In a 75‑year‑old male with type 2 diabetes on metformin 1000 mg twice daily, admitted for chimeric antigen receptor T‑cell (CAR‑T) therapy, weight 80 kg, BMI 28, serum creatinine 1.54 mg/dL (eGFR ≈47 mL/min), who missed his metformin dose and now has fasting glucose ~135 mg/dL but post‑prandial glucose 259–288 mg/dL, should I start basal insulin glargine (Lantus) and use rapid‑acting insulin correction for hyperglycemia?

Immediate Insulin Management for CAR-T Therapy Patient with Acute Hyperglycemia

Yes, start basal insulin glargine (Lantus) immediately at 10 units once daily at bedtime, and implement a correction insulin protocol using rapid-acting insulin for pre-meal hyperglycemia. This patient's post-prandial glucose of 259–288 mg/dL with fasting values ~135 mg/dL indicates inadequate glycemic control that requires urgent intervention, especially in the context of CAR-T therapy where metabolic stress and infection risk are elevated.11

Critical Context: Metformin Contraindication

Metformin must remain discontinued during hospitalization for CAR-T therapy due to this patient's eGFR of 47 mL/min/1.73 m² (CKD stage 3a) and the acute illness setting.11 CAR-T therapy carries substantial risks of:

• Cytokine release syndrome with tissue hypoperfusion
• Acute kidney injury
• Sepsis and infection

All of these dramatically increase lactic acidosis risk when metformin is continued.11 The combination of baseline renal impairment (Cr 1.54, eGFR 47) plus acute hospitalization creates an absolute contraindication.1

Immediate Insulin Initiation Protocol

Basal Insulin (Lantus/Glargine)

• Start with 10 units subcutaneously once daily at bedtime (approximately 0.125 units/kg for this 80 kg patient).112
• This conservative starting dose accounts for:
  • Age 75 years (high-risk for hypoglycemia)2
  • eGFR 47 mL/min (reduced insulin clearance)2
  • Acute illness setting (variable insulin sensitivity)2

Titration Algorithm

• Increase by 2 units every 3 days if fasting glucose remains 140–179 mg/dL.12
• Increase by 4 units every 3 days if fasting glucose ≥180 mg/dL.12
• Target fasting glucose: 80–130 mg/dL (may liberalize to 100–150 mg/dL given age and acute illness).11

Correction Insulin Protocol (Carb Correction)

• Add 2 units rapid-acting insulin (lispro, aspart, or glulisine) for pre-meal glucose >250 mg/dL.12
• Add 4 units rapid-acting insulin for pre-meal glucose >350 mg/dL.12
• Administer 0–15 minutes before meals.12
• For current glucose values of 259–288 mg/dL, this translates to 2 units correction before each meal in addition to scheduled doses.12

Why Not Prandial Insulin Yet?

Do not initiate scheduled prandial insulin at this time because:

• Fasting glucose (~135 mg/dL) suggests basal insulin deficiency is the primary issue.11
• Post-prandial elevations (259–288 mg/dL) can initially be managed with correction doses while basal insulin is optimized.12
• Adding both basal and prandial insulin simultaneously in a 75-year-old with renal impairment increases hypoglycemia risk unnecessarily.12

Criteria to add scheduled prandial insulin:112

• Fasting glucose reaches target (80–130 mg/dL) but post-prandial glucose remains >180 mg/dL after 3–6 months
• Basal insulin dose approaches 0.5 units/kg/day (~40 units) without achieving glycemic targets
• Persistent need for correction doses (>2 units) at most meals

Monitoring Requirements

Glucose Monitoring

• Check fasting glucose daily to guide basal insulin titration.12
• Check pre-meal glucose before each meal to calculate correction doses.12
• Check bedtime glucose to assess overall daily pattern.12
• For hospitalized patients eating regular meals, minimum 4 checks daily (before each meal + bedtime).12

Safety Monitoring

• Daily assessment of renal function (Cr, eGFR) given baseline CKD and CAR-T therapy risks.2
• Monitor for hypoglycemia (glucose <70 mg/dL); if occurs, reduce basal insulin by 10–20% immediately.12
• Watch for signs of infection or cytokine release syndrome, which will dramatically alter insulin requirements.11

Special Considerations for CAR-T Therapy

Acute Illness Adjustments

• Insulin requirements may increase 40–60% during cytokine release syndrome or infection.12
• If glucose exceeds 300 mg/dL with symptoms (nausea, vomiting), check for ketones immediately.12
• Maintain glucose target of 140–180 mg/dL for hospitalized non-critically ill patients.11

Renal Impairment Considerations

• At eGFR 47 mL/min, insulin clearance is reduced by approximately 25–30%.2
• Use lower starting doses (0.1–0.25 units/kg/day) to prevent hypoglycemia.2
• Titrate conservatively with close monitoring.2
• If eGFR declines further during CAR-T therapy, reduce total daily insulin by 20–50% depending on severity.2

Critical Pitfalls to Avoid

• Do not use sliding-scale insulin as monotherapy—this reactive approach is condemned by all major diabetes guidelines and leads to dangerous glucose fluctuations.12
• Do not restart metformin during acute hospitalization with eGFR 47 mL/min and CAR-T therapy; lactic acidosis risk is prohibitive.11
• Do not delay insulin initiation when glucose consistently exceeds 250 mg/dL; prolonged hyperglycemia increases infection risk and impairs CAR-T cell function.11
• Never give rapid-acting insulin at bedtime as a sole correction dose—this markedly raises nocturnal hypoglycemia risk.12
• Do not continue escalating basal insulin beyond 0.5 units/kg/day (~40 units) without addressing post-prandial hyperglycemia with scheduled prandial insulin.12

Expected Clinical Outcomes

• Fasting glucose should stabilize at 100–130 mg/dL within 5–7 days with appropriate basal insulin titration.12
• Post-prandial glucose should improve to <180 mg/dL with correction insulin protocol.12
• If post-prandial glucose remains >180 mg/dL despite optimized basal insulin, transition to scheduled prandial insulin (start with 4 units before largest meal).12

Post-Discharge Planning

• Resume metformin only after:11
  • CAR-T therapy complications resolved
  • eGFR stable ≥45 mL/min for at least 48 hours
  • No ongoing infection or tissue hypoxia
  • Patient tolerating regular oral intake
• Continue basal insulin at discharge with clear titration instructions.12
• Arrange endocrinology follow-up within 1–2 weeks for insulin regimen optimization.134