What is the recommended treatment for an adult patient with type 2 diabetes mellitus (T2DM) who is at risk of or has developed heart failure, considering their current regimen and potential kidney function impairment?

Heart Failure Medications in Type 2 Diabetes

For adults with type 2 diabetes who are at risk of or have developed heart failure, SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin, or sotagliflozin) should be initiated immediately as foundational therapy, regardless of current glycemic control or baseline heart failure status. 1

Primary Medication Recommendations

SGLT2 Inhibitors: First-Line Therapy

SGLT2 inhibitors constitute the key treatment approach to reduce both cardiovascular disease and heart failure outcomes in people with diabetes, with robust evidence demonstrating consistent benefits across multiple large trials. 1

Prevention of Incident Heart Failure

• Empagliflozin reduced hospitalization for heart failure by 35% in the EMPA-REG OUTCOME trial, with benefits consistent regardless of prior heart failure history. 1

• Canagliflozin reduced heart failure hospitalization by 33% in the CANVAS Program and by 39% in the CREDENCE trial (in patients with diabetic kidney disease and albuminuria). 1

• Dapagliflozin reduced cardiovascular mortality and hospitalization for heart failure by 17% in DAPA-HF, with consistent benefits across all subgroups. 1

• Sotagliflozin (SGLT1/2 inhibitor) reduced the composite outcome of cardiovascular death, heart failure hospitalizations, and urgent heart failure visits in patients with type 2 diabetes, CKD, and cardiovascular risk in the SCORED trial. 1

Treatment of Established Heart Failure

For symptomatic heart failure (stage C and D), SGLT2 inhibitors provide mortality benefit in addition to standard guideline-directed medical therapy. 1

• Dapagliflozin 10 mg daily reduced the primary outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74,95% CI 0.65-0.85) in patients with HFrEF (ejection fraction ≤40%), regardless of diabetes status. 2

• Cardiovascular death was reduced by 18% (HR 0.82,95% CI 0.69-0.98), and all-cause mortality by 17% (HR 0.83,95% CI 0.71-0.97). 2

• Benefits were consistent in patients with and without diabetes, demonstrating glucose-independent cardioprotective mechanisms. 3, 2

Dosing Considerations for SGLT2 Inhibitors

Dapagliflozin dosing:

• 10 mg once daily is the universal dose for heart failure and cardiovascular protection, regardless of ejection fraction type or diabetes status. 4
• Can be initiated if eGFR ≥25 mL/min/1.73 m². 4
• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue 10 mg daily until dialysis is required. 4
• For glycemic control alone, do not initiate if eGFR <45 mL/min/1.73 m², though cardiovascular/renal benefits persist at lower eGFR levels. 4

Canagliflozin dosing:

• Maximum dose limited to 100 mg daily if eGFR is 30-44 mL/min/1.73 m². 5
• If eGFR <30 mL/min/1.73 m², initiation is not recommended, though may be continued at 100 mg daily if already started. 5

Finerenone: Add-On Therapy for Diabetic Kidney Disease

Finerenone is recommended in people with type 2 diabetes and diabetic kidney disease to reduce progression from stage A heart failure to symptomatic incident heart failure. 1

• In FIDELIO-DKD, finerenone reduced cardiovascular death, nonfatal MI, nonfatal stroke, or heart failure hospitalization by 13%, with only 7.7% of participants having prior heart failure history. 1

• In FIGARO-DKD, finerenone reduced the primary cardiovascular composite outcome (HR 0.87,95% CI 0.76-0.98, P=0.03). 1

• Finerenone provides complementary benefit to SGLT2 inhibitors in patients with diabetic kidney disease and albuminuria. 1

Beta-Blockers for Asymptomatic Left Ventricular Dysfunction

For patients with asymptomatic stage B heart failure (reduced LVEF <40%), beta-blockers provide mortality benefit:

• Carvedilol reduced mortality by 23% and heart failure hospitalization by 14% in the CAPRICORN study (23% had diabetes). 1

• Metoprolol improved adverse cardiac remodeling in asymptomatic individuals with LVEF <40% in the REVERT trial (45% had diabetes). 1

Integration with Current Regimen

When adding SGLT2 inhibitors to existing therapy:

• With sulfonylureas: Monitor closely for hypoglycemia; sulfonylurea dose reduction may be necessary. 5

• With insulin: Maintain at least low-dose insulin even during sick days when SGLT2 inhibitor is held to prevent diabetic ketoacidosis. 4

• With metformin and DPP-4 inhibitors (sitagliptin): No dose adjustments required; combination has low hypoglycemia risk. 4, 6

• With diuretics: Consider reducing diuretic doses when initiating SGLT2 inhibitors to prevent excessive volume depletion, especially in elderly patients. 4

Renal Function Considerations

SGLT2 inhibitors provide cardiovascular and renal protection even with impaired kidney function:

• Glucose-lowering efficacy decreases with declining renal function, but cardiovascular and renal benefits are preserved at lower eGFR levels. 4

• An initial eGFR dip of 3-5 mL/min/1.73 m² within 1-4 weeks is expected and reversible; this does not indicate harm. 4

• Check eGFR within 1-2 weeks after initiation; if eGFR decreases >30% from baseline with signs of hypovolemia, reduce diuretics first before adjusting SGLT2 inhibitor. 4

• Do not discontinue SGLT2 inhibitors solely because eGFR falls below 45 mL/min/1.73 m², as cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 4

Critical Safety Precautions

Sick day management (essential patient education):

• Withhold SGLT2 inhibitors during acute illness, particularly with fever, vomiting, diarrhea, or reduced oral intake. 4

• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 4

• Monitor for euglycemic diabetic ketoacidosis (DKA), which can occur even with normal blood glucose levels; check ketones if patients develop malaise, nausea, or vomiting. 4

Volume depletion risk:

• Assess volume status before initiating SGLT2 inhibitors and correct any depletion. 4

• Elderly patients and those on concurrent diuretics are at higher risk for volume depletion. 4

Genital mycotic infections:

• Occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo. 4

• Educate patients on daily hygienic measures to reduce risk. 4

Symptomatic Heart Failure: Collaborative Approach

For advanced symptomatic heart failure (stage C and D), guideline-directed medical therapy should follow 2022 AHA/ACC/HFSA guidelines, with cardiovascular specialist collaboration recommended. 1

• SGLT2 inhibitors should be initiated early as foundational therapy alongside ACE inhibitors/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists. 4

• Goal is to achieve optimal guideline-directed medical therapy within 3-6 months of heart failure diagnosis. 4

Common Pitfalls to Avoid

• Do not delay SGLT2 inhibitor initiation waiting for "optimal" glycemic control; cardiovascular benefits are glucose-independent. 1, 2

• Do not discontinue SGLT2 inhibitors when eGFR declines below 45 mL/min/1.73 m² if already initiated; continue for cardiovascular/renal protection. 4

• Do not use SGLT2 inhibitors for glycemic control alone when eGFR <45 mL/min/1.73 m², but continue for cardiovascular/renal protection down to eGFR 25 mL/min/1.73 m². 4

• Do not forget sick day rules; failure to withhold during acute illness significantly increases DKA risk. 4