Yes, prescribe an SGLT2 inhibitor immediately for this patient with HFrEF, regardless of diabetes status.
This patient with an ejection fraction of 25% has a clear indication for SGLT2 inhibitor therapy based on heart failure alone—the A1c of 6.4 (prediabetes range) is irrelevant to the decision. SGLT2 inhibitors are now core guideline-directed medical therapy for all patients with HFrEF (EF ≤40%), independent of glycemic status. 1
Primary Indication: Heart Failure with Reduced Ejection Fraction
SGLT2 inhibitors are Class I recommendations for HFrEF across all major guidelines, positioned as foundational therapy alongside ACE inhibitors/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists. 1
The 2022 AHA/ACC/HFSA guidelines explicitly recommend SGLT2 inhibitors for patients with HFrEF to reduce cardiovascular death and heart failure hospitalization. 1
The 2021 ESC guidelines designate SGLT2 inhibitors as "core treatments suitable for all patients" with HFrEF, not as add-on therapy. 1
Evidence Supporting Use Without Diabetes
The EMPEROR-Reduced trial demonstrated that empagliflozin reduced cardiovascular death or heart failure hospitalization by 25% in patients with HFrEF (EF ≤40%), with identical benefit in patients with and without diabetes (HR 0.72 vs 0.78, P-interaction=0.57). 2, 3
Among the 3,730 patients enrolled in EMPEROR-Reduced, 50% had diabetes, 34% had prediabetes (HbA1c 5.7-6.4%), and 16% had normoglycemia—empagliflozin's cardiovascular and renal benefits were consistent across all three groups. 2
Baseline HbA1c as a continuous variable did not modify treatment benefits (P-interaction=0.40), confirming that glycemic status is irrelevant to the heart failure indication. 2
Practical Prescribing for This Patient
Start empagliflozin 10 mg once daily or dapagliflozin 10 mg once daily immediately—these are the evidence-based doses that require no titration. 1, 4
Key advantages for initiation:
No blood pressure or heart rate effects, unlike other HFrEF medications, making initiation straightforward. 1
No dose titration required—the starting dose is the therapeutic dose. 1
Benefits accrue rapidly within days to weeks, not months, making early initiation critical. 1
Safe across a wide range of kidney function: empagliflozin down to eGFR ≥20 mL/min/1.73 m², dapagliflozin down to eGFR ≥25 mL/min/1.73 m². 1
Contraindications to verify:
- eGFR <20-30 mL/min/1.73 m² (depending on agent). 1
- Active diabetic ketoacidosis (not relevant here). 1
- History of serious hypersensitivity to the drug. 1
Clinical Context: Prediabetes (A1c 6.4)
This A1c of 6.4 represents prediabetes, not diabetes, but this distinction is clinically irrelevant for SGLT2 inhibitor prescribing in HFrEF. 2
SGLT2 inhibitors did not lower HbA1c in patients with prediabetes or normoglycemia in EMPEROR-Reduced and were not associated with hypoglycemia risk. 2
The 2024 DCRM guidelines note that SGLT2 inhibitors may be used "later in glucose hierarchy" when the primary indication is glycemic control, but when prescribed for HFrEF, glucose-lowering is a secondary consideration. 1
Timing: Initiate Now, Not Later
If this patient is hospitalized or recently hospitalized, initiate the SGLT2 inhibitor before discharge—deferring to outpatient follow-up results in >75% of patients never receiving the medication within the next year. 1
The ACC/AHA guidelines have an explicit Class I recommendation for in-hospital initiation of GDMT including SGLT2 inhibitors before discharge. 5
SGLT2 inhibitors are uniquely suited for in-hospital initiation due to rapid benefit onset, excellent safety profile, and no hemodynamic effects. 1
Recognizing that 1 in 4 patients hospitalized for HF die or are readmitted within 30 days, delaying SGLT2 inhibitor initiation exposes patients to excess risk of early clinical worsening and death. 1
Additional Cardiovascular and Renal Benefits
SGLT2 inhibitors reduce total heart failure hospitalizations by 30% (HR 0.70,95% CI 0.58-0.85) beyond just the first event. 3
Renal protection is substantial: empagliflozin slowed eGFR decline from -2.28 to -0.55 mL/min/1.73 m²/year and reduced serious renal outcomes. 3
Despite transient eGFR drops after initiation, long-term kidney function is preserved. 1
Common Pitfall to Avoid
Do not withhold SGLT2 inhibitors because the patient "doesn't have diabetes"—this reflects outdated thinking from when these drugs were only approved for glycemic control. The heart failure indication is now primary and diabetes-independent. 2, 3