What are the guidelines, contraindications, and potential complications, such as Chronic Kidney Disease (CKD), for a patient with type 1 diabetes using the STLT 2 I (basal-bolus) insulin regimen?

SGLT2 Inhibitors in Type 1 Diabetes: Use, Contraindications, and Complications

Direct Answer

SGLT2 inhibitors are NOT recommended for routine use in type 1 diabetes patients on insulin, and their use should be avoided in the hospital setting due to significant risk of diabetic ketoacidosis (DKA). 1

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Critical Contraindications for SGLT2i Use

Absolute Contraindications

• Severe illness or critical medical conditions - SGLT2i must be avoided during acute illness 1
• Presence of ketonemia or ketonuria - immediate contraindication 1
• eGFR <30 ml/min/1.73 m² - SGLT2i are contraindicated and must be discontinued in advanced CKD 1
• End-stage renal disease (ESRD) on dialysis - absolute contraindication 2
• Prolonged fasting states - withhold SGLT2i during extended periods without food 1
• Surgical procedures - FDA mandates stopping SGLT2i 3 days before scheduled surgery (4 days for ertugliflozin) 1

Type 1 Diabetes-Specific Concerns

In type 1 diabetes, SGLT2 inhibitors carry a substantially elevated risk of euglycemic DKA - a life-threatening condition where ketoacidosis develops despite normal or near-normal blood glucose levels. 1 This occurs because:

• SGLT2i lower glucose without providing insulin
• Patients may reduce insulin doses inappropriately when seeing lower glucose readings
• Ketone production continues unchecked without adequate insulin

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Proper Insulin Management in Type 1 Diabetes

Basal-Bolus Regimen Requirements

All hospitalized patients with type 1 diabetes require an insulin regimen with both basal and correction components, with addition of prandial insulin if eating. 1

Why Basal-Bolus is Essential

• Sliding scale insulin alone is strongly discouraged and inadequate for type 1 diabetes 1
• Dosing insulin based solely on premeal glucose levels fails to account for basal insulin requirements or caloric intake, increasing risks of both hypoglycemia and hyperglycemia 1

Recommended Insulin Components

Basal Insulin:

• Typically dosed based on body weight 1
• Patients with renal insufficiency require lower doses due to decreased insulin clearance 1
• Long-acting analogues (glargine, degludec) are preferred over NPH insulin 3, 4, 5
• Glargine provides flat, peakless action profile lasting approximately 24 hours 4

Prandial (Bolus) Insulin:

• Rapid-acting insulin analogues (lispro, aspart, glulisine) administered 0-15 minutes before meals 6, 5
• Preferred over regular human insulin for better postprandial control and reduced late hypoglycemia 4, 5
• Insulin injections must align with meals 1

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How CKD Develops and Affects Insulin Management

Mechanisms of CKD Development

While the evidence provided focuses on management rather than pathogenesis, chronic hyperglycemia leads to microvascular damage in the kidneys through multiple pathways, resulting in progressive nephropathy and declining eGFR over years of poorly controlled diabetes. 1

Critical CKD-Related Insulin Adjustments

Hypoglycemia Risk Increases Dramatically:

• Approximately one-third of insulin degradation occurs in the kidneys 1
• Impaired kidney function prolongs insulin half-life 1
• Patients with type 1 diabetes and significant creatinine elevations (mean 2.2 mg/dL) have a 5-fold increase in severe hypoglycemia frequency 1
• Impaired renal gluconeogenesis with reduced kidney mass further compounds hypoglycemia risk 1

Monitoring Requirements:

• Patients must monitor glucose levels closely and reduce insulin doses as needed to avoid hypoglycemia 1
• HbA1c may be less reliable in ESRD due to reduced red blood cell lifespan, anemia, and hemoglobin carbamylation, though it remains useful for trending 2
• Target HbA1c of 7-8% (or 7-8.5%) for ESRD patients to minimize hypoglycemia risk 2

eGFR-Based Monitoring:

• eGFR ≥60: Monitor kidney function at least annually 1
• eGFR 45-59: Monitor at least every 3-6 months 1
• eGFR 30-44: Monitor at least every 3-6 months 1

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Additional Complications and Management

Hypoglycemia Prevention Protocol

Every hospital must adopt and implement a hypoglycemia management protocol with a prevention and treatment plan for each patient. 1

Key Predictors:

• 84% of patients with severe hypoglycemia (<40 mg/dL) had a prior episode of hypoglycemia (<70 mg/dL) during the same admission 1
• 78% of hypoglycemic episodes occurred in patients using basal insulin, peaking between midnight and 6 AM 1
• Despite recognition of hypoglycemia, 75% of patients did not have their basal insulin dose changed before the next administration 1

Acute Kidney Injury

Acute kidney injury is an important risk factor for hypoglycemia in the hospital, possibly due to decreased insulin clearance. 1

Genitourinary Infections (If SGLT2i Were Used)

• SGLT2i therapy increases genital mycotic infection risk (6% vs 1% on placebo) 7
• Most infections can be treated with standard antifungal therapy without discontinuing SGLT2i 7
• Discontinue SGLT2i immediately for severe infections or Fournier's gangrene 7
• Use cautiously in patients with recurrent or severe urinary tract infections 7

Medication Errors

Insulin is one of the most common drugs causing adverse events in hospitalized patients. 1 Common preventable sources include:

• Improper prescribing of glucose-lowering medications 1
• Inappropriate management of first hypoglycemia episode 1
• Nutrition-insulin mismatch from unexpected interruption of nutrition 1
• Accidental mix-ups between insulin products - instruct patients to check insulin labels before injection 3

Hypokalemia

Hypokalemia may be life-threatening - monitor potassium levels in at-risk patients and treat if indicated. 3

Weight Gain

Weight gain occurs with insulin therapy but is usually modest if basal insulin is begun appropriately before glycosuria has influenced calorie balance. 8 Patients should maintain waist size ≤40 inches (102 cm) for men and ≤35 inches (88.9 cm) for women. 1

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Transitioning from IV to Subcutaneous Insulin

When discontinuing intravenous insulin, administer subcutaneous basal insulin 2-4 hours before stopping the IV infusion. 1

Dosing calculation:

• Convert to basal insulin at 60-80% of the daily infusion dose 1
• Base the dose on insulin infusion rate during the last 6 hours when stable glycemic goals were achieved 1

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Metformin Considerations in CKD

Metformin dosing must be adjusted based on eGFR: 1

• eGFR <30: Stop metformin; do not initiate 1
• eGFR 30-44: Initiate at half the dose and titrate to half of maximum recommended dose 1
• eGFR 45-59: Initiate at half the dose and titrate upwards to half of maximum recommended dose 1
• Metformin is absolutely contraindicated in ESRD due to lactic acidosis risk 2