Can Jardiance (empagliflozin) and semaglutide be used together in patients with type 2 diabetes?

Empagliflozin (Jardiance) and Semaglutide Combination Therapy in Type 2 Diabetes

Yes, empagliflozin (Jardiance) and semaglutide can be used together in patients with type 2 diabetes, and this combination is particularly beneficial for patients with cardiovascular disease or high cardiovascular risk. 1

Rationale for Combination Therapy

• SGLT2 inhibitors (like empagliflozin) and GLP-1 receptor agonists (like semaglutide) have complementary mechanisms of action that provide additive benefits for glycemic control and cardiovascular risk reduction 1
• Both medication classes are recommended as part of glucose-lowering regimens for patients with type 2 diabetes, especially those with established cardiovascular disease or high cardiovascular risk 1
• The combination can provide more robust HbA1c reduction than either agent alone, with GLP-1 RAs typically lowering HbA1c by 1.1-1.5% and SGLT2 inhibitors providing additional reductions 1, 2

Cardiovascular Benefits

• Empagliflozin is specifically recommended to reduce cardiovascular events and risk of death in patients with type 2 diabetes and cardiovascular disease 1
• Semaglutide is recommended for cardiovascular event reduction in patients with type 2 diabetes and cardiovascular disease or high cardiovascular risk 1
• Using both agents together provides complementary cardiovascular protection through different mechanisms 1

Renal Benefits

• SGLT2 inhibitors like empagliflozin are recommended to reduce progression of diabetic kidney disease 1
• Both medication classes have shown beneficial effects on indices of chronic kidney disease in cardiovascular outcomes trials 1
• Recent research suggests the combination may have complementary effects on kidney structure, with both agents reducing total kidney volume 3

Heart Failure Considerations

• Empagliflozin significantly reduces the risk of hospitalization for heart failure 1
• GLP-1 RAs like semaglutide have a neutral effect on heart failure risk 1
• For patients with heart failure, the SGLT2 inhibitor component is particularly important 1

Practical Considerations for Combined Use

• When initiating both medications:

  • Start with one agent first, then add the second after 3-4 weeks to better manage potential side effects 1
  • Monitor for hypoglycemia, especially if the patient is also on sulfonylureas or insulin, and consider dose reductions of these agents 1
  • Be aware of the diuretic effect of SGLT2 inhibitors, which may be relevant when combined with other medications 1

• Side effect management:

  • For GLP-1 RAs: Start with the lowest dose and titrate gradually to minimize gastrointestinal side effects like nausea and vomiting 1
  • For SGLT2 inhibitors: Monitor for genital mycotic infections, volume depletion, and rare but serious side effects like diabetic ketoacidosis 1, 4

Important Cautions

• Avoid this combination in patients with type 1 diabetes due to increased risk of diabetic ketoacidosis with SGLT2 inhibitors 5
• Use caution in patients with a history of proliferative retinopathy when prescribing semaglutide 1
• Monitor renal function when initiating empagliflozin, as it may cause an initial modest decrease in eGFR that is typically hemodynamic and reversible 1
• The combination therapy may have additive effects on weight loss and blood pressure reduction, which should be monitored 3, 6

Evidence for Combination Therapy

• Recent studies have examined the combination of semaglutide and empagliflozin, showing complementary effects on glycemic control 3, 6
• A randomized trial found that adding semaglutide to empagliflozin improved glycemic control and reduced plasma aldosterone levels compared to empagliflozin alone 6
• The combination therapy showed greater reductions in total kidney volume (-5%) compared to either agent alone (-3% for each monotherapy) 3

This combination represents a powerful approach to managing type 2 diabetes with complementary mechanisms that address multiple pathophysiological aspects of the disease while providing cardiovascular and renal protection.