In a patient with type 2 diabetes mellitus and heart failure who is taking metformin 500 mg twice daily, which glucose‑lowering medication should be avoided?

Avoid Thiazolidinediones in Patients with Type 2 Diabetes and Heart Failure

You should avoid thiazolidinediones (pioglitazone, rosiglitazone) in this patient with type 2 diabetes and heart failure, as these medications have a strong and consistent relationship with increased risk of heart failure. 1

Why Thiazolidinediones Are Contraindicated

• Thiazolidinediones should be avoided in people with symptomatic heart failure due to robust evidence demonstrating they increase heart failure risk across multiple studies. 1

• The data on glucose-lowering agents and heart failure outcomes consistently show that thiazolidinediones have the strongest association with worsening heart failure among all diabetes medications. 1

• This contraindication applies specifically to patients with symptomatic heart failure, which your patient has. 1

What You Should Consider Instead

SGLT2 Inhibitors (Preferred Choice)

• SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) are the preferred add-on therapy in patients with diabetes and heart failure, as they reduce heart failure hospitalization by 27-35% compared to placebo. 1

• These agents improve heart failure-related outcomes including hospitalization and symptoms in patients with both preserved and reduced ejection fraction. 1

GLP-1 Receptor Agonists (Safe Alternative)

• GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide) have shown no increased risk of heart failure hospitalization in cardiovascular outcomes trials and may reduce cardiovascular events. 1

Metformin (Continue Current Therapy)

• Continue the patient's current metformin therapy, as it is safe in stable heart failure when kidney function remains within the recommended range (eGFR >30 mL/min/1.73 m²). 1, 2

• Observational studies suggest metformin users with type 2 diabetes and heart failure have better outcomes than patients on other antihyperglycemic agents. 1, 2

Important Caveats About DPP-4 Inhibitors

• Exercise caution with saxagliptin specifically, as the SAVOR-TIMI 53 trial showed increased heart failure hospitalization (3.5% vs. 2.8% with placebo). 1

• Other DPP-4 inhibitors (alogliptin, sitagliptin, linagliptin) did not show increased heart failure risk in their respective cardiovascular outcomes trials, though they lack the heart failure benefits seen with SGLT2 inhibitors. 1

• While not absolutely contraindicated like thiazolidinediones, avoid sitagliptin, sulfonylureas, and thiazolidinediones in patients with heart failure according to European cardiovascular guidelines. 1

Clinical Algorithm for This Patient

1. Discontinue any thiazolidinedione immediately if the patient were taking one. 1

2. Add an SGLT2 inhibitor as the next glucose-lowering medication to both improve glycemic control and reduce heart failure morbidity. 1

3. Verify renal function before initiating SGLT2 inhibitor therapy and ensure metformin dosing remains appropriate for kidney function. 2

4. Monitor for volume status when initiating SGLT2 inhibitors, as they have diuretic effects that complement heart failure management. 1