Can an SGLT‑2 inhibitor be initiated in a patient with heart failure with reduced ejection fraction and chronic liver disease who has an estimated glomerular filtration rate of 25 mL/min and a serum bicarbonate of 15 mEq/L?

SGLT-2 Inhibitor Initiation in HFrEF with eGFR 25 mL/min and Severe Metabolic Acidosis

Do not start an SGLT-2 inhibitor in this patient until the severe metabolic acidosis (bicarbonate 15 mEq/L) is corrected. While the eGFR of 25 mL/min falls within the acceptable range for SGLT-2 inhibitor initiation in heart failure, the profound metabolic acidosis represents a critical contraindication that must be addressed first.

Primary Concern: Ketoacidosis Risk

The serum bicarbonate of 15 mEq/L indicates severe metabolic acidosis. SGLT-2 inhibitors carry a well-documented risk of euglycemic diabetic ketoacidosis, and initiating therapy in a patient with pre-existing severe acidosis substantially amplifies this risk 1, 2. The KDIGO guidelines explicitly recommend withholding SGLT-2 inhibitors during critical medical illness when patients are at greater risk for ketosis 1.

eGFR Considerations

From a renal function standpoint alone, the eGFR of 25 mL/min would technically permit SGLT-2 inhibitor initiation:

• KDIGO 2024 guidelines provide a strong (1A) recommendation for SGLT-2 inhibitors in heart failure patients with eGFR ≥20 mL/min/1.73 m², irrespective of albuminuria level 1
• The threshold was lowered from ≥30 to ≥20 mL/min based on accumulating evidence from trials like DAPA-CKD 3
• Once initiated, SGLT-2 inhibitors can be continued even if eGFR falls below 20 mL/min until dialysis initiation 1, 2

However, the eGFR threshold assumes metabolic stability, which this patient clearly lacks.

Clinical Algorithm for This Patient

Step 1: Correct the metabolic acidosis first

• Investigate and treat the underlying cause (uremic acidosis likely given eGFR 25, but consider other contributors)
• Target bicarbonate >22 mEq/L before considering SGLT-2 inhibitor initiation
• KDIGO 2024 recommends pharmacological treatment with or without dietary intervention for metabolic acidosis in CKD 1

Step 2: Reassess metabolic stability

• Ensure patient is not in a catabolic state
• Confirm adequate oral intake
• Verify absence of intercurrent illness

Step 3: Initiate SGLT-2 inhibitor only after metabolic correction

• Once bicarbonate normalized and patient metabolically stable
• Provide comprehensive sick-day protocol education emphasizing temporary discontinuation during illness, fasting, or reduced oral intake 1, 2
• Monitor for signs/symptoms of ketoacidosis (nausea, vomiting, abdominal pain, fatigue) even with normal glucose levels

Chronic Liver Disease Consideration

The chronic liver disease adds complexity but is not an absolute contraindication. However, it may contribute to:

• Impaired lactate clearance (relevant if considering other medications)
• Altered volume status requiring careful monitoring
• Potential nutritional deficiencies and catabolic state

The liver disease itself does not preclude SGLT-2 inhibitor use once metabolic acidosis is corrected, as these agents have not been adequately studied but are not specifically contraindicated in liver disease 2.

Critical Pitfall to Avoid

The most dangerous error would be initiating an SGLT-2 inhibitor based solely on meeting the eGFR threshold while ignoring the severe metabolic acidosis. This patient's bicarbonate of 15 mEq/L represents a metabolic emergency that supersedes the cardiovascular and renal benefits of SGLT-2 inhibitor therapy. The risk of precipitating life-threatening ketoacidosis in this acidotic state far outweighs any benefit from early SGLT-2 inhibitor initiation.

Monitoring After Eventual Initiation

Once acidosis is corrected and SGLT-2 inhibitor initiated:

• The expected initial eGFR dip (typically 3-5 mL/min) is not an indication to discontinue therapy 1, 2
• Monitor volume status given concurrent diuretic use likely in HFrEF
• Regular bicarbonate monitoring given baseline acidosis tendency
• Blood or urine ketone monitoring if any concerning symptoms develop 3, 2

In summary: Correct the bicarbonate to >22 mEq/L first, ensure metabolic stability, then initiate the SGLT-2 inhibitor with appropriate safety monitoring and patient education.