Can a patient with type 2 diabetes take Jardiance (empagliflozin) and Ozempic (semaglutide) together?

Combining Jardiance (Empagliflozin) and Ozempic (Semaglutide) in Type 2 Diabetes

Yes, patients with type 2 diabetes can safely and effectively take both Jardiance (empagliflozin) and Ozempic (semaglutide) together, as these medications work through complementary mechanisms and have demonstrated cardiovascular benefits.

Rationale for Combination Therapy

• Both medications belong to different drug classes with distinct mechanisms of action:

  • Jardiance (empagliflozin): SGLT2 inhibitor that increases urinary glucose excretion
  • Ozempic (semaglutide): GLP-1 receptor agonist that enhances insulin secretion and suppresses glucagon

• The American College of Cardiology recommends using both an SGLT2 inhibitor and a GLP-1 receptor agonist concomitantly when clinically indicated, particularly for patients with established cardiovascular disease 1

Clinical Benefits of Combination

Glycemic Control

• Both medications provide complementary HbA1c reduction:
  • Empagliflozin: 0.7-1.0% reduction 1
  • Semaglutide: 0.8-1.5% reduction 1

Cardiovascular Benefits

• Both medications have demonstrated cardiovascular benefits in large clinical trials:
  • Empagliflozin reduced cardiovascular death, hospitalization for heart failure, and all-cause mortality in the EMPA-REG OUTCOME trial 2, 1
  • Semaglutide reduced the risk of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% in the SUSTAIN-6 trial 2

Renal Benefits

• Empagliflozin has shown significant renal protective effects:

  • Reduced risk of incident or worsening nephropathy by 39% 2
  • Reduced risk of doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73 m² by 44% 2

• Semaglutide has also demonstrated renal benefits:

  • Reduced risk of new or worsening nephropathy by 36% 2

Monitoring and Precautions

• When combining these medications, monitor for:

  • Hypoglycemia: Dose adjustment of other glucose-lowering medications may be required 1
  • Volume depletion/hypotension: Both medications can affect fluid balance 1
  • Genital mycotic infections: Common with SGLT2 inhibitors 1
  • Gastrointestinal symptoms: Common with GLP-1 receptor agonists 1
  • Euglycemic diabetic ketoacidosis: Risk with empagliflozin 1

• Temporarily discontinue empagliflozin when undergoing procedures with iodinated contrast agents 1

Recent Comparative Evidence

• A 2025 target trial emulation study comparing semaglutide versus empagliflozin showed:

  • Semaglutide had a trend toward greater reduction in the composite outcome of death, MI, or stroke (HR 0.89,95% CI 0.78-1.02)
  • Semaglutide significantly reduced stroke risk (HR 0.62,95% CI 0.43-0.89) 3

• Another 2025 study (SEMPA18) found:

  • Empagliflozin produced more pronounced improvements in albuminuria
  • Semaglutide showed a trend toward greater weight loss 4

Conclusion

The combination of Jardiance (empagliflozin) and Ozempic (semaglutide) is supported by current guidelines and evidence, particularly for patients with established cardiovascular disease or high cardiovascular risk. The medications work through complementary mechanisms and provide additive benefits for glycemic control, cardiovascular outcomes, and renal protection.