Should diabetic medications be discontinued before chemotherapy?

Management of Diabetic Medications Before Chemotherapy

Do not routinely discontinue diabetic medications before chemotherapy; instead, optimize glycemic control pre-treatment and adjust medications based on the specific chemotherapy regimen, particularly when glucocorticoids like dexamethasone are involved. 1

Pre-Chemotherapy Assessment and Optimization

All patients with diabetes should achieve optimized glycemic control before initiating chemotherapy treatment. 2 This is critical because:

• Hyperglycemia during chemotherapy occurs in 10-30% of patients and is associated with increased toxicity, poor prognosis, and extended hospital stays 2, 3
• Patients with baseline dysglycemia (prediabetes or diabetes) spend significantly more time hyperglycemic during treatment—73.3% of time for those with diabetes versus 3.9% for euglycemic patients 4
• Assessing hypoglycemia risk is mandatory before starting chemotherapy, as many patients require medication reduction rather than continuation of their full regimen 5

Medication Adjustments Based on Chemotherapy Type

For Glucocorticoid-Containing Regimens (Most Common)

When chemotherapy includes dexamethasone or other glucocorticoids, anticipate afternoon and evening hyperglycemia and adjust medications proactively: 1

• For patients without diabetes who develop two blood glucose readings >250 mg/dL (13.9 mmol/L): Initiate multiple-dose insulin therapy at 1-1.2 U/kg per day, distributed as 25% basal and 75% prandial 1
• For patients with existing diabetes on insulin: Add NPH insulin (0.1-0.3 U/kg per day) to the usual regimen, with doses determined by steroid dose and oral intake 1
• Sulfonylureas should NOT be used in this clinical scenario due to unpredictable hypoglycemia risk 1

Specific Medication Considerations

Metformin:

• Continue metformin if eGFR ≥30 mL/min/1.73 m² 1
• Temporarily discontinue before procedures with iodinated contrast, during hospitalizations, or when acute illness may compromise renal or liver function 1
• Monitor for gastrointestinal side effects that may worsen with chemotherapy-induced nausea 1

Sulfonylureas:

• Reduce dose or discontinue due to high hypoglycemia risk, especially when combined with chemotherapy-induced anorexia or nausea 1
• Many antimicrobials used during chemotherapy (fluoroquinolones, sulfamethoxazole-trimethoprim) interact with sulfonylureas to precipitate hypoglycemia 1

SGLT2 Inhibitors:

• Continue for cardiovascular and renal benefits unless contraindicated 1
• Monitor closely for diabetic ketoacidosis risk, particularly with reduced oral intake 1

GLP-1 Receptor Agonists:

• Generally continue for cardiovascular benefits 1
• May need dose reduction if chemotherapy-induced nausea is severe 1

Monitoring Strategy During Chemotherapy

Implement intensive glucose monitoring rather than medication discontinuation: 2, 5

• Blood glucose monitoring should occur in all patients receiving continuous oral corticosteroids as part of chemotherapy 6
• Continuous glucose monitoring (CGM) in blinded mode is highly recommended to identify hypoglycemia patterns and guide medication adjustments 5
• In one study, 51.9% of patients required reduction (not discontinuation) of antidiabetic treatment after CGM-guided assessment, with significant reduction in time spent hypoglycemic 5

Critical Pitfalls to Avoid

Never discontinue all diabetic medications prophylactically before chemotherapy. This approach is not supported by guidelines and may lead to:

• Uncontrolled hyperglycemia that worsens chemotherapy tolerance and outcomes 2, 3
• Missed opportunity to optimize control before treatment-induced metabolic stress 4

Do not continue aggressive sulfonylurea therapy when starting glucocorticoid-containing chemotherapy, as this combination dramatically increases hypoglycemia risk 1

Avoid therapeutic inertia—reassess medications at every visit during chemotherapy, as needs change rapidly with treatment cycles, oral intake variations, and steroid dosing 1

Practical Algorithm for Decision-Making

1. Pre-chemotherapy (2-4 weeks before):

   • Assess baseline A1c and current glucose control 2
   • Evaluate hypoglycemia risk with current regimen 5
   • Consider CGM to identify patterns 5
   • Optimize control but reduce or stop sulfonylureas if glucocorticoids will be used 1

2. At chemotherapy initiation:

   • Continue metformin (if eGFR adequate), SGLT2 inhibitors, and GLP-1 RAs 1
   • Add or increase insulin if glucocorticoids are part of regimen 1
   • Discontinue or reduce sulfonylureas 1

3. During treatment cycles:

   • Monitor glucose before each cycle 6
   • Adjust insulin doses with steroid cycles 1
   • Rapidly reduce insulin when dexamethasone is stopped 1

4. For treatment-emergent hyperglycemia:

   • Initiate insulin therapy as first-line for glucocorticoid-induced hyperglycemia 1
   • Target fasting glucose 90-150 mg/dL (5.0-8.3 mmol/L) 1

The key principle is medication adjustment and optimization, not blanket discontinuation, with the specific approach determined by the chemotherapy regimen's metabolic effects. 1, 2