What is the best next step for a patient with T2DM, hypertension, and history of stroke, on metformin and sitagliptin, with hyperglycemia and mildly impaired renal function?

Initiate Canagliflozin 100 mg Orally Once Daily for T2DM Patient with History of Stroke

For this 64-year-old male with type 2 diabetes, hypertension, history of stroke, and inadequate glycemic control (A1c 7.8%) on metformin and sitagliptin, initiating canagliflozin 100 mg orally once daily is the most appropriate recommendation. 1

Rationale for Adding SGLT2 Inhibitor

The patient has several factors that make an SGLT2 inhibitor the optimal choice:

1. Cardiovascular Disease History: The patient had a stroke 8 months ago, placing him in a high cardiovascular risk category. SGLT2 inhibitors have proven cardiovascular benefits 1

2. Inadequate Glycemic Control: Current A1c of 7.8% indicates that the patient's diabetes is not adequately controlled on current therapy (metformin + sitagliptin)

3. Preserved Renal Function: The patient has an eGFR of 78 mL/min/1.73 m², which is appropriate for SGLT2 inhibitor therapy 1, 2

Why Canagliflozin Specifically?

Canagliflozin is particularly appropriate for this patient because:

• The CREDENCE trial demonstrated that canagliflozin reduced the relative risk of renal outcomes by 30% compared to placebo 1
• Canagliflozin has been shown to reduce the risk of hemorrhagic stroke 3
• The ESC guidelines specifically recommend canagliflozin for patients with T2DM and eGFR 30 to <90 mL/min/1.73 m² 1
• Canagliflozin can be safely used at 100 mg daily with the patient's current eGFR of 78 mL/min/1.73 m² 4, 5

Why Not Other Options?

Why Not Exenatide?

• While GLP-1 RAs are recommended for patients who don't meet glycemic targets with metformin and SGLT2i, they are generally considered after SGLT2i in patients with cardiovascular disease 1
• Exenatide specifically requires eGFR >30 mL/min, but other GLP-1 RAs would be more appropriate if this class were selected 1

Why Not Oral Semaglutide?

• While semaglutide has cardiovascular benefits, SGLT2 inhibitors are preferred first-line add-on therapy for patients with established cardiovascular disease 1, 2
• The proposed dose of 3 mg is only the starting dose for oral semaglutide and would need to be titrated up for efficacy

Why Not Continue Current Regimen?

• The patient's A1c of 7.8% indicates inadequate glycemic control on current therapy
• The patient's history of stroke warrants addition of an agent with proven cardiovascular benefits

Monitoring and Follow-up

When initiating canagliflozin:

• Monitor renal function (eGFR) every 3-6 months 2
• Watch for genital mycotic infections, particularly in males (occurs in approximately 4% of males) 4
• Be aware that risk of hypoglycemia is low when added to metformin and sitagliptin but increases if sulfonylureas or insulin are added 4
• Monitor for volume depletion, especially given the patient's history of hypertension 4

Potential Benefits Beyond Glycemic Control

Adding canagliflozin offers several benefits beyond glucose lowering:

• Cardiovascular protection, particularly important given the patient's stroke history 1
• Potential renoprotection, helping preserve kidney function 1, 3
• Blood pressure reduction, beneficial for the patient's hypertension 6
• Weight reduction, which may further improve cardiovascular risk profile 6, 7

Conclusion

Based on the most recent guidelines and evidence, initiating canagliflozin 100 mg daily is the optimal next step for this patient with T2DM, hypertension, and history of stroke who has inadequate glycemic control on metformin and sitagliptin.