Is it acceptable to start a patient with a high Hemoglobin A1c (HbA1c) level, who is non-compliant with their diabetic medication and refuses insulin, on a combination of Galvumet (vildagliptin and metformin), Jardiance (empagliflozin) 25 mg once daily, and gliclazide 10 mg twice daily?

Management of Severe Hyperglycemia in a Non-Compliant Patient

For a patient with HbA1c of 98 mmol/mol (approximately 11%) who has been non-compliant with diabetic medication for five years and refuses insulin, the proposed combination of Galvumet (vildagliptin/metformin), Jardiance (empagliflozin) 25 mg daily, and gliclazide 10 mg twice daily is an appropriate and evidence-based treatment approach.

Assessment of Proposed Regimen

Metformin-Based Therapy

• Metformin (contained in Galvumet) remains the preferred first-line agent for type 2 diabetes according to current guidelines 1
• Continuing metformin is recommended when used in combination with other agents due to its efficacy, safety profile, and potential cardiovascular benefits 1

Multiple Drug Approach for High HbA1c

• For patients with HbA1c ≥9% (75 mmol/mol), initiating dual or triple therapy is recommended 1, 2
• The ADA Standards of Care specifically recommend considering dual therapy in patients with newly diagnosed type 2 diabetes who have A1C ≥9% (75 mmol/mol) 1
• For very high HbA1c levels (>11%), early introduction of multiple agents is appropriate to achieve better glycemic control 2

Components of the Proposed Regimen

1. Galvumet (vildagliptin/metformin):

   • Combination of DPP-4 inhibitor with metformin provides complementary mechanisms of action
   • Studies show superior efficacy of vildagliptin plus metformin combination compared to individual monotherapies, with HbA1c reductions of up to 1.8% 3
   • Well-tolerated with low risk of hypoglycemia

2. Empagliflozin (Jardiance) 25 mg daily:

   • SGLT2 inhibitor with proven cardiovascular benefits 4
   • Can reduce HbA1c by 0.6-1.0% when added to metformin 2
   • Provides additional benefits of weight reduction and blood pressure lowering 5
   • FDA-approved dosing of 10-25 mg once daily 4

3. Gliclazide 10 mg twice daily:

   • Sulfonylurea that stimulates insulin secretion
   • Provides rapid glucose-lowering effect
   • Combination of empagliflozin with metformin and sulfonylurea has been shown to significantly reduce HbA1c compared to placebo 4

Benefits of This Approach

1. Addresses Patient Preferences: Respects the patient's wish to avoid insulin while still providing effective therapy

2. Targets Multiple Pathways: Combines three different mechanisms of action:

   • Insulin sensitization (metformin)
   • Enhanced incretin effect (vildagliptin)
   • Increased urinary glucose excretion (empagliflozin)
   • Increased insulin secretion (gliclazide)

3. Evidence-Based Efficacy: Studies show that combination therapy can achieve significant HbA1c reductions even in patients with very high baseline levels 6, 5

   • Research indicates that non-insulin combinations can achieve HbA1c reductions of 2-3% in patients with baseline HbA1c >10% 6

Important Considerations and Monitoring

1. Close Follow-up Required:

   • Schedule follow-up within 3-6 months to assess adherence and response 2
   • Check HbA1c quarterly until glycemic targets are achieved 2

2. Potential Side Effects to Monitor:

   • Genital and urinary tract infections with empagliflozin 5
   • Risk of hypoglycemia with sulfonylurea component
   • Gastrointestinal side effects from metformin
   • Volume depletion and hypotension with empagliflozin 4

3. Renal Function Assessment:

   • Assess renal function prior to initiation and periodically thereafter
   • Empagliflozin should not be initiated if eGFR is less than 45 mL/min/1.73 m² 4

4. Addressing Non-Compliance:

   • Comprehensive diabetes self-management education is essential 2
   • Focus on patient education regarding medication adherence, blood glucose monitoring, and lifestyle modifications

Alternative Considerations

If this regimen fails to achieve adequate glycemic control after 3 months, consider:

• Increasing doses if not at maximum
• Adding or substituting a GLP-1 receptor agonist
• Revisiting the discussion about insulin therapy

Conclusion

The proposed combination of Galvumet, Jardiance 25 mg daily, and gliclazide 10 mg twice daily is an appropriate treatment strategy for this non-compliant patient with severe hyperglycemia who refuses insulin. This multi-drug approach targets different pathophysiological mechanisms of type 2 diabetes and is supported by current guidelines and evidence for patients with high HbA1c levels.