Can I start the patient on Invokana (canagliflozin) while they are on metformin and have declined sodium‑glucose cotransporter‑2 (SGL‑2) inhibitor therapy?

Understanding the Patient's Concern About SGLT-2 Inhibitors

You cannot start Invokana (canagliflozin) if the patient has declined SGLT-2 inhibitor therapy, because Invokana IS an SGLT-2 inhibitor. 1

It appears there may be confusion about medication classes. Let me clarify the situation and provide guidance on what to do when a patient declines SGLT-2 inhibitor therapy.

Clarifying Medication Classes

• Invokana (canagliflozin) is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, not an alternative to this drug class 1, 2
• If the patient has declined SGLT-2 inhibitor therapy, they are specifically declining medications like Invokana, along with empagliflozin and dapagliflozin 3

Alternative Therapy When SGLT-2 Inhibitors Are Declined

When a patient on metformin declines SGLT-2 inhibitor therapy, add a GLP-1 receptor agonist (such as semaglutide, dulaglutide, or liraglutide) as the preferred second-line agent for cardiovascular and renal protection. 3, 4

Why GLP-1 Receptor Agonists Are the Next Best Choice

• The 2024 American Diabetes Association guidelines recommend GLP-1 receptor agonists as the alternative cardioprotective agent when SGLT-2 inhibitors cannot be used 3
• GLP-1 receptor agonists provide proven cardiovascular benefit, reducing major adverse cardiovascular events by similar magnitudes to SGLT-2 inhibitors in patients with established atherosclerotic disease 4, 5
• These agents promote weight loss, have minimal hypoglycemia risk when used without sulfonylureas or insulin, and require no dose adjustment for renal function 4, 5

Specific GLP-1 Receptor Agonist Options

• Dulaglutide: Start at 0.75 mg weekly, increase to 1.5 mg weekly; no renal dose adjustment needed at any eGFR level 4, 5
• Liraglutide: Start at 0.6 mg daily, titrate to 1.2-1.8 mg daily; no renal dose adjustment needed 4, 5
• Semaglutide: Injectable 0.5-1 mg weekly or oral 3-14 mg daily; no renal dose adjustment needed 5

Addressing Patient Concerns About SGLT-2 Inhibitors

Before accepting the patient's declination, explore the specific reasons for their reluctance, as many concerns can be addressed through education:

Common Patient Concerns and Solutions

• Genital mycotic infections: Occur in 10-15% of patients but can be minimized with proper genital hygiene education and are easily treatable 3
• Urinary tract infections: Actual incidence is only modestly increased and should not deter use in most patients 3
• Cost concerns: Discuss insurance coverage options and patient assistance programs, as the cardiovascular and renal benefits often justify the expense 3
• Fear of ketoacidosis: Euglycemic diabetic ketoacidosis is rare (occurring in <0.1% of patients) and can be prevented through proper patient education about sick-day management 3

Cardiovascular and Renal Benefits the Patient Would Miss

• SGLT-2 inhibitors reduce cardiovascular death or heart failure hospitalization by 26-29% 5
• They slow kidney disease progression by 39-44% 5
• They reduce all-cause mortality by 31% in patients with cardiovascular disease or risk factors 5
• These benefits occur independently of glucose lowering and persist even when eGFR falls below 45 mL/min/1.73 m² 3, 5

Clinical Decision Algorithm

1. Confirm the patient understands that Invokana IS an SGLT-2 inhibitor and clarify what they are actually declining 1

2. If declining all SGLT-2 inhibitors after informed discussion:

   • Add a GLP-1 receptor agonist (dulaglutide, liraglutide, or semaglutide) to metformin 3, 4
   • Choose based on patient preference for weekly vs. daily dosing and injection vs. oral route 5

3. If the patient has cardiovascular disease, heart failure, or chronic kidney disease:

   • Strongly reconsider the SGLT-2 inhibitor discussion, as these patients derive the greatest benefit 3
   • Document the detailed discussion and patient's informed refusal if they still decline 3

4. If both SGLT-2 inhibitors and GLP-1 receptor agonists are declined or not tolerated:

   • Consider DPP-4 inhibitors (linagliptin requires no renal dose adjustment) as a third-line option, though these lack cardiovascular outcome benefits 4, 5

Critical Safety Note

• Do not continue or add sulfonylureas when initiating cardioprotective agents, as they increase hypoglycemia risk without providing cardiovascular or renal protection 3, 5
• The 2024 ADA guidelines recommend reassessing and discontinuing sulfonylureas when adding SGLT-2 inhibitors or GLP-1 receptor agonists 5