Can Jardiance and Ozempic Be Used Together?
Yes, patients can and often should be on Jardiance (empagliflozin) and Ozempic (semaglutide) simultaneously, as these medications work through complementary mechanisms and are explicitly recommended together by major guidelines for patients with type 2 diabetes, particularly those with cardiovascular disease, heart failure, or chronic kidney disease. 1
Guideline-Based Rationale for Combination Therapy
The American Diabetes Association explicitly supports combining SGLT2 inhibitors (like Jardiance) with GLP-1 receptor agonists (like Ozempic) as part of evidence-based treatment regimens. 2 This combination is particularly recommended because:
- For patients with established cardiovascular disease, both drug classes should be prescribed together to reduce cardiovascular events 1
- For patients with heart failure (both HFrEF and HFpEF), SGLT2 inhibitors provide proven benefits and can be safely combined with GLP-1 RAs 1
- For patients with chronic kidney disease, both medications independently slow kidney disease progression and are recommended for concurrent use 1
The 2019 ESC Guidelines on Diabetes and Cardiovascular Disease specifically recommend empagliflozin, canagliflozin, or dapagliflozin in patients with type 2 diabetes and CVD to reduce cardiovascular events, while also recommending liraglutide, semaglutide, or dulaglutide for the same population 2. These recommendations support using both drug classes simultaneously rather than choosing one over the other.
Complementary Mechanisms of Action
The combination provides additive benefits through distinct pathways:
- Ozempic works by stimulating insulin secretion in a glucose-dependent manner, reducing glucagon, improving satiety, and promoting weight loss 1
- Jardiance works by inducing urinary glucose excretion through SGLT2 inhibition, independent of insulin pathways 3
- The combination provides complementary cardiovascular protection through different mechanisms 1
Safety Profile of the Combination
The combination has an excellent safety profile with low hypoglycemia risk since neither medication depends on insulin secretion when used without sulfonylureas or insulin. 1
Clinical trial data specifically examining this combination demonstrates:
- In a 52-week Japanese study, empagliflozin added to liraglutide (a GLP-1 RA similar to semaglutide) was well tolerated with only 9.4-21.2% of patients reporting drug-related adverse events 3
- The combination led to clinically meaningful improvements in HbA1c (-0.55% to -0.77%), body weight (-2.6 to -3.1 kg), and blood pressure (-6.7 to -8.4 mmHg systolic) 3
- A recent 18-month real-world cohort study showed both medications improved glycemic control, with empagliflozin producing more pronounced improvements in albuminuria while semaglutide showed trends toward greater weight loss 4
Practical Implementation
Start both medications simultaneously or sequentially with no washout period required. 1
Ozempic Initiation:
- Begin at 0.25 mg subcutaneously once weekly for 4 weeks to minimize gastrointestinal effects 1
- Increase to 0.5 mg weekly as the maintenance dose for most patients 1
Jardiance Dosing:
- Standard doses are 10 mg or 25 mg once daily 3
Monitoring Requirements:
- Check eGFR at baseline and at least annually if eGFR ≥60 mL/min/1.73m² 1
- Monitor every 3-6 months if eGFR 30-59 mL/min/1.73m² 1
- Monitor for volume depletion and ensure adequate hydration, especially when starting therapy 1
Critical Pitfalls to Avoid
Do not withhold combination therapy while waiting to reach "target doses" of one medication before adding the other—guidelines explicitly state this is unnecessary. 1
Do not discontinue Jardiance due to modest initial eGFR decline (2-4 mL/min drop is expected and hemodynamically mediated, with long-term nephroprotective benefits). 1 This initial dip represents favorable hemodynamic changes, not kidney injury.
Do not use Jardiance if eGFR <25 mL/min/1.73m² for glycemic control (though it may still be used for heart failure indications at lower eGFR). 1
Discontinue Jardiance 3-4 days before scheduled surgery to reduce the risk of perioperative ketoacidosis. 5 This temporary interruption does not compromise the drug's overall therapeutic value but is a necessary safety measure. 5
Additional Considerations
Recent MRI studies demonstrate that both medications produce microstructural changes in the kidneys, with the combination reducing total kidney volume by 5% compared to placebo, possibly mediated by reduction in hyperfiltration. 6 These changes were associated with improvements in GFR and albuminuria, supporting the renal protective effects of combination therapy. 6
The combination is particularly valuable because it addresses multiple pathophysiologic defects in type 2 diabetes simultaneously while providing cardiovascular and renal protection beyond glucose lowering alone. 2