Can a Patient Take Rybelsus and Jardiance Together?
Yes, a patient with type 2 diabetes can safely take Rybelsus (semaglutide) and Jardiance (empagliflozin) together, and this combination is explicitly supported by current guidelines for patients with cardiovascular disease or chronic kidney disease. 1
Guideline Support for Combination Therapy
The 2025 ADA Standards of Care explicitly recommend combining SGLT2 inhibitors (like Jardiance) with GLP-1 receptor agonists (like Rybelsus) as part of comprehensive glucose-lowering regimens for patients with type 2 diabetes. 1
For patients with established cardiovascular disease or high cardiovascular risk, both medications should be used together independent of A1C levels and independent of metformin use. 1
The European Society of Cardiology recommends empagliflozin (Jardiance) for patients with type 2 diabetes and CVD to reduce cardiovascular events and death, while also recommending semaglutide (the active ingredient in Rybelsus) for the same population. 1, 2
Specific Clinical Scenarios Where This Combination Is Recommended
Heart Failure: If the patient has heart failure (either reduced or preserved ejection fraction), Jardiance is specifically recommended regardless of A1C level, and can be combined with Rybelsus. 1
Chronic Kidney Disease: For patients with CKD (eGFR 20-60 mL/min/1.73 m² or albuminuria), both medications provide kidney protection and should be used together for slowing CKD progression. 1
Cardiovascular Disease: Patients with established atherosclerotic cardiovascular disease benefit from both medications simultaneously for cardiovascular risk reduction. 1, 2
Evidence from Clinical Research
A 2024 randomized trial directly studied the combination of semaglutide and empagliflozin in 80 patients with type 2 diabetes and high cardiovascular risk, demonstrating safety and tolerability of the combination over 32 weeks. 3, 4
The combination therapy resulted in a 5% reduction in total kidney volume compared to placebo, suggesting additive renal benefits. 3
No unexpected safety signals emerged from combination therapy in these trials. 3, 4
Important Safety Considerations
Hypoglycemia Risk: Both medications have minimal hypoglycemia risk when used together, as both work through insulin-independent mechanisms. 1 However, if the patient is also taking insulin or sulfonylureas, reduce insulin dose by approximately 20% and consider stopping sulfonylureas when initiating this combination. 5
Volume Depletion: Jardiance can cause volume depletion and orthostatic hypotension, particularly when combined with diuretics. Monitor for signs of dehydration and consider reducing diuretic doses if volume contraction occurs. 1, 5
Genital Infections: Both medications can increase risk of genital mycotic infections, with the risk being additive. Provide patient education about hygiene and early recognition. 6, 7
Diabetic Ketoacidosis: Jardiance carries a risk of euglycemic DKA. Discontinue at least 3 days before planned surgery and educate patients to stop the medication during acute illness, vomiting, or severe dehydration. 1, 5
Gastrointestinal Effects: Rybelsus commonly causes nausea and may cause constipation. Two cases of semaglutide-associated obstipation were reported in combination therapy trials. 4
Dosing Recommendations
Jardiance: Start at 10 mg daily, can increase to 25 mg daily if tolerated and additional glycemic control needed. 5
Rybelsus: Start at 3 mg daily for 30 days, then increase to 7 mg daily; can further increase to 14 mg daily if needed for glycemic control. 1
Both medications can be initiated simultaneously in treatment-naive patients to shorten time to glycemic goal achievement. 1
Renal Function Monitoring
Jardiance is effective until eGFR falls below 45 mL/min/1.73 m², at which point glycemic efficacy is reduced but cardiovascular and renal benefits persist down to eGFR 20 mL/min/1.73 m². 1, 6
Monitor renal function periodically, as both medications can cause transient GFR reductions that are generally hemodynamic rather than indicative of kidney injury. 3, 4