Which of the following is considered a benefit of sodium‑glucose cotransporter‑2 (SGLT2) inhibitors such as canagliflozin?

SGLT2 Inhibitors: Cardiovascular and Heart Failure Benefits

SGLT2 inhibitors such as canagliflozin provide significant benefits in heart failure and cardiovascular disease, reducing heart failure hospitalizations by 27-39% and cardiovascular death by 13-38% across multiple large trials, regardless of diabetes status. 1

Primary Cardiovascular Benefits

The most compelling benefit of SGLT2 inhibitors is their robust effect on heart failure outcomes:

• Empagliflozin reduced heart failure hospitalizations by 35% and cardiovascular death by 38% in the EMPA-REG OUTCOME trial. 2
• Canagliflozin lowered heart failure hospitalizations by 33% in the CANVAS program and by 39% in the CREDENCE trial. 1, 2
• Dapagliflozin decreased the composite of worsening heart failure or cardiovascular death by 26% in DAPA-HF, with benefits occurring within weeks of initiation. 2

These benefits extend beyond diabetic patients—SGLT2 inhibitors reduce cardiovascular death and heart failure events in patients with HFrEF (LVEF ≤40%) regardless of diabetes status. 1

Cardiovascular Disease Risk Reduction

In patients with established atherosclerotic cardiovascular disease, SGLT2 inhibitors with demonstrated benefit (empagliflozin, canagliflozin, dapagliflozin) are recommended to reduce major adverse cardiovascular events. 1, 3

• Empagliflozin, canagliflozin, and dapagliflozin significantly reduced 3-point MACE (cardiovascular death, myocardial infarction, or stroke) in high-risk populations. 1
• The cardiovascular benefits are consistent across patients with and without prior heart failure, appearing much earlier than would be expected from anti-atherosclerotic effects alone. 4

Renal Protection

All SGLT2 inhibitor studies demonstrated protection against progression of diabetic kidney disease, with CREDENCE showing a 30% reduction in cardio-renal endpoints. 1

• Dapagliflozin reduced the risk of sustained eGFR decline, end-stage kidney disease, and cardiovascular death by 39% in the DAPA-CKD trial, even in non-diabetic patients. 2
• These agents can be used with eGFR as low as 20-30 mL/min/1.73m² for dapagliflozin, with benefits most pronounced when baseline renal function is impaired. 2, 5

Addressing the Multiple Choice Options

❌ Decrease in fungal UTIs

This is incorrect—SGLT2 inhibitors actually increase the risk of genital mycotic infections (1.5-1.7%) and urinary tract infections (2.3-2.7%), not decrease them. 2

✅ Benefits in Heart Failure or Cardiovascular Disease

This is the correct answer. The evidence is overwhelming and consistent across all major trials. 1, 2

❌ Extensive decrease in hemoglobin A1c

While SGLT2 inhibitors do lower A1c, the reduction is modest (typically 0.5-1.0%), not "extensive." 1 GLP-1 receptor agonists are described as "arguably the most effective glucose lowering medications," not SGLT2 inhibitors. 1

❌ Effective as monotherapy

SGLT2 inhibitors are not recommended as monotherapy for type 2 diabetes. Guidelines emphasize their use in combination with other agents, particularly in patients with established cardiovascular disease or heart failure. 1, 3

Important Safety Considerations

Monitor for euglycemic diabetic ketoacidosis, though this risk is significantly lower in non-diabetic populations. 2, 3

• Volume depletion may occur in approximately 5.7% of patients, especially those already on diuretics or with low blood pressure. 2, 6
• A mild, transient eGFR decline after initiation is expected and provides long-term kidney protection—do not discontinue the medication for this reason. 2
• Genital mycotic infections and UTIs are manageable adverse effects that should not preclude use in appropriate patients. 2

Clinical Implementation

Initiate SGLT2 inhibitors in all eligible patients with HFrEF (LVEF ≤40%) with NYHA class II-IV symptoms, regardless of diabetes status. 2

For patients with type 2 diabetes and established atherosclerotic cardiovascular disease, prescribe an SGLT2 inhibitor with proven cardiovascular benefit (empagliflozin, canagliflozin, or dapagliflozin) to reduce MACE and heart failure hospitalizations. 1, 3

SGLT2 inhibitors require no dose titration and have minimal effects on blood pressure, heart rate, or potassium levels, making them safe to combine with other guideline-directed medical therapy. 2