What is the optimal diabetes management strategy for an 82-year-old patient with impaired renal function, heart failure with reduced ejection fraction, and elevated FBS, currently taking Glipizide, Metformin, and Jardiance (Empagliflozin)?

Medication Adjustment Required: Discontinue Metformin and Optimize Empagliflozin

You must discontinue metformin immediately due to the GFR of 40 mL/min/1.73 m², as it is contraindicated below 30 mL/min/1.73 m² and should be reduced or withdrawn when eGFR is less than 45 mL/min/1.73 m² 1. Continue Jardiance (empagliflozin) 10 mg as it provides critical cardiovascular and renal protection in heart failure with reduced ejection fraction, even at this level of renal function 1.

Immediate Medication Changes

Discontinue Metformin

• Metformin accumulates with reduced kidney function and increases lactic acidosis risk, though absolute risk remains low 1
• The KDIGO 2020 guidelines specify metformin should be withdrawn when eGFR is less than 30 mL/min/1.73 m² or reduced when eGFR is less than 45 mL/min/1.73 m² 1
• At GFR 40, this patient falls into the category requiring dose reduction at minimum, but given the complexity of heart failure management, discontinuation is safer 1

Continue and Prioritize Empagliflozin (Jardiance)

• SGLT2 inhibitors like empagliflozin should be maintained as they have the least impact on blood pressure while providing mortality benefits in HFrEF 1
• Cardiovascular and kidney benefits persist even when eGFR is as low as 30-44 mL/min/1.73 m², despite reduced glucose-lowering efficacy 1
• The EMPEROR-Reduced trial confirmed benefits for heart failure with reduced ejection fraction, with over 80% of participants receiving RAS inhibitors 1
• Empagliflozin reduces cardiovascular death or hospitalization for heart failure by 29% (HR 0.71 [95% CI 0.55-0.92]) 1
• At eGFR >20 mL/min/1.73 m², empagliflozin can be continued for cardiovascular and renal protection 1, 2

Reassess Glipizide

• Sulfonylureas like glipizide should be avoided or used only if unable to achieve adequate glycemic control with alternative options in patients with HFrEF 1
• Glipizide increases hypoglycemia risk, particularly when combined with SGLT2 inhibitors 1
• Consider discontinuing glipizide given the patient's age (82 years), heart failure, and elevated FBS despite triple therapy 1

Glycemic Control Strategy

If FBS Remains Elevated After Metformin Discontinuation

Add a GLP-1 receptor agonist as the preferred next agent 1:

• GLP-1 RAs (liraglutide, semaglutide, dulaglutide) reduce cardiovascular events and can be used with eGFR >30 mL/min/1.73 m² 1, 2
• They have low hypoglycemia risk and promote weight loss of 2-4 kg 1
• GLP-1 RAs show beneficial effects on cardiovascular outcomes, though no effect on heart failure hospitalization 1
• Avoid GLP-1 RAs if recent heart failure decompensation 1

Alternative: Basal insulin if GLP-1 RA contraindicated 2:

• Insulin remains effective regardless of kidney function and can be dose-adjusted based on clinical response 2
• However, insulin should be considered only if unable to achieve adequate glycemic control with alternative options 1

Heart Failure Management Considerations

Monitor for Volume Status and Blood Pressure

• Empagliflozin may cause modest volume contraction, blood pressure reduction, and weight loss 1, 3
• Volume depletion events (hypotension, dehydration, hypovolemia) occurred in 0.5% of patients on empagliflozin 10 mg 3
• For patients at risk for hypovolemia due to concomitant diuretic use, consider decreasing the diuretic dose 1

Expected Renal Function Changes

• SGLT2 inhibitors may cause a modest reduction in eGFR within the first few weeks that is hemodynamic in nature and reversible 1
• This is not a reason to discontinue therapy, as long-term eGFR preservation has been reported with continuation 1
• Even when eGFR falls below 30 mL/min/1.73 m², SGLT2 inhibitors may be continued as long as they are well-tolerated and kidney replacement therapy is not imminent 1

Optimize Other Heart Failure Medications

• SGLT2 inhibitors and MRAs have the least effect on BP and should be maintained when possible during medication adjustments 1
• If symptomatic hypotension develops, reduce ACEi/ARB/ARNi first if heart rate >70 bpm, or reduce beta-blockers first if heart rate <60 bpm 1
• Close follow-up within 1-2 weeks of medication changes is recommended, with monitoring of blood pressure, heart rate, renal function, and electrolytes 4

Monitoring Plan

Short-term (1-2 weeks after metformin discontinuation):

• Assess fasting blood glucose and symptoms of hyperglycemia 1
• Monitor blood pressure, heart rate, and volume status 1, 4
• Check serum creatinine, eGFR, and potassium 1, 5

Ongoing monitoring:

• Assess for genital mycotic infections (4.1% with empagliflozin 10 mg) and urinary tract infections 3
• Monitor for diabetic ketoacidosis, though risk is low 1, 3
• Vitamin B12 levels if metformin was used long-term (>4 years) 1

Common Pitfalls to Avoid

• Do not discontinue empagliflozin due to modest eGFR decline in first few weeks - this is hemodynamic and reversible 1
• Do not reduce or discontinue SGLT2 inhibitors for asymptomatic or mildly symptomatic low BP - this could compromise long-term outcomes 1
• Do not continue metformin at GFR 40 without dose reduction at minimum - accumulation risk increases 1
• Do not add insulin as first-line therapy - GLP-1 RAs are preferred for cardiovascular benefits 1, 2