What diabetes medications should be avoided in patients with Heart Failure (HF)?

Thiazolidinediones (TZDs) Must Be Avoided in Heart Failure Patients

Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with established heart failure and should not be used in patients at risk of developing heart failure. 1

Primary Medications to Avoid

Thiazolidinediones (TZDs) - Absolute Contraindication

• TZDs are contraindicated in all patients with established HF (both HFrEF and HFpEF), regardless of functional class 1
• Both rosiglitazone and pioglitazone cause fluid retention through increased renal sodium reabsorption, leading to volume expansion and HF events 1
• The risk of HF hospitalization or death approximately doubles with TZD use (OR 2.10 for rosiglitazone) 2
• Rosiglitazone carries higher HF risk than pioglitazone (OR 2.73 vs 1.51), though both are contraindicated 3
• TZDs increase HF risk even in patients without baseline HF, making them inappropriate for diabetic patients at high risk for developing HF 1

DPP-4 Inhibitors - Specific Agent to Avoid

• Saxagliptin is not recommended in patients with HF or at high risk of HF due to increased HF hospitalization risk 1
• Sitagliptin and linagliptin show no increased HF signal and may be considered if needed 1

Medications to Use with Caution

GLP-1 Receptor Agonists

• Avoid in patients with recent HF decompensation 1
• May be used in stable HF patients, as they show neutral effects on HF hospitalization in cardiovascular outcomes trials 1

Insulin

• Use with caution due to associations with weight gain, hypoglycemia risk, and observational data suggesting increased mortality in HF patients 1
• However, insulin is sometimes necessary for adequate glycemic control and is the preferred agent when eGFR <30 mL/min/1.73 m² 1

Preferred Medications in HF Patients

First-Line Agents

• SGLT-2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) are recommended to decrease HF hospitalization risk 1
• Metformin is preferred if eGFR >30 mL/min/1.73 m² 1

Clinical Decision Algorithm

For patients with established HF:

1. Immediately discontinue TZDs if currently prescribed 1
2. Initiate or continue SGLT-2 inhibitors as first-line diabetes therapy 1
3. Add metformin if eGFR >30 mL/min/1.73 m² 1
4. Avoid saxagliptin; consider sitagliptin or linagliptin if DPP-4 inhibitor needed 1
5. Reserve insulin for patients unable to achieve glycemic control with preferred agents 1

For patients at high risk of HF (without established HF):

1. Do not initiate TZDs 1
2. Prefer SGLT-2 inhibitors and metformin 1
3. Avoid saxagliptin 1

Critical Pitfalls to Avoid

• Do not continue TZDs in patients who develop symptomatic HF while on therapy - this is an absolute indication for discontinuation 2
• Do not assume pioglitazone is safe because it has cardiovascular benefits - both TZDs are contraindicated in HF despite pioglitazone's potential macrovascular benefits 4
• Do not use TZDs in elderly patients, those with elevated BMI, microalbuminuria, or elevated systolic blood pressure - these are independent predictors of TZD-associated HF events 2
• The mechanism is volume expansion, not reduced ejection fraction, so normal echocardiography does not exclude risk 1