibitor)

• Not recommended in patients with type 2 diabetes and high risk of HF 1
• Associated with increased risk of hospitalization for heart failure 1

Clinical Algorithm for Selection

Step 1: Start with SGLT2 inhibitor (empagliflozin, canagliflozin, or dapagliflozin) as first-line therapy 1

Step 2: If additional glycemic control needed and eGFR >30 mL/min, add metformin 1

Step 3: If further control needed, consider:

• GLP-1 receptor agonist (liraglutide, semaglutide, or dulaglutide) for additional cardiovascular benefit 1
• Sitagliptin or linagliptin (neutral HF effect) 1

Step 4: Add insulin if oral agents insufficient 1

Critical Caveats

• Never use thiazolidinediones in any patient with symptomatic HF (NYHA Class III-IV) 1, 2
• Avoid saxagliptin entirely in HF patients 1
• Monitor renal function closely when using metformin; stop if eGFR falls below 30 mL/min 1
• Avoid aggressive glycemic control that increases hypoglycemia risk, as hypoglycemia can trigger arrhythmias in HF patients 1
• The 2019 ESC guidelines represent the most current evidence and supersede older 2008 recommendations that lacked data on SGLT2 inhibitors 1