What are the suitable diabetes regimen options for an elderly male patient with a body mass index (BMI) of 26, large B cell lymphoma, chronic kidney disease (CKD) stage 3, impaired renal function, and chronic bacteriuria, currently taking metformin (Metformin) 500 mg twice daily and Farxiga (Dapagliflozin) 10 mg daily, and Lantus (Insulin glargine) 15 units, who refuses to take insulin at discharge and is about to start new chemotherapy?

Diabetes Regimen Options for Elderly Patient Refusing Insulin at Discharge

Immediate Action Required: Discontinue Farxiga Before Chemotherapy

Farxiga (dapagliflozin) must be stopped immediately in this patient due to CKD stage 3 (GFR 39), chronic bacteriuria, and upcoming chemotherapy. 1, 2

• SGLT2 inhibitors like Farxiga are not recommended for glycemic control when eGFR <45 mL/min/1.73 m² and are likely ineffective based on mechanism of action 2
• Farxiga significantly increases risk of urosepsis and pyelonephritis, which is particularly dangerous in a patient with chronic bacteriuria 2
• During chemotherapy and "sick days," SGLT2 inhibitors should be temporarily stopped due to volume depletion risk and increased infection susceptibility 1
• Farxiga should be withheld at least 3 days before major procedures or situations with prolonged fasting, which includes chemotherapy initiation 2

Metformin Dose Adjustment Required

Reduce metformin to maximum 1000 mg total daily dose (500 mg twice daily is acceptable) given GFR 39 mL/min/1.73 m² 1, 3

• Metformin can be continued at reduced doses when eGFR is 30-44 mL/min/1.73 m², but must be reduced from higher doses 1
• Metformin must be temporarily discontinued during chemotherapy if the patient develops vomiting, diarrhea, dehydration, or cannot maintain fluid intake 1
• Resume metformin at usual doses within 24-48 hours of eating and drinking normally after any sick day episode 1

Recommended Non-Insulin Regimen Options

Option 1: GLP-1 Receptor Agonist (Preferred)

Add a GLP-1 receptor agonist with proven cardiovascular benefit (semaglutide, dulaglutide, or liraglutide) to metformin 500 mg twice daily 1, 4, 5

• GLP-1 receptor agonists retain glucose-lowering potency even at GFR as low as 15 mL/min/1.73 m² and are safe in CKD stage 3 1
• These agents provide HbA1c reduction of 0.6-0.8% when added to metformin, with cardiovascular and renal protective benefits 1, 4
• GLP-1 receptor agonists cause weight loss rather than weight gain and have minimal hypoglycemia risk 4, 5
• No dose adjustment needed for renal function unless eGFR severely reduced 5
• Caution: Monitor for nausea/vomiting during chemotherapy; may need temporary discontinuation if patient cannot tolerate oral intake 1

Option 2: DPP-4 Inhibitor (Alternative if GLP-1 not tolerated)

Add sitagliptin or linagliptin to metformin 500 mg twice daily 1, 6, 7

• Sitagliptin requires dose reduction to 25 mg daily when eGFR 30-44 mL/min/1.73 m² 6, 7
• Linagliptin requires no dose adjustment for renal impairment and may be preferred 6
• DPP-4 inhibitors provide safe, effective glycemic control in advanced CKD with minimal hypoglycemia risk 1, 7
• Less potent than GLP-1 receptor agonists (HbA1c reduction ~0.5-0.7%) but better tolerated 1

Option 3: Repaglinide (If rapid-acting agent needed)

Add repaglinide to metformin if postprandial glucose control is problematic 6, 7

• Repaglinide may be used even in dialysis patients and requires no dose adjustment for renal impairment 6, 7
• Rapid- and short-acting mechanism reduces hypoglycemia risk compared to sulfonylureas 7
• Requires dosing with meals, which may be challenging during chemotherapy-related anorexia 7

Critical Sick Day Management During Chemotherapy

Provide written sick day medication guidance before discharge 1

When to Stop Medications Temporarily:

• Stop metformin if vomiting >4 times in 12 hours, cannot keep fluids down, or signs of dehydration develop 1
• Stop any remaining diuretics or antihypertensives if volume depleted 1
• Resume medications within 24-48 hours of eating and drinking normally 1

When to Seek Emergency Care:

• Reduced consciousness, new confusion, difficulty breathing, or fainting 1
• Fever >38°C on 2 measurements with signs of infection 1
• Persistent vomiting preventing medication or fluid intake for >72 hours 1

Monitoring Requirements

Check HbA1c in 3 months to assess treatment effectiveness 4, 5

• Monitor renal function every 3 months during chemotherapy, as nephrotoxic agents may further reduce GFR 1
• If eGFR drops below 30 mL/min/1.73 m², discontinue metformin entirely 1
• Monitor for urinary tract infections given chronic bacteriuria, especially if SGLT2 inhibitor was recently used 2
• Weekly fasting blood glucose monitoring during first month of new regimen 5

Important Caveats

This patient's glycemic targets should be individualized to 7.0-8.0% given elderly age, CKD stage 3, cancer diagnosis, and upcoming chemotherapy 1, 4

• Aggressive glycemic control (HbA1c <7.0%) increases hypoglycemia risk in elderly patients with CKD and limited life expectancy 4
• The combination of cancer, CKD, and chemotherapy constitutes multiple comorbidities warranting less stringent targets 1, 4
• Avoid overtreatment: simpler regimens reduce medication burden and hypoglycemia risk during cancer treatment 1