Would adding Cardigan be effective instead of Jardiance (empagliflozin) for managing type 2 diabetes and hyperlipidemia?

Canagliflozin ("Cardigan") Cannot Replace Jardiance (Empagliflozin)

While canagliflozin is an SGLT2 inhibitor with proven cardiovascular benefits similar to empagliflozin, it carries a significantly increased risk of lower-limb amputation that makes it a less favorable choice, particularly in patients with peripheral arterial disease or hyperlipidemia who may already have compromised vascular health. 1

Critical Safety Difference: Amputation Risk

• Canagliflozin demonstrated a nearly 2-fold increased risk of lower-limb amputation (6.3 vs. 3.4 participants per 1,000 patient-years; HR 1.97 [95% CI 1.41-2.75]) in the CANVAS trial 1
• Empagliflozin has not been associated with increased amputation risk or bone fractures, unlike canagliflozin 2
• This amputation signal is particularly concerning for patients with hyperlipidemia, as they likely have underlying atherosclerotic disease that increases baseline amputation risk 1

Cardiovascular Efficacy: Both Effective But Different Profiles

Empagliflozin (Jardiance) Benefits:

• 38% reduction in cardiovascular death (HR 0.62 [95% CI 0.49-0.77]) in EMPA-REG OUTCOME 1, 3
• 14% reduction in composite MACE (MI, stroke, CV death) 1
• 36% reduction in heart failure hospitalization 3
• Demonstrated mortality benefit specifically recommended by guidelines 1

Canagliflozin Benefits:

• 14% reduction in composite MACE (HR 0.86 [95% CI 0.75-0.97]) in CANVAS Program 1
• 30% reduction in kidney disease progression 1
• Similar heart failure hospitalization reduction 1

Guideline Recommendations Favor Empagliflozin for Your Scenario

The 2019 ESC Guidelines specifically recommend empagliflozin to reduce risk of death in patients with type 2 diabetes and cardiovascular disease, while canagliflozin receives a more general recommendation without the mortality emphasis 1

• For patients with established CVD or very high CV risk: empagliflozin, canagliflozin, or dapagliflozin are recommended to reduce CV events 1
• However, empagliflozin is uniquely recommended to reduce risk of death in this population 1
• The 2024 ESC Guidelines for peripheral arterial disease note the amputation concern with canagliflozin but state "the use of other SGLT2is seems reasonable in PAD patients" 1

Practical Clinical Algorithm

If considering switching from empagliflozin to canagliflozin:

1. Assess amputation risk factors 1:

   • History of peripheral arterial disease
   • Prior amputation
   • Diabetic neuropathy
   • Diabetic foot ulcers
   • Poor peripheral circulation

2. If ANY amputation risk factors present: DO NOT switch to canagliflozin 1

3. If no amputation risk factors:

   • Canagliflozin may be considered if there are compelling reasons (cost, availability)
   • Monitor closely for foot complications
   • Educate patient about foot care and early warning signs

4. For hyperlipidemia management specifically:

   • Neither SGLT2 inhibitor directly treats hyperlipidemia
   • Continue statin therapy as primary lipid management 1
   • SGLT2 inhibitors provide CV risk reduction beyond lipid effects 1, 4

Why This Matters for Your Patient

• Hyperlipidemia indicates underlying atherosclerotic disease, which increases baseline amputation risk 1
• The mortality benefit of empagliflozin (38% reduction in CV death) is clinically more meaningful than the marginal differences in MACE reduction between the two drugs 1, 3
• Empagliflozin has a cleaner safety profile without the amputation or fracture concerns 2, 5

Common Pitfalls to Avoid

• Do not assume all SGLT2 inhibitors are interchangeable - the amputation signal is specific to canagliflozin 1, 2
• Do not switch based solely on cost without considering the amputation risk in patients with vascular disease 1
• Do not forget that both drugs require monitoring for genital mycotic infections, volume depletion, and euglycemic DKA 1

Bottom line: Unless there are exceptional circumstances (severe drug shortage, documented intolerance to empagliflozin), maintain empagliflozin rather than switching to canagliflozin, especially given the patient's hyperlipidemia suggesting underlying vascular disease. 1, 2