Should another medication be added to Synjardy (empagliflozin and metformin) for a patient with rising HbA1C, considering lack of insurance?

Management of Rising HbA1C in an Uninsured Patient on Synjardy

Recommendation

For a patient with rising HbA1C from 6.5% to 6.9% on Synjardy (empagliflozin/metformin) twice daily, a GLP-1 receptor agonist should be added as the next medication, despite insurance constraints.

Assessment of Current Situation

The patient's glycemic control has deteriorated slightly, with HbA1C rising from 6.5% to 6.9% while on Synjardy (combination of empagliflozin and metformin) twice daily. This indicates:

• Current therapy is becoming inadequate
• The rise is modest but concerning as it crosses the diagnostic threshold for diabetes (6.5%)
• Patient lacks insurance coverage, which significantly impacts treatment decisions

Treatment Algorithm Based on Evidence

Step 1: Evaluate current medication optimization

• Ensure Synjardy is being taken at maximum tolerated dose
• Synjardy contains empagliflozin (SGLT2 inhibitor) and metformin, which is the recommended first-line combination 1, 2
• Confirm twice daily dosing is appropriate (studies show equivalent efficacy between once-daily and twice-daily empagliflozin regimens) 3

Step 2: Determine need for additional therapy

• HbA1C rise from 6.5% to 6.9% indicates therapy intensification is needed
• ADA guidelines recommend adding medications when target glycemic goals are not achieved 1
• The modest rise suggests adding one additional agent rather than switching therapy completely

Step 3: Select appropriate add-on therapy

1. GLP-1 receptor agonist (preferred option)

   • Provides significant A1C reduction
   • Offers weight reduction benefits
   • Low hypoglycemia risk
   • Has cardiovascular protective effects
   • Can be weekly dosing (reducing daily medication burden)

2. Sulfonylurea (alternative if cost is prohibitive)

   • Effective A1C lowering
   • Inexpensive (important for uninsured patients)
   • Higher risk of hypoglycemia and weight gain
   • Studies show efficacy when added to empagliflozin/metformin 4

3. DPP-4 inhibitor (alternative option)

   • Moderate A1C lowering
   • Weight neutral
   • Low hypoglycemia risk
   • More expensive than sulfonylureas

Cost Considerations for Uninsured Patient

The lack of insurance coverage is a critical factor in medication selection:

• GLP-1 receptor agonists: Most expensive option but may be available through patient assistance programs
• Sulfonylureas: Most affordable option (generic available for $4-10/month at many pharmacies)
• DPP-4 inhibitors: Moderate to high cost without insurance

Evidence-Based Rationale

The ADA guidelines recommend rapid addition of medications when target glycemic goals are not achieved 1. For patients with A1C <8%, medications with lesser potential to lower glycemia may be considered 1.

Research demonstrates that adding a third agent to metformin and SGLT2 inhibitor therapy can effectively lower HbA1C. A study of triple therapy with metformin, sitagliptin (DPP-4 inhibitor), and empagliflozin showed that 61.7% of patients achieved HbA1C <7.0% at 24 months 5.

Another study showed that adding empagliflozin to metformin and sulfonylurea therapy reduced HbA1C by 0.82% compared to placebo 4, suggesting that the reverse (adding sulfonylurea to empagliflozin/metformin) would also be effective.

Practical Implementation

1. If financially feasible: Add a GLP-1 receptor agonist (weekly formulation preferred for adherence)

   • Connect patient with manufacturer assistance programs
   • Consider lower-cost GLP-1 options if available

2. If cost is prohibitive: Add a sulfonylurea

   • Start with low dose to minimize hypoglycemia risk
   • Choose newer generation sulfonylureas (glimepiride or glipizide) over older agents
   • Educate on hypoglycemia recognition and management

3. Monitor closely:

   • Check HbA1C in 3 months to assess efficacy
   • Watch for side effects, especially hypoglycemia if sulfonylurea is chosen
   • Adjust dosing as needed

Important Considerations and Pitfalls

• Avoid therapeutic inertia: Delaying intensification of therapy can lead to prolonged hyperglycemia and increased risk of complications 2
• Consider medication interactions: Empagliflozin has minimal drug interactions with most commonly used medications 6
• Watch for side effects: Monitor for genital mycotic infections with SGLT2 inhibitors; hypoglycemia risk increases if adding sulfonylurea 1
• Explore cost-saving strategies: Look into patient assistance programs, discount cards, and community resources for medication access

By following this approach, the patient's glycemic control can be improved while balancing efficacy, safety, and cost considerations in the absence of insurance coverage.