Is it safe to use Trulicity (dulaglutide), a Glucagon-like peptide-1 (GLP-1) receptor agonist, with Farxiga (dapagliflozin)?

Safety of Combining Trulicity (Dulaglutide) with Farxiga (Dapagliflozin)

Yes, it is safe and often recommended to use Trulicity (dulaglutide) with Farxiga (dapagliflozin) in patients with type 2 diabetes, particularly those with established cardiovascular disease, chronic kidney disease, or heart failure. This combination is explicitly supported by major diabetes guidelines and represents complementary mechanisms of action that address different aspects of cardiovascular and renal protection 1.

Guideline Support for Combination Therapy

The ADA/KDIGO consensus explicitly recommends adding a long-acting GLP-1 receptor agonist (like dulaglutide) for patients not achieving glycemic targets despite SGLT2 inhibitor (like dapagliflozin) therapy, or vice versa 1. The 2020 ADA/EASD consensus states that the decision to treat with either a GLP-1 receptor agonist or SGLT2 inhibitor should be considered independently of baseline HbA1c, and both classes can be used together when indicated 1.

Complementary Benefits

• GLP-1 receptor agonists (dulaglutide) are preferred when major adverse cardiovascular events (MACE) reduction is the primary goal, particularly in patients with established atherosclerotic cardiovascular disease 1
• SGLT2 inhibitors (dapagliflozin) provide superior benefits for heart failure hospitalization reduction and chronic kidney disease progression, especially in patients with heart failure with reduced ejection fraction or CKD 1
• Combined use allows patients to benefit from both cardiovascular risk reduction pathways simultaneously 1

Specific Clinical Scenarios Supporting Combination

Chronic Kidney Disease

Both medications can be used together in CKD patients 1:

• Dulaglutide requires no dose adjustment across all stages of CKD 1
• Dapagliflozin can be initiated at 10 mg daily with eGFR ≥25 mL/min/1.73 m² and continued until dialysis for kidney and cardiovascular benefit 1
• The AWARD-7 trial demonstrated dulaglutide's safety and efficacy in moderate-to-severe CKD (stages 3-4), with reduced eGFR decline 2

Heart Failure

The European Society of Cardiology guidelines note that GLP-1 receptor agonists and SGLT2 inhibitors have neutral to beneficial effects on heart failure risk and may be considered together 1. Dapagliflozin reduces heart failure hospitalization risk by 27% in patients with type 2 diabetes 3, while dulaglutide reduces MACE by 12% 1.

High Cardiovascular Risk

For patients aged ≥55 years with indicators of high cardiovascular risk (coronary/carotid/peripheral artery stenosis >50%, left ventricular hypertrophy, eGFR <60 mL/min/1.73 m², or albuminuria), both agents are recommended 1.

Safety Considerations When Using Both Medications

Volume Status Monitoring

• Dapagliflozin can contribute to intravascular volume contraction 1, 3
• When initiating dapagliflozin in patients already on dulaglutide, assess volume status and consider reducing diuretic doses if applicable 3
• Correct volume depletion before starting dapagliflozin 3

Gastrointestinal Effects

• Dulaglutide commonly causes nausea (14-20%), vomiting, and diarrhea (16-17%) 4, 2
• These effects are typically transient and diminish over time 4
• No additive gastrointestinal effects are expected when combining with dapagliflozin 5

Hypoglycemia Risk

• Both medications have low intrinsic hypoglycemia risk when used without sulfonylureas or insulin 4, 2
• If patients are on insulin or sulfonylureas, consider reducing those doses when initiating either agent 1
• Dulaglutide reduces symptomatic hypoglycemia compared to insulin (4.3-4.4 vs 9.6 events per patient-year) 2

Renal Function Monitoring

• Assess renal function before initiating dapagliflozin and periodically thereafter 3
• Dapagliflozin causes transient eGFR decreases that return to baseline within 3 weeks of discontinuation 6
• Dulaglutide is associated with preserved or improved eGFR over time in CKD patients 2

Surgical Planning

• Discontinue dapagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1
• No specific surgical precautions are needed for dulaglutide 4

Common Pitfalls to Avoid

Infection Monitoring

• Monitor for genital mycotic infections (6% incidence with SGLT2 inhibitors vs 1% with placebo), which are more common in women 1
• Daily hygienic measures can lessen this risk 1
• Rare cases of Fournier gangrene have been reported with SGLT2 inhibitors 1

Ketoacidosis Awareness

• Educate patients about signs and symptoms of euglycemic diabetic ketoacidosis with dapagliflozin 1
• Patients should discontinue dapagliflozin and seek immediate medical attention if ketoacidosis is suspected 1

Pancreatitis Consideration

• While rare, dulaglutide has been associated with acute pancreatitis 7
• Monitor for persistent severe abdominal pain radiating to the back 7
• This risk does not contraindicate combination therapy but warrants clinical awareness 7

Amputation Risk

• Patients with foot ulcers or at high risk for amputation should only receive SGLT2 inhibitors after careful shared decision-making with comprehensive foot care education 1

No Pharmacokinetic Interactions

Dapagliflozin shows no clinically relevant drug interactions with other antidiabetic or cardiovascular medications 5. Dulaglutide's metabolism and clearance are independent of renal function 4, 2. These medications can be safely combined without dose adjustments based on their pharmacokinetic profiles 5, 4.