What is the next treatment option for a patient with poorly controlled diabetes, indicated by an elevated Hemoglobin A1c (HbA1c) level, while currently taking 100 mg of Invokana (Canagliflozin)?

Management of Poorly Controlled Diabetes with HbA1c of 9.7% on Invokana 100 mg

For a patient with an HbA1c of 9.7% while on Invokana (canagliflozin) 100 mg, the next step should be to increase the Invokana dose to 200-300 mg daily and consider adding a GLP-1 receptor agonist with proven cardiovascular benefit.

Assessment of Current Therapy

• The patient's HbA1c of 9.7% indicates poor glycemic control, significantly above the standard target of <7% recommended by the American Diabetes Association 1
• Current therapy with Invokana 100 mg is suboptimal, as the patient has not achieved target glycemic control
• Invokana (canagliflozin) is an SGLT2 inhibitor that can be titrated up to 300 mg daily for improved glycemic control 2

Treatment Algorithm

Step 1: Optimize Current Therapy

• Increase Invokana from 100 mg to 300 mg daily
  • This higher dose provides greater HbA1c reduction compared to the 100 mg dose (1.03% vs 0.77% reduction) 3
  • FDA labeling supports dose escalation for improved glycemic control 2

Step 2: Add a Second Agent Based on Patient Characteristics

• Add a GLP-1 receptor agonist with proven cardiovascular benefit
  • The American Diabetes Association recommends adding a GLP-1 receptor agonist when A1c remains ≥1.5% above target 1
  • GLP-1 receptor agonists have shown superior HbA1c reduction compared to insulin in patients with high baseline HbA1c values 4
  • Studies show that GLP-1 receptor agonists can reduce HbA1c by approximately 2.5% from a baseline of 10% 4

Alternative Approach if GLP-1 RA is Not Suitable:

• Consider basal insulin therapy
  • Particularly appropriate if patient shows symptoms of significant hyperglycemia (polyuria, polydipsia, weight loss)
  • The American Diabetes Association suggests early insulin introduction if there is evidence of ongoing catabolism or very high blood glucose levels 1

Rationale for Recommendation

1. Dose Optimization: Canagliflozin 300 mg provides greater HbA1c reduction than 100 mg dose (1.03% vs 0.77%) 3

2. Complementary Mechanism: GLP-1 receptor agonists work through different mechanisms than SGLT2 inhibitors, providing additive benefits:

   • SGLT2 inhibitors reduce glucose reabsorption in kidneys
   • GLP-1 RAs improve insulin secretion, reduce glucagon, and slow gastric emptying

3. Evidence for Combination: Studies show that combination therapy with SGLT2 inhibitors and GLP-1 RAs can achieve HbA1c reductions of approximately 2.2% from a baseline of 10% 4

4. Weight Benefits: Both medication classes promote weight loss, unlike insulin which typically causes weight gain 4, 5

5. Cardiovascular Protection: Both medication classes offer cardiovascular benefits in patients with or at high risk for cardiovascular disease 1

Monitoring and Follow-up

• Schedule follow-up HbA1c in 3 months to assess response to therapy 1
• Monitor for side effects of increased Invokana dose and addition of GLP-1 RA:
  • Genital mycotic infections (more common with SGLT2 inhibitors) 6
  • Gastrointestinal side effects (common with GLP-1 RAs)
  • Osmotic diuresis and volume depletion 6
  • Hypoglycemia (risk is low with this combination but increases if sulfonylureas are added) 3

Caveats and Considerations

• If the patient has renal impairment (eGFR <60 mL/min/1.73 m²), dose adjustment of Invokana may be needed 2
• Consider insulin therapy if patient shows signs of significant insulin deficiency or catabolic state
• Ensure that lifestyle modifications (medical nutrition therapy, physical activity, weight management) are optimized alongside pharmacologic therapy 1
• Address cardiovascular risk factors including blood pressure and lipid management as part of comprehensive diabetes care 1