Can Jardiance (empagliflozin) be used in patients with type 2 diabetes and Peripheral Artery Disease (PAD)?

Empagliflozin (Jardiance) Use in Type 2 Diabetes with Peripheral Artery Disease

Empagliflozin (Jardiance) is strongly recommended for patients with type 2 diabetes and peripheral artery disease (PAD) as it reduces cardiovascular events and may provide limb benefits. 1

Benefits of Empagliflozin in PAD

Empagliflozin offers significant advantages for patients with type 2 diabetes and PAD:

• Cardiovascular benefits: In the EMPA-REG OUTCOME trial, which included 20.8% of patients with PAD at baseline, empagliflozin demonstrated:

  • 14% reduction in major adverse cardiovascular events (MACE) 1, 2
  • 38% reduction in cardiovascular death 1, 2
  • 35% reduction in hospitalization for heart failure 2
  • 32% reduction in all-cause mortality 2

• Limb-specific outcomes: In patients with PAD specifically, empagliflozin showed:

  • 43% reduction in cardiovascular death (HR 0.57; 95% CI 0.37-0.88) 1
  • 38% reduction in all-cause mortality (HR 0.62; 95% CI 0.44-0.88) 1
  • Non-significant trend toward reduced limb amputations (5.5% with empagliflozin vs. 6.3% with placebo) 1

• Additional benefits:

  • Moderate glucose-lowering effect (HbA1c reduction of approximately 0.5-1.0%) 1, 3
  • Blood pressure reduction 4
  • Weight reduction 5

Safety Considerations in PAD

• Amputation risk: Unlike canagliflozin (which initially showed increased amputation risk in the CANVAS trial), empagliflozin has not been associated with increased risk of lower limb amputations 1, 5

  • A subgroup analysis of patients with PAD in EMPA-REG OUTCOME actually showed superior limb survival with empagliflozin versus placebo 1
  • The FDA removed the black box warning for amputation risk from canagliflozin in 2020 after subsequent studies did not confirm this risk 1

• Common side effects:

  • Genital mycotic infections 5, 6
  • Potential volume depletion (rare) 4
  • Low risk of hypoglycemia when used without insulin or sulfonylureas 3, 5

Treatment Algorithm for Type 2 Diabetes with PAD

1. First-line therapy: Metformin remains first-line therapy for most patients with type 2 diabetes 3

2. Second-line therapy: For patients with type 2 diabetes and PAD:

   • Strongly recommended: SGLT2 inhibitor with proven cardiovascular benefit (empagliflozin) 1
   • Alternative if SGLT2 inhibitor contraindicated: GLP-1 receptor agonist with proven cardiovascular benefit (liraglutide, semaglutide) 1

3. Glycemic targets:

   • Aim for HbA1c <53 mmol/mol (7%) to reduce microvascular complications 1
   • Consider higher targets (up to 8.5%) for patients with limited life expectancy or when treatment risks outweigh benefits 1
   • Avoid hypoglycemia 1

Clinical Pearls and Pitfalls

• Screening for asymptomatic PAD is recommended in people with diabetes who are:

  • Age ≥65 years
  • Diabetes duration ≥10 years
  • Have microvascular disease or foot complications
  • Have any end-organ damage from diabetes 1

• Diagnosis of PAD may be challenging in diabetes patients as classical symptoms of claudication are often absent due to peripheral neuropathy 1

• Coordinated care among clinicians is essential for managing diabetes in PAD patients, addressing diet, exercise, weight management, glycemic control, cardiovascular risk factors, and foot care 1

• Monitor for side effects: Educate patients about symptoms of genital mycotic infections and volume depletion 3

• Renal function: Empagliflozin has decreased efficacy when eGFR <45 mL/min/1.73m² and is not recommended for eGFR <30 mL/min/1.73m² 3

In conclusion, empagliflozin is an excellent choice for patients with type 2 diabetes and PAD due to its proven cardiovascular benefits, potential limb benefits, and favorable safety profile compared to other agents in its class.