What is the best course of action for a male patient with diabetes mellitus type II, hypertension, and hyperlipidemia, who has shown an increase in Hemoglobin A1c (HbA1c) from 9.6% to 10.2% despite reported compliance with his current medication regimen of Farxiga (dapagliflozin) 10 mg once a day, metformin 1000 mg twice a day, and Basaglar (insulin glargine) 68 units subcutaneously (SQ) once a day?

Immediate Treatment Intensification Required

This patient requires immediate intensification of his diabetes regimen by adding a GLP-1 receptor agonist to his current therapy and aggressively titrating his basal insulin dose. 1, 2

Current Status Assessment

The patient's HbA1c has worsened from 9.6% to 10.2% over six months despite reported medication compliance, indicating treatment failure. 1 His current regimen includes:

• Basaglar (insulin glargine) 68 units daily
• Metformin 1000 mg twice daily
• Farxiga (dapagliflozin) 10 mg daily

The basal insulin dose of 68 units is likely insufficient and requires aggressive titration. 2, 3 For an HbA1c >10%, the American Diabetes Association recommends starting doses of 0.3-0.5 units/kg/day as total daily insulin. 4 This patient needs both increased basal coverage and likely prandial insulin coverage given the severity of hyperglycemia. 1, 2

Immediate Action Plan

1. Add a GLP-1 Receptor Agonist

Add a GLP-1 receptor agonist immediately to the current regimen. 1, 2 Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease or indicators of high cardiovascular risk, a GLP-1 receptor agonist is preferred and provides superior HbA1c reduction compared to insulin intensification alone. 1 The combination of metformin, basal insulin, and a GLP-1 receptor agonist addresses multiple pathophysiologic defects while minimizing hypoglycemia risk and weight gain. 4, 5

GLP-1 receptor agonists can provide HbA1c reductions of 0.6-0.8% when added to existing therapy and offer cardiovascular protection. 2 Studies show that at baseline HbA1c of 10%, GLP-1 receptor agonists produce HbA1c reductions of 1.9-2.5%, often superior to insulin glargine alone. 5

2. Aggressively Titrate Basal Insulin

Increase Basaglar by 4 units every 3 days until fasting glucose reaches 80-130 mg/dL. 2, 3 For patients with HbA1c ≥10%, aggressive titration with 4-unit increments is appropriate rather than the standard 2-unit increments. 4, 3

The current dose of 68 units may be approaching the threshold where prandial insulin becomes necessary (typically 0.5 units/kg/day). 2, 3 However, before adding prandial insulin, optimize basal coverage and add the GLP-1 receptor agonist first. 2

3. Optimize Metformin Dosing

Increase metformin to 2000 mg daily (1000 mg twice daily is already being taken, but verify compliance and consider increasing to 2500 mg if tolerated). 4 Metformin should remain the foundation of therapy and be continued when intensifying insulin. 1, 4 The maximum effective dose is up to 2500 mg/day. 4

4. Continue Farxiga with Monitoring

Continue Farxiga 10 mg daily but monitor closely for volume depletion and hypoglycemia risk. 6 SGLT2 inhibitors may increase hypoglycemia risk when combined with insulin, so a lower insulin dose may ultimately be required. 6 Monitor renal function as both metformin and dapagliflozin require dose adjustment if kidney function declines. 2

Critical Monitoring Requirements

• Check fasting blood glucose daily during insulin titration 2, 3
• Reassess HbA1c after 3 months to determine if additional intensification is needed 1, 2
• Monitor for hypoglycemia, especially with the combination of insulin, SGLT2 inhibitor, and GLP-1 receptor agonist 7, 6
• Assess renal function periodically as both metformin and dapagliflozin require adjustment with declining kidney function 2
• Monitor for signs of volume depletion given the SGLT2 inhibitor use 6

When to Add Prandial Insulin

If HbA1c remains >7% after 3-6 months despite optimized basal insulin and GLP-1 receptor agonist, add prandial insulin. 1, 2 Start with 4 units of rapid-acting insulin before the largest meal or 10% of the basal dose. 2, 3 Clinical signals that indicate the need for prandial insulin include:

• Basal insulin dose exceeding 0.5 units/kg/day 2, 3
• Fasting glucose at target but HbA1c remains elevated 2
• Bedtime-to-morning glucose differential ≥50 mg/dL 2

Address Potential Non-Compliance

While the patient reports compliance, an HbA1c increase from 9.6% to 10.2% suggests either true non-compliance or inadequate therapy. 2 Verify:

• Actual medication-taking behavior through pharmacy refill records
• Proper insulin injection technique and site rotation 3
• Understanding of when and how to take medications
• Barriers to adherence (cost, side effects, complexity)

Important Caveats

Do not delay treatment intensification. 1, 2 Waiting beyond 3 months at HbA1c above target increases complication risk. 2 Medication adjustments should be made promptly to achieve clinically significant improvements. 2

Do not discontinue metformin when intensifying insulin therapy unless contraindicated, as this leads to higher insulin requirements and more weight gain. 4, 3

Watch for overbasalization. 2, 3 If basal insulin exceeds 0.5-1.0 units/kg/day without achieving glycemic targets, adding prandial insulin or intensifying the GLP-1 receptor agonist becomes more appropriate than continuing to escalate basal insulin alone. 2, 3