Can we add Farxiga (Dapagliflozin) 5mg daily to a noncompliant patient with HbA1c of 14% on Glipizide (GlipiZIDE)-Metformin (metFORMIN) HCl 5-500 MG Tablet?

Managing Poorly Controlled Type 2 Diabetes with Dapagliflozin Add-On Therapy

Adding Farxiga (dapagliflozin) 5mg daily is appropriate and recommended for this patient with an HbA1c of 14% who is currently on glipizide-metformin combination therapy. 1, 2

Rationale for Adding Dapagliflozin

The patient's extremely elevated HbA1c of 14% indicates severe hyperglycemia requiring intensification of therapy. According to the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) consensus report, when HbA1c levels exceed 9%, additional glucose-lowering medication should be considered 1.

For patients with such poor glycemic control:

• Early introduction of additional agents is well-established, particularly when HbA1c levels are very high (>11%) 1
• SGLT2 inhibitors like dapagliflozin have demonstrated efficacy in patients with HbA1c levels exceeding 9% 1
• Dapagliflozin can reduce HbA1c by 0.6-1.0% when added to metformin 2

Benefits of Adding Dapagliflozin in This Case

1. Complementary Mechanism of Action: Dapagliflozin works independently of insulin by increasing urinary glucose excretion, which complements the existing sulfonylurea (glipizide) and metformin therapy 3

2. Efficacy in Poorly Controlled Diabetes: In clinical trials, dapagliflozin added to metformin plus sulfonylurea provided significant HbA1c reductions (placebo-subtracted change of -0.69%) 4

3. Weight Reduction Benefits: The patient's poor control likely involves insulin resistance, and dapagliflozin offers weight reduction benefits (typically 1.1-2.1 kg) which can help improve insulin sensitivity 4, 5

4. Low Risk of Hypoglycemia: Despite adding a third agent, the risk of severe hypoglycemia with dapagliflozin is lower than intensifying insulin secretagogue therapy 6

5. Cardiovascular Benefits: SGLT2 inhibitors provide cardiovascular and renal benefits, which are important considerations for patients with long-standing, poorly controlled diabetes 2

Addressing Medication Nonadherence

The patient's nonadherence must be addressed concurrently with medication adjustment:

• Simplify Regimen: Adding once-daily dapagliflozin rather than increasing insulin secretagogue dose may improve adherence 2
• Education: Comprehensive diabetes self-management education focusing on the importance of medication adherence is essential 2
• Follow-up: Schedule close follow-up within 3-6 months to assess adherence and response 1

Monitoring and Safety Considerations

When initiating dapagliflozin:

• Monitor for Genital Infections: Patients on dapagliflozin have increased risk of genital infections (5.5% vs 0% with placebo) 4
• Urinary Tract Infections: Monitor for UTIs, though the increased risk is modest (6.4% in both dapagliflozin and placebo groups) 4
• Hypoglycemia Risk: While the risk is lower than with increasing sulfonylurea doses, combination therapy with sulfonylureas does increase hypoglycemia risk (12.8% vs 3.7% with placebo) 4
• Blood Pressure: Monitor for potential blood pressure reduction (typically 2.3-5.3 mmHg systolic) 3, 4

Alternative Approaches

If dapagliflozin is contraindicated or not tolerated:

1. GLP-1 Receptor Agonists: Consider as an alternative add-on therapy, especially if weight loss is a priority 2
2. Insulin Therapy: For HbA1c >11%, basal insulin could be considered, especially with symptoms of hyperglycemia 1
3. DPP-4 Inhibitors: Could be considered if weight neutrality is desired, though efficacy is generally less than SGLT2 inhibitors 2

Conclusion

Adding dapagliflozin 5mg daily to the current glipizide-metformin regimen is appropriate for this patient with severely elevated HbA1c. This approach provides complementary glucose-lowering effects through an insulin-independent mechanism, offers weight reduction benefits, and has a favorable risk profile compared to increasing doses of insulin secretagogues.