What is the optimal management for an adult with type 2 diabetes and chronic heart failure with reduced ejection fraction?

Best Treatment for Diabetic with Heart Failure

An SGLT2 inhibitor with proven cardiovascular benefit is the cornerstone treatment for patients with type 2 diabetes and heart failure, regardless of ejection fraction status, and should be initiated immediately alongside standard heart failure therapies. 1

Primary Pharmacologic Approach

SGLT2 Inhibitors: First-Line Therapy

For patients with type 2 diabetes and established heart failure (either HFrEF or HFpEF), an SGLT2 inhibitor is recommended to reduce the risk of worsening heart failure and cardiovascular death. 1 This recommendation carries the highest level of evidence (Grade A) and applies equally to both reduced and preserved ejection fraction. 1

• SGLT2 inhibitors also improve symptoms, physical limitations, and quality of life in this population. 1
• The cardiovascular benefit is independent of glycemic control, so initiation should not be delayed based on HbA1c levels. 2
• These agents work through glucose-independent mechanisms and reduce heart failure hospitalizations by approximately 30%. 3
• SGLT2 inhibitors are safe and effective even with severe renal impairment (eGFR down to 20-25 mL/min/1.73 m²), requiring no dose adjustment. 4, 2

Guideline-Directed Medical Therapy for Heart Failure

The following medications should be used in conjunction with SGLT2 inhibitors:

ACE Inhibitors or ARBs:

• Recommended for patients with diabetes and established ASCVD or age ≥55 years with additional cardiovascular risk factors to reduce cardiovascular events and mortality. 1
• In asymptomatic stage B heart failure, ACE inhibitors or ARBs are recommended to prevent progression to symptomatic heart failure. 1
• When eGFR <30 mL/min/1.73 m², use ACE inhibitors or ARBs instead of ARNI (sacubitril/valsartan), with careful monitoring of renal function and potassium. 4

Beta-Blockers:

• Use evidence-based beta-blockers (bisoprolol, carvedilol, or sustained-release metoprolol succinate) and titrate to target or maximally tolerated dose. 4
• In asymptomatic stage B heart failure, beta-blockers prevent progression to symptomatic disease. 1
• For patients with prior myocardial infarction, continue beta-blockers for at least 3 years post-event. 1
• Treatment of HFrEF should include a beta-blocker with proven cardiovascular outcomes benefit unless contraindicated. 1

Mineralocorticoid Receptor Antagonists (MRAs):

• For patients with CKD and albuminuria on maximum tolerated ACE inhibitor or ARB doses, add a nonsteroidal MRA (finerenone) to improve cardiovascular outcomes and reduce CKD progression. 1
• Traditional guidelines recommend MRAs only if eGFR >30 mL/min/1.73 m² and potassium <5.0 mEq/L, but recent evidence shows effectiveness even when eGFR declines below 30. 4

Additional Therapeutic Considerations

GLP-1 Receptor Agonists

For patients with type 2 diabetes, obesity, and symptomatic HFpEF, a GLP-1 RA with demonstrated benefit is recommended to reduce heart failure-related symptoms, physical limitations, and improve exercise function. 1

• In patients with established ASCVD or multiple risk factors, combined therapy with an SGLT2 inhibitor and GLP-1 RA may provide additive reduction in cardiovascular and kidney events. 1, 2

Metformin Safety

• Metformin may be continued for glucose lowering if eGFR remains >30 mL/min/1.73 m² in patients with stable heart failure. 1
• Avoid metformin in unstable or hospitalized patients with heart failure and when eGFR <30 mL/min/1.73 m² due to lactic acidosis risk. 1, 4

Diuretic Management

• Use loop diuretics as needed to control congestion. 4
• SGLT2 inhibitors enhance diuretic efficacy and may reduce the need for loop diuretic intensification. 4

Implementation Strategy

Start all four medication classes (SGLT2 inhibitor, beta-blocker, ACE inhibitor/ARB, and MRA if appropriate) simultaneously at low doses rather than sequential uptitration, prioritizing SGLT2 inhibitors and beta-blockers first. 4

Monitoring Protocol

• Check potassium and renal function weekly for the first 2-4 weeks after initiating or uptitrating therapy, then every 2 weeks until stable. 4
• Monitor for hyperkalemia when using MRAs or ARBs. 5

Interprofessional Approach

• For patients with asymptomatic stage B heart failure, optimize guideline-directed medical therapy through an interprofessional approach that includes a cardiovascular disease specialist. 1

Critical Pitfalls to Avoid

Do not withhold SGLT2 inhibitors due to low eGFR—they are safe and effective down to eGFR 20 mL/min/1.73 m². 4

• Do not delay SGLT2 inhibitor initiation based on inadequate glycemic control; the cardiovascular indication is independent of HbA1c. 2
• Do not automatically apply HFrEF treatment algorithms to HFpEF patients, as the pathophysiology and evidence base differ. 5
• Avoid routine use of nitrates or phosphodiesterase-5 inhibitors in HFpEF as they are ineffective. 5
• Do not perform routine screening for coronary artery disease in asymptomatic patients, as it does not improve outcomes when ASCVD risk factors are treated. 1

Ejection Fraction-Specific Considerations

Heart Failure with Reduced Ejection Fraction (HFrEF)

• The combination of SGLT2 inhibitor and ARNI (sacubitril/valsartan) is well-tolerated and associated with lower risk of heart failure hospitalization. 6
• ARNI is FDA-approved to reduce cardiovascular death and hospitalization in chronic heart failure with LVEF below normal. 7

Heart Failure with Preserved Ejection Fraction (HFpEF)

• SGLT2 inhibitors are first-line therapy (Class 2a recommendation) to decrease heart failure hospitalizations and cardiovascular mortality. 5
• Beta-blockers may be beneficial in specific HFpEF patients with coronary artery disease, atrial fibrillation requiring rate control, hypertension, or tachycardia. 5
• ARBs have weak evidence (Class 2b) for selected HFpEF patients; ACE inhibitors lack strong evidence specifically for HFpEF. 5