Can an adult with type 2 diabetes safely take Mounjaro (tirzepatide) together with Jardiance (empagliflozin), and what are the benefits?

Combining Mounjaro and Jardiance in Type 2 Diabetes

Yes, it is not only safe but strongly recommended to use Mounjaro (tirzepatide) and Jardiance (empagliflozin) together in adults with type 2 diabetes, as these medications have complementary mechanisms of action and provide additive benefits for cardiovascular protection, kidney disease prevention, and glycemic control. 1

Why This Combination Is Recommended

The 2025 American Diabetes Association Standards explicitly state that combining an SGLT2 inhibitor (like Jardiance) with a GLP-1 receptor agonist (like Mounjaro) may be considered for additive reduction of cardiovascular and kidney events in patients with established atherosclerotic cardiovascular disease or multiple risk factors. 2 This represents the highest level of guideline support for dual therapy with these medication classes.

Complementary Mechanisms of Action

• Mounjaro works as a dual GIP/GLP-1 receptor agonist, enhancing insulin secretion, suppressing glucagon, slowing gastric emptying, and promoting substantial weight loss (mean reduction 8.47 kg, with up to 67% of patients achieving ≥10% weight reduction). 2, 3

• Jardiance works by blocking glucose reabsorption in the kidneys, lowering blood glucose independently of insulin, and providing direct cardiovascular and renal protective effects through mechanisms beyond glucose lowering. 4, 5

• These medications do NOT have overlapping mechanisms, which is why they can and should be combined—unlike combining two incretin-based therapies (such as Mounjaro with a DPP-4 inhibitor), which provides no additional benefit. 6

Specific Clinical Benefits of the Combination

Cardiovascular Protection

• Both medications independently reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes and established cardiovascular disease. 1
• SGLT2 inhibitors like Jardiance specifically reduce heart failure hospitalizations in both HFrEF and HFpEF, regardless of diabetes status. 1
• GLP-1 receptor agonists like Mounjaro reduce cardiovascular deaths, nonfatal MI, and nonfatal strokes independent of glucose control. 1

Kidney Disease Prevention

• In patients with CKD (eGFR 20-60 mL/min/1.73 m² and/or albuminuria), both an SGLT2 inhibitor and a GLP-1 RA should be used together for slowing CKD progression and reducing cardiovascular events. 1
• Jardiance has proven benefits in reducing CKD progression and cardiovascular events in patients with moderate to severe CKD, even in those without diabetes. 1

Glycemic Control and Weight Loss

• Tirzepatide provides superior glycemic control compared to traditional GLP-1 agonists (HbA1c reductions of 1.87% to 3.02%). 3, 7
• The combination allows for substantial HbA1c reduction without increasing hypoglycemia risk, as neither medication causes hypoglycemia when used together without insulin or sulfonylureas. 2, 5
• Jardiance produces modest additional weight loss (typically 2-3 kg) and blood pressure reduction (3-5 mmHg systolic). 4, 5

Practical Implementation

Starting the Combination

• If a patient is already on metformin with inadequate control, add BOTH Mounjaro and Jardiance simultaneously rather than sequentially, as current guidelines support combination therapy at treatment initiation to shorten time to goal. 1

• If the patient is already on one of these medications, simply add the other without dose adjustment of the existing medication. 1

Monitoring Requirements

• Check eGFR before starting Jardiance and recheck 2-4 weeks after initiation if baseline eGFR is 45-60 mL/min/1.73 m². 4
• Continue eGFR monitoring every 3-6 months thereafter. 4
• Jardiance causes a modest, reversible decrease in eGFR during the first few weeks—this is expected and does not require discontinuation unless eGFR falls persistently below 45 mL/min/1.73 m² (for glycemic purposes). 4
• Monitor for volume depletion signs (orthostatic lightheadedness, dizziness), especially in older adults or those on diuretics. 4

Safety Considerations

• The combination carries minimal hypoglycemia risk when used without insulin or sulfonylureas. 2, 5
• If the patient is also on insulin or sulfonylureas, reduce those medications by 10-20% (insulin) or 50% (sulfonylurea) when adding either Mounjaro or Jardiance to minimize hypoglycemia risk. 2, 4
• Educate patients about genital mycotic infections (≈6% incidence with Jardiance) and gastrointestinal side effects (nausea, diarrhea with Mounjaro, typically mild to moderate). 4, 3
• Withhold Jardiance during prolonged fasting, surgery, or critical illness due to rare risk of euglycemic DKA. 4

Common Pitfalls to Avoid

• Do NOT delay adding the second medication if the patient is not meeting glycemic targets on one medication alone—treatment modification should not be delayed. 2
• Do NOT combine Mounjaro with DPP-4 inhibitors (like Tradjenta/linagliptin), as this provides no additional glucose lowering and is explicitly contraindicated. 6
• Do NOT initiate Jardiance for glycemic purposes if eGFR is <45 mL/min/1.73 m², though it may be continued for cardiovascular/renal protection down to eGFR ≥25 mL/min/1.73 m² if already established. 4
• Do NOT ignore the initial eGFR dip with Jardiance in the first 2-4 weeks—it is typically reversible and expected. 4

When to Prioritize One Over the Other

• In patients with heart failure (HFrEF or HFpEF), prioritize starting Jardiance first due to proven HF hospitalization reduction. 2
• In patients with CKD (eGFR 20-60 mL/min/1.73 m²), prioritize starting Jardiance first due to proven CKD progression reduction. 2
• In patients where weight loss is the primary treatment goal, prioritize starting Mounjaro first due to superior weight loss efficacy. 2
• In patients with established atherosclerotic cardiovascular disease without heart failure or advanced CKD, either medication can be started first, but both should ultimately be used together. 1