How to adjust insulin regimen when switching from Insulatard (NPH insulin) to subcutaneous (s/c) glargine (insulin glargine) after introducing dapagliflozin (SGLT2 inhibitor)?

Switching from Insulatard (NPH) to Subcutaneous Glargine After Starting Dapagliflozin

When switching from Insulatard 40 units to subcutaneous glargine after initiating dapagliflozin, start glargine at 32 units once daily (80% of the NPH dose) and reduce the dose by an additional 10-20% (to approximately 28-32 units) to account for the glucose-lowering effect of dapagliflozin. 1, 2

Initial Dose Conversion Algorithm

Step 1: Calculate Base Glargine Dose

• Convert from once-daily NPH to glargine at the same dose (40 units) 1, 2
• However, since dapagliflozin is now on board, reduce the starting glargine dose by 20% to prevent hypoglycemia 1
• Starting glargine dose: 32 units once daily 1, 2

Step 2: Account for SGLT2 Inhibitor Effect

• Dapagliflozin reduces HbA1c by approximately 0.9-1.2% when added to insulin regimens 3, 4, 5
• The American College of Cardiology recommends reducing insulin doses by approximately 20% when adding SGLT2 inhibitors to prevent hypoglycemia 1
• Consider starting at 28-32 units of glargine once daily 1

Timing and Administration

• Administer glargine subcutaneously once daily at the same time each day (can be any time, but consistency is critical) 2
• Rotate injection sites within the same region (abdomen, thigh, or deltoid) to reduce lipodystrophy risk 2
• Do not mix or dilute glargine with any other insulin 2

Critical Monitoring Requirements

First 3-4 Weeks (Intensive Phase):

• Self-monitor blood glucose at least 3-4 times daily, including fasting and pre-meal readings 1, 6
• Check for hypoglycemia symptoms at every contact 7, 6
• Monitor for euglycemic ketoacidosis signs (nausea, vomiting, abdominal pain, dyspnea) even with normal glucose levels 8

Ongoing Monitoring:

• Assess adequacy of insulin dose at every visit 1
• Monitor blood pressure and weight (dapagliflozin typically reduces both) 4, 5
• Check renal function periodically, as dapagliflozin requires eGFR >30 mL/min/m² 1

Titration Strategy

Evidence-Based Titration Algorithm:

• Increase glargine by 2 units every 3 days to reach fasting plasma glucose goal without hypoglycemia 1
• Target fasting glucose: 4.4-7.2 mmol/L (80-130 mg/dL) 1
• If hypoglycemia occurs without clear cause, reduce dose by 10-20% 1

Expected Outcomes:

• Dapagliflozin addition typically results in 2-4.6 kg weight loss over 3-6 months 4, 5
• HbA1c reduction of 0.9-1.2% with dapagliflozin added to insulin 3, 4, 5
• Insulin dose stabilization or reduction (NPH doses often increase over time, whereas glargine with dapagliflozin remains stable) 9, 5

Critical Safety Considerations

Hypoglycemia Risk Reduction:

• The combination of glargine and dapagliflozin has significantly lower hypoglycemia rates than NPH-based regimens 1, 3
• Hypoglycemia risk with dapagliflozin is only 1.6% compared to 15.1% with insulin intensification alone 3
• If patient is on sulfonylureas, reduce dose by 50% or discontinue when adding dapagliflozin to insulin 1, 7

Euglycemic Ketoacidosis Prevention:

• Educate patient to never discontinue insulin during illness 8
• Pause dapagliflozin during acute illness, surgery, or periods of reduced oral intake 8
• Monitor blood or urine ketones when feeling unwell 8
• Maintain at least low-dose insulin even if glucose is well-controlled 8

Genital and Urinary Infections:

• Dapagliflozin increases risk of genital mycotic infections (7.4-14.3%) and UTIs (8.4-13.8%) 1, 9
• Most infections occur in first 24 weeks and respond to routine management 9
• Emphasize meticulous personal hygiene 1

Common Pitfalls to Avoid

Do Not:

• Use the full 40-unit NPH dose when converting to glargine with dapagliflozin on board (this ignores the glucose-lowering effect of the SGLT2 inhibitor) 1
• Administer glargine intravenously or via insulin pump 2
• Mix or dilute glargine with other insulins 2
• Dismiss symptoms of ketoacidosis because glucose appears normal (euglycemic DKA is a real risk with SGLT2 inhibitors) 8

Do:

• Ensure adequate hydration (dapagliflozin causes osmotic diuresis) 1
• Check renal function before starting dapagliflozin (contraindicated if eGFR <30 mL/min/m²) 1
• Educate about carrying fast-acting carbohydrates for hypoglycemia treatment 6
• Consider prescribing glucagon for emergency use 6

When to Reassess Strategy

Consider intensification if:

• HbA1c remains >1.5-2.0% above goal after 3 months 1
• Fasting glucose consistently above target despite titration 1
• Evidence of overbasalization (elevated bedtime-to-morning differential, postprandial hyperglycemia) 1

Next steps if inadequate control:

• Add GLP-1 receptor agonist (can use fixed-ratio combination like iGlarLixi if available) 1
• Consider adding prandial insulin with largest meal 1
• SGLT2 inhibitors and GLP-1 RAs can be used concomitantly for additive benefits 1