What is the next step in managing a patient with an A1c of 9 on Januvia (Sitagliptin) 100mg, Jardiance (Empagliflozin) 25mg, Metformin 1000mg twice a day, and Glipizide?

Insulin Therapy is Needed for A1c of 9 on Multiple Medications

For a patient with an A1c of 9% despite being on maximum doses of Januvia (sitagliptin) 100mg, Jardiance (empagliflozin) 25mg, metformin 1000mg twice daily, and glipizide, insulin therapy should be initiated. 1

Rationale for Insulin Therapy

The patient is currently on:

• Maximum dose of metformin (2000mg daily)
• Maximum dose of SGLT2 inhibitor (empagliflozin 25mg)
• Maximum dose of DPP-4 inhibitor (sitagliptin 100mg)
• Sulfonylurea (glipizide)

This represents a comprehensive oral regimen that includes medications from four different classes, yet the A1c remains significantly elevated at 9%, which is:

• 2% above the typical target of 7%
• Well above the threshold of ≥1.5% above goal that indicates need for more intensive therapy 1

Treatment Algorithm

1. Initiate insulin therapy:

   • When A1c is ≥1.5% above target despite multiple oral agents, insulin is indicated 1
   • For patients with A1c >9% on multiple medications, insulin therapy is particularly appropriate 1
   • Common practice is to start insulin when blood glucose levels are persistently elevated despite multiple oral agents 1

2. Insulin regimen options:

   • Begin with basal insulin (glargine, degludec, or NPH)
   • Initial dose: 10 units daily or 0.1-0.2 units/kg/day
   • Titrate by 2-4 units every 3-7 days until fasting glucose targets are reached

3. Medication adjustments:

   • Continue metformin as it complements insulin therapy 1
   • Continue empagliflozin (Jardiance) as it has cardiovascular benefits 1
   • Consider discontinuing sitagliptin (Januvia) as its efficacy is limited when adding insulin
   • Consider discontinuing glipizide to reduce hypoglycemia risk when adding insulin

Alternative Considerations

If insulin is strongly refused by the patient, a GLP-1 receptor agonist could be considered:

• GLP-1 RAs have greater glucose-lowering efficacy than DPP-4 inhibitors 1
• Consider replacing sitagliptin with a GLP-1 RA like semaglutide
• GLP-1 RAs have additional benefits of weight loss and cardiovascular risk reduction 1

Important Clinical Considerations

1. Insulin is most effective for significant hyperglycemia:

   • For A1c >9%, insulin has the most robust glucose-lowering effect 1
   • Other agents typically provide only modest additional A1c reduction (0.5-0.8%) 2

2. Watch for hypoglycemia risk:

   • The combination of insulin and sulfonylurea (glipizide) significantly increases hypoglycemia risk
   • Consider discontinuing glipizide when initiating insulin

3. Monitor for insulin dose adjustments:

   • Check fasting glucose daily during initiation
   • Adjust dose every 3-7 days based on glucose patterns
   • Re-evaluate A1c after 3 months of therapy

4. Patient education is crucial:

   • Proper insulin administration technique
   • Hypoglycemia recognition and management
   • Self-monitoring of blood glucose

This approach prioritizes achieving glycemic control to reduce the risk of diabetes complications while managing the patient's complex medication regimen appropriately.