What is the preferred treatment between Jardiance (Empagliflozin) and Actos (Pioglitazone) for patients with type 2 diabetes mellitus?

Jardiance (Empagliflozin) is Superior to Actos (Pioglitazone) for Type 2 Diabetes Treatment

For patients with type 2 diabetes mellitus, Jardiance (empagliflozin) is recommended over Actos (pioglitazone) due to its superior cardiovascular benefits, mortality reduction, and better side effect profile. 1

Cardiovascular Benefits

• Empagliflozin significantly reduces cardiovascular death by 38% in patients with established cardiovascular disease, making it a preferred choice for diabetic patients with or at high risk for cardiovascular complications 1
• Empagliflozin reduces hospitalization for heart failure by 35%, providing substantial benefit for patients with type 2 diabetes who are at risk for heart failure 1
• Pioglitazone is specifically contraindicated in patients with heart failure (Class III recommendation), limiting its use in a significant portion of diabetic patients 1
• The European Society of Cardiology specifically recommends empagliflozin for patients with type 2 diabetes and cardiovascular disease to reduce the risk of death 1

Mortality Benefits

• Empagliflozin has demonstrated a clear mortality benefit in clinical trials, with overall mortality reduction compared to placebo (5.7% versus 8.3%) 2
• The EMPA-REG OUTCOME trial showed that empagliflozin treatment reduced the composite outcome of MI, stroke, and cardiovascular death by 14% compared to placebo 1
• While pioglitazone has shown some cardiovascular benefits in the PROactive study, it has not demonstrated the same magnitude of mortality benefit as empagliflozin 3, 4

Renal Benefits

• Empagliflozin provides renal protection benefits, which is particularly important as diabetic kidney disease is a common complication 1
• SGLT2 inhibitors like empagliflozin reduce the risk of renal composite outcomes, including sustained decline in eGFR, end-stage kidney disease, or death from renal causes 1
• Empagliflozin can restore tubuloglomerular feedback and reduce intraglomerular pressure, providing nephroprotective effects independent of glycemic control 1

Weight Management

• Empagliflozin promotes weight loss, which is beneficial for most type 2 diabetes patients who are often overweight or obese 5
• In direct comparison studies, switching from pioglitazone to dapagliflozin (another SGLT2 inhibitor similar to empagliflozin) resulted in significant weight loss, while patients continuing pioglitazone experienced weight gain 5
• Pioglitazone is associated with weight gain and fluid retention, which can exacerbate heart failure and edema 4

Side Effect Considerations

• Pioglitazone carries risks of fluid retention, weight gain, and potential increased risk of bladder cancer and bone fractures 3
• Empagliflozin's main side effects include genital mycotic infections, volume depletion, and rare cases of diabetic ketoacidosis 2
• The risk of lower limb amputation seen with canagliflozin (another SGLT2 inhibitor) has not been specifically associated with empagliflozin 1

Special Populations

• For patients with established cardiovascular disease or multiple cardiovascular risk factors, empagliflozin is clearly preferred due to its proven cardiovascular benefits 1
• In patients with diabetic kidney disease, empagliflozin offers additional benefits beyond glycemic control 1
• For patients with nonalcoholic fatty liver disease (NAFLD), both medications improve liver steatosis, but empagliflozin has shown superior effects in reducing controlled attenuation parameter compared to pioglitazone 6

Clinical Algorithm for Selection

1. For patients with established cardiovascular disease or high cardiovascular risk: Choose empagliflozin 1
2. For patients with heart failure or at risk for heart failure: Choose empagliflozin (pioglitazone is contraindicated) 1
3. For patients with chronic kidney disease: Choose empagliflozin 1
4. For patients where weight management is a priority: Choose empagliflozin 5
5. For patients with NAFLD: Empagliflozin provides better improvement in liver steatosis 6

Monitoring Recommendations

• When initiating empagliflozin, monitor for genital mycotic infections (occurs in approximately 6% of patients) 7
• Assess volume status, especially in patients on multiple medications that can affect fluid balance 7
• Be vigilant for euglycemic diabetic ketoacidosis, particularly during periods of acute illness or reduced food intake 7
• Regular monitoring of renal function is recommended when using empagliflozin 7