Can Jardiance (Empagliflozin) and Ozempic (Semaglutide) be used together in patients with type 2 diabetes?

Combination of Jardiance (Empagliflozin) and Ozempic (Semaglutide) in Type 2 Diabetes

Yes, Jardiance (empagliflozin) and Ozempic (semaglutide) can be used together in patients with type 2 diabetes, particularly in those with established cardiovascular disease or at high cardiovascular risk, as this combination offers complementary mechanisms of action and potential additive benefits for cardiovascular and metabolic outcomes. 1, 2

Evidence Supporting Combination Therapy

The American College of Cardiology expert consensus pathway explicitly states that it is reasonable to use both an SGLT2 inhibitor and a GLP-1RA with demonstrated cardiovascular benefit concomitantly if clinically indicated, even though such combination therapy has not been extensively studied specifically for cardiovascular disease risk reduction 1.

This recommendation is supported by:

• The DURATION-8 trial demonstrated that the combination of an SGLT2 inhibitor (dapagliflozin) with a GLP-1RA (exenatide) produced greater reductions in blood pressure and body weight than either agent alone 1
• The non-glycemic effects of these medication classes appear to be additive 1
• Current type 2 diabetes management guidelines support combination therapy with both an SGLT2 inhibitor and a GLP-1RA for glycemic management 1

Cardiovascular Benefits of Each Agent

SGLT2 Inhibitors (Jardiance/Empagliflozin)

• Empagliflozin is specifically recommended for patients with T2DM and cardiovascular disease to reduce the risk of death 1
• Reduces cardiovascular mortality by 38% and hospitalization for heart failure by 35% in patients with established cardiovascular disease 2, 3
• Provides significant renal protection 2

GLP-1 RAs (Ozempic/Semaglutide)

• Semaglutide is recommended in patients with T2DM and cardiovascular disease, or at very high/high CV risk, to reduce CV events 1
• Provides significant weight loss benefits (5.17 kg with 1.0 mg dose) 4
• Achieves greater HbA1c reduction compared to insulin glargine (1.64% vs 0.83%) 4

Monitoring and Management Considerations

When using this combination:

1. Monitor for hypoglycemia: While both agents have a low inherent risk of hypoglycemia, dose adjustment of other glucose-lowering medications may be required, particularly insulin or sulfonylureas 1, 2

2. Watch for side effects:

   • Genital mycotic infections (more common with SGLT2 inhibitors) 1, 2, 3
   • Gastrointestinal symptoms (more common with GLP-1RAs) 4
   • Volume depletion/hypotension (with SGLT2 inhibitors) 2, 5
   • Euglycemic diabetic ketoacidosis (rare but serious risk with SGLT2 inhibitors) 1, 2

3. Patient education: Inform patients about:

   • The risk of genital mycotic infections and importance of personal hygiene 1
   • Symptoms of diabetic ketoacidosis requiring immediate medical attention 1
   • Expected gastrointestinal side effects with semaglutide that typically improve over time

Practical Implementation

• Start with one agent, stabilize the patient, then add the second agent
• Consider starting with the agent that addresses the patient's most pressing clinical need (cardiovascular risk, weight management, glycemic control)
• The 2024 ESC guidelines for peripheral arterial and aortic diseases recommend both SGLT2 inhibitors and GLP-1RAs with proven CV benefit for patients with T2DM, independent of baseline or target HbA1c and concomitant glucose-lowering medication 1

Caveats and Considerations

• Cost may be a significant barrier as both medications are expensive 2
• The combination has not been extensively studied specifically for cardiovascular disease risk reduction, though individual components have proven benefits 1
• Mechanistically, these drug classes have opposite effects on glucagon, suggesting the possibility of an interaction, though clinical evidence suggests benefits outweigh theoretical concerns 1

This combination represents a modern approach to diabetes management that addresses multiple pathophysiological mechanisms while providing cardiovascular and renal protection beyond glycemic control.