What is the difference between Januvia (sitagliptin) and Jardiance (empagliflozin) for treating type 2 diabetes?

Januvia vs Jardiance for Type 2 Diabetes

Jardiance (empagliflozin) is superior to Januvia (sitagliptin) for treating type 2 diabetes, particularly in patients with established cardiovascular disease, heart failure, or chronic kidney disease, due to its proven cardiovascular and renal benefits. 1

Mechanism of Action Differences

• Januvia (sitagliptin) is a DPP-4 inhibitor that works by increasing incretin levels, which inhibits glucagon release and increases insulin secretion 2
• Jardiance (empagliflozin) is an SGLT2 inhibitor that works by increasing urinary glucose excretion through inhibition of glucose reabsorption in the kidneys 3, 4

Cardiovascular Outcomes

• Jardiance significantly reduces the risk of cardiovascular death by 38% in patients with established cardiovascular disease 5, 6
• Jardiance reduces hospitalization for heart failure by 35% compared to placebo 7, 3
• Januvia (sitagliptin) has a neutral effect on cardiovascular outcomes with no significant reduction in major adverse cardiovascular events 7, 2
• In direct comparison studies, empagliflozin showed a 32% reduction in the modified MACE outcome compared to sitagliptin (HR 0.68; 95% CI, 0.60-0.77) 1

Renal Benefits

• Jardiance provides significant renal protection, reducing the risk of a prespecified renal composite outcome by 50% compared to placebo (HR 0.50; 95% CI 0.32-0.77) 7, 3
• Jardiance can restore tubuloglomerular feedback and reduce intraglomerular pressure, providing nephroprotective effects independent of glycemic control 5
• Sitagliptin has not demonstrated significant renal protective benefits in major clinical trials 2

Heart Failure Considerations

• Jardiance reduces the risk of hospitalization for heart failure by 55% compared to sitagliptin (HR 0.45; 95% CI, 0.36-0.56) 1
• Unlike some other DPP-4 inhibitors (like saxagliptin), sitagliptin does not increase the risk of heart failure hospitalization 7, 2
• Jardiance is specifically recommended for patients with heart failure due to its proven benefits in reducing heart failure hospitalizations 7

Glycemic Control

• Both medications effectively lower blood glucose levels, with similar A1C reductions (0.3-0.8%) 4, 8, 9
• Jardiance provides additional benefits beyond glycemic control, including modest weight reduction (2.1-2.5 kg) and blood pressure reduction (2.9-5.2 mmHg) 8
• Januvia is weight-neutral and does not significantly affect blood pressure 2

Safety Considerations

• Jardiance is associated with increased risk of genital mycotic infections (approximately 6% of patients) 5, 4
• Jardiance requires monitoring for volume depletion, especially in elderly patients or those on diuretics 3
• Jardiance should not be initiated if eGFR is below 45 mL/min/1.73 m² 3
• Both medications have a low risk of hypoglycemia when used as monotherapy 4, 9

Patient Selection Algorithm

For patients with type 2 diabetes, consider:

1. Patients with established cardiovascular disease or high CV risk:

   • Prefer Jardiance due to proven cardiovascular mortality benefit 7, 5, 1

2. Patients with heart failure or at risk for heart failure:

   • Strongly prefer Jardiance due to significant reduction in heart failure hospitalizations 7, 1

3. Patients with chronic kidney disease:

   • Prefer Jardiance for its renal protective effects 7, 3, 1

4. Patients with normal renal function requiring glycemic control:

   • Either medication is appropriate, but Jardiance offers additional benefits of weight loss and blood pressure reduction 8

5. Patients with severe renal impairment (eGFR < 45 mL/min/1.73 m²):

   • Consider Januvia with appropriate dose adjustment rather than Jardiance 3, 2

Clinical Implications

• The absolute benefits of Jardiance vs. sitagliptin are larger in patients with established cardiovascular disease, heart failure, or chronic kidney disease 1
• For older adults with type 2 diabetes, Jardiance is associated with better cardiovascular outcomes compared to sitagliptin across all patient subgroups 1
• When considering medication choice, evaluate the patient's cardiovascular risk, renal function, and presence of heart failure to guide decision-making 7, 5