What is the treatment for a 70-year-old patient with type 2 diabetes mellitus (T2DM) managed with metformin (biguanide) 1g twice daily, who has undergone thrombolysis for an acute left middle cerebral artery (MCA) ischemic stroke and is currently nil by mouth (NBM) with hyperglycemia?

Management of Hyperglycemia in Post-Thrombolysis Acute Stroke with Diabetes

Immediately discontinue metformin and initiate intravenous insulin therapy targeting blood glucose of 7.8-10 mmol/L (140-180 mg/dL), as this patient's CBG of 12.2 mmol/L exceeds the treatment threshold and metformin is contraindicated in the acute stroke setting due to NBM status and lactic acidosis risk. 1, 2

Immediate Actions

Discontinue Metformin

• Stop metformin immediately because the patient is nil by mouth (NBM), which creates a contraindication per FDA labeling: "Withholding of food and fluids during surgical or other procedures may increase the risk for volume depletion, hypotension, and renal impairment. Metformin hydrochloride tablets should be temporarily discontinued while patients have restricted food and fluid intake." 2
• The acute stroke setting with potential hypoxic states further contraindicates metformin: "Cardiovascular collapse (shock), acute myocardial infarction, sepsis, and other conditions associated with hypoxemia have been associated with lactic acidosis." 2

Initiate IV Insulin Protocol

• Start intravenous insulin immediately at the current glucose of 12.2 mmol/L (220 mg/dL), which exceeds the 10 mmol/L (180 mg/dL) treatment threshold recommended by the American Heart Association for critically ill stroke patients 1
• Use regular insulin at 1 unit/mL concentration with initial infusion rate of approximately 0.5 units/hour 1
• Target glucose range: 7.8-10 mmol/L (140-180 mg/dL) - this is the evidence-based range that balances glycemic control with hypoglycemia avoidance 3, 1

Monitoring Protocol

Glucose Monitoring Frequency

• Monitor blood glucose every 1-2 hours initially during the acute phase, particularly critical given this patient received thrombolysis 3, 1
• Patients with hyperglycemia who received rtPA have increased risk of symptomatic intracranial hemorrhage, making tight monitoring essential 3
• Adjust insulin infusion rate continuously to maintain target range 1

Critical Safety Threshold

• Never target normoglycemia or glucose <7.8 mmol/L (140 mg/dL) as this increases hypoglycemia risk without proven benefit 1
• Hypoglycemia (<3.3 mmol/L or 60 mg/dL) is particularly dangerous post-stroke and must be corrected urgently with 25 mL of 50% dextrose IV push if it occurs 3, 1

Evidence-Based Rationale

Why This Glucose Level Requires Treatment

• Hyperglycemia in acute stroke is strongly associated with worse outcomes, including increased infarct volume, higher mortality, and increased risk of hemorrhagic transformation 3, 1
• Among stroke patients treated with intravenous rtPA (as this patient was), hyperglycemia has been specifically associated with symptomatic intracranial hemorrhage and worse clinical outcomes 3
• The risk of hemorrhagic transformation increases by 75% per 100 mg/dL of blood glucose elevation 3

Why Not More Aggressive Targets

• The GIST-UK trial, the only randomized efficacy trial of hyperglycemia treatment in acute stroke, showed neutral results when targeting lower glucose levels 3
• Current evidence supports maintaining blood glucose in the range of 140-180 mg/dL (7.8-10 mmol/L) following American Diabetes Association recommendations for all hospitalized patients 3
• More aggressive glucose lowering requires intensive care unit admission for frequent monitoring and carries significant hypoglycemia risk without proven benefit 3

Transition Planning

When to Resume Oral Agents

• Once the patient can safely take oral intake and is neurologically stable, transition from IV insulin to subcutaneous insulin protocol 3
• Do not resume metformin until the patient has stable oral intake, normal renal function confirmed (eGFR >30 mL/min/1.73 m²), and no ongoing hypoxic states 2
• Metformin can be beneficial long-term: pre-stroke metformin use is associated with favorable functional outcomes (adjusted OR 1.94) and continuous metformin treatment before and after stroke improves 90-day outcomes 4, 5

Alternative Oral Agents if Metformin Contraindicated

• If metformin remains contraindicated due to renal impairment or other factors, consider DPP-4 inhibitors (minimal hypoglycemia risk, weight neutral) or SGLT2 inhibitors (cardiovascular benefits, though require eGFR monitoring) 6
• Sulfonylureas are effective alternatives but carry higher hypoglycemia risk in the post-stroke setting 3, 6

Common Pitfalls to Avoid

• Do not continue metformin in NBM patients - this is an explicit FDA contraindication that increases lactic acidosis risk 2
• Do not target glucose <140 mg/dL acutely - no evidence of benefit and increases dangerous hypoglycemia risk 3, 1
• Do not use subcutaneous insulin protocols initially - IV insulin allows rapid titration and is safer in the acute post-thrombolysis period 1
• Do not forget to check renal function before any future metformin restart, as stroke patients may develop acute kidney injury 2