What would you recommend for a patient on insulin and metformin (biguanide) with continually elevated glucose levels on Onglyza (saxagliptin), considering SGLT2 (sodium-glucose cotransporter 2) medications are not feasible due to cost?

Management of Inadequate Glycemic Control in a Patient on Insulin, Metformin, and Saxagliptin

For a patient on insulin and metformin with continually elevated glucose levels on saxagliptin (Onglyza), a sulfonylurea is the recommended next step when SGLT2 inhibitors are too expensive.

Treatment Algorithm for Patients with Inadequate Glycemic Control

Current Medication Assessment

• Patient is currently on:
  • Insulin (basal)
  • Metformin (biguanide)
  • Saxagliptin (DPP-4 inhibitor)
• Glycemic control remains inadequate
• SGLT2 inhibitors are not feasible due to cost constraints

Recommended Medication Addition/Substitution

1. Add a sulfonylurea

   • Sulfonylureas are low-cost alternatives to SGLT2 inhibitors 1
   • They provide potent glucose-lowering effects
   • Examples include glipizide, glyburide, and glimepiride

2. Consider discontinuing saxagliptin

   • DPP-4 inhibitors (like saxagliptin) have been shown to be less effective and potentially more expensive compared to sulfonylureas when added to metformin 1
   • Adding a sulfonylurea while continuing saxagliptin may increase the risk of hypoglycemia without substantial additional benefit

3. Adjust insulin dosing

   • When adding a sulfonylurea, carefully titrate insulin to avoid hypoglycemia
   • Monitor blood glucose more frequently during the transition period

Rationale for Recommendation

The KDIGO 2020 clinical practice guideline recommends that when cost is a significant factor in medication selection, sulfonylureas are appropriate alternatives for patients who cannot afford SGLT2 inhibitors 1. While SGLT2 inhibitors would be preferred due to their cardiovascular and renal benefits, their high cost is a legitimate barrier to access 2.

The American College of Physicians (2024) acknowledges that "there are currently no generic SGLT2 inhibitors" and recommends that "clinicians and patients should discuss the cost of an add-on SGLT2 inhibitor or GLP-1 agonist when selecting a medication" 1.

Important Monitoring Considerations

• Hypoglycemia risk: Closely monitor for hypoglycemia when adding a sulfonylurea to insulin therapy
• Renal function: Assess kidney function before initiating sulfonylureas and periodically thereafter
• Weight changes: Be aware that sulfonylureas may cause weight gain, unlike SGLT2 inhibitors which promote weight loss

Potential Pitfalls and Caveats

• Hypoglycemia risk: The combination of insulin and sulfonylureas significantly increases hypoglycemia risk. Start with a low dose of sulfonylurea and adjust carefully.
• Weight gain: Unlike SGLT2 inhibitors which promote weight loss, sulfonylureas may cause weight gain.
• Cardiovascular benefits: Sulfonylureas do not offer the cardiovascular and renal protective effects seen with SGLT2 inhibitors.
• Duration of effect: Sulfonylureas may have diminishing effects over time (secondary failure).

Alternative Options if Sulfonylureas Are Contraindicated

If sulfonylureas are contraindicated or not tolerated:

1. Thiazolidinediones (TZDs)

   • Consider pioglitazone as an alternative low-cost option
   • Be cautious in patients with heart failure risk or osteoporosis

2. Optimize insulin regimen

   • Consider splitting insulin into basal-bolus regimen
   • More aggressive titration of existing insulin

3. Patient assistance programs

   • Explore manufacturer assistance programs for SGLT2 inhibitors
   • Check insurance formularies for preferred SGLT2 inhibitors with lower copays

The combination of insulin, metformin, and a sulfonylurea represents a cost-effective approach to managing diabetes when more expensive newer agents are not accessible due to cost constraints 1.