Can you take Mounjaro (tirzepatide) and Jardiance (empagliflozin) at the same time?

Can You Take Mounjaro and Jardiance at the Same Time?

Yes, you can safely take Mounjaro (tirzepatide) and Jardiance (empagliflozin) together—this combination is not only safe but often clinically beneficial for patients with type 2 diabetes, as these medications work through complementary mechanisms without significant drug interactions. 1, 2

Complementary Mechanisms of Action

• Tirzepatide is a dual GIP/GLP-1 receptor agonist that enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and promotes significant weight loss (up to 20.9% body weight reduction in clinical trials). 3, 4

• Empagliflozin is an SGLT2 inhibitor that works independently by blocking glucose reabsorption in the kidneys, promoting urinary glucose excretion, and providing cardiovascular and renal protection beyond glycemic control. 1, 5

• These mechanisms do not overlap, meaning there is no pharmacological reason to avoid combining them, and the combination may provide additive benefits for glycemic control, weight management, and cardiovascular/renal protection. 1

Clinical Benefits of Combination Therapy

For glycemic control:

• The 2024 ADA Standards of Care recommend dual-combination therapy when A1C is ≥1.5% above goal, and both tirzepatide and SGLT2 inhibitors are preferred agents with complementary glucose-lowering effects. 1
• Tirzepatide provides superior glycemic control compared to GLP-1 RAs alone (HbA1c reductions of 2.0-2.5%), while empagliflozin adds an additional 0.5% HbA1c reduction through its independent renal mechanism. 1, 3

For cardiovascular and renal protection:

• Empagliflozin reduces cardiovascular death by 38% and heart failure hospitalization by 35%, with benefits extending to patients with eGFR as low as 20 mL/min/1.73 m². 5, 6
• GLP-1-based therapies (the class to which tirzepatide belongs) provide favorable cardiovascular outcomes and are recommended early in treatment algorithms. 1, 4

For weight management:

• Tirzepatide has the highest weight loss efficacy among glucose-lowering agents (mean weight change up to -20.9%), while empagliflozin provides modest additional weight loss through its diuretic effect. 1, 3

Safety Considerations When Using Both Medications

Hypoglycemia risk:

• Both medications have a low risk of hypoglycemia when used together, as neither stimulates insulin release in a glucose-independent manner. 1, 3
• If the patient is also taking insulin or sulfonylureas, those medications may need dose reduction when adding either tirzepatide or empagliflozin. 1

Gastrointestinal side effects:

• Tirzepatide commonly causes nausea, diarrhea, decreased appetite, and vomiting (mostly mild to moderate), which are consistent with GLP-1 RA class effects. 3, 4
• These GI effects are not worsened by empagliflozin, which has a different side effect profile focused on genital mycotic infections (6% vs 1% placebo) and urinary tract infections. 2, 5

Volume depletion:

• Empagliflozin causes intravascular volume contraction through diuretic and natriuretic effects, which may be relevant in patients on concurrent diuretics or with low systolic blood pressure. 7, 5
• Tirzepatide does not have significant diuretic effects, so the combination does not substantially increase volume depletion risk beyond empagliflozin alone. 3

Diabetic ketoacidosis (DKA):

• Empagliflozin carries a risk of euglycemic DKA, particularly during acute illness, reduced food intake, or surgical procedures. 5, 8
• Withhold empagliflozin during acute illness with reduced food/fluid intake, fever, vomiting, or diarrhea, and discontinue at least 3 days before major surgery. 7, 5
• Tirzepatide does not increase DKA risk, but patients should be educated about the specific risk from empagliflozin. 3, 8

Renal Function Considerations

Empagliflozin dosing with renal impairment:

• Continue empagliflozin 10 mg daily for cardiovascular/renal protection even when eGFR falls to 20-44 mL/min/1.73 m², though glucose-lowering efficacy diminishes below 45 mL/min/1.73 m². 2, 5
• Do NOT discontinue empagliflozin solely because eGFR drops below 45 mL/min/1.73 m², as cardiovascular death and heart failure hospitalization reduction persist at lower eGFR levels. 5

Tirzepatide with renal impairment:

• Tirzepatide can be used across the spectrum of renal function without dose adjustment, as it is not primarily renally cleared. 3, 4

Practical Algorithm for Combined Use

1. Initiate empagliflozin 10 mg once daily for cardiovascular/renal protection if eGFR ≥25 mL/min/1.73 m² (or ≥20 mL/min/1.73 m² per some guidelines). 2, 5

2. Start tirzepatide at 2.5 mg subcutaneously once weekly, titrating every 4 weeks (2.5 mg → 5 mg → 7.5 mg → 10 mg → 12.5 mg → 15 mg) based on glycemic response and tolerability. 3, 4

3. Monitor eGFR within 1-2 weeks after starting empagliflozin, then every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if ≥60 mL/min/1.73 m². 2, 5

4. Assess for genital mycotic infections (empagliflozin-related) and gastrointestinal symptoms (tirzepatide-related) at follow-up visits. 2, 5, 3

5. Educate patients to withhold empagliflozin during acute illness and to stop it 3 days before surgery, while continuing tirzepatide unless unable to maintain oral intake. 7, 5

Common Pitfalls to Avoid

• Do not reduce insulin or sulfonylurea doses preemptively when starting this combination unless glucose levels are already near target, as both medications have low hypoglycemia risk when used without insulin secretagogues. 1, 2

• Do not discontinue empagliflozin when eGFR falls below 45 mL/min/1.73 m² in patients already taking it, as the cardiovascular and renal benefits continue even when glycemic efficacy is lost. 2, 5

• Do not overlook sick day management education for empagliflozin, as failure to withhold during acute illness significantly increases euglycemic DKA risk. 5, 8

• Do not assume GI side effects from tirzepatide are worsened by empagliflozin—these are independent side effect profiles that do not interact. 3