What are the potential interactions between Trulicity (dulaglutide) and Jardiance (empagliflozin)?

Trulicity and Jardiance: Drug Interaction Profile

Trulicity (dulaglutide) and Jardiance (empagliflozin) can be safely used in combination with no significant direct pharmacological interactions, and this combination may provide complementary benefits for glycemic control, cardiovascular risk reduction, and weight management.

Mechanism of Action and Complementary Effects

• Trulicity (dulaglutide): A GLP-1 receptor agonist that stimulates insulin secretion and reduces glucagon secretion in a glucose-dependent manner, improves satiety, and promotes weight loss 1.

• Jardiance (empagliflozin): An SGLT2 inhibitor that works by preventing glucose reabsorption in the kidneys, leading to increased urinary glucose excretion 1.

These medications work through different and complementary mechanisms:

• GLP-1 RAs like dulaglutide have high glucose-lowering efficacy with minimal risk of hypoglycemia when used alone 1
• SGLT2 inhibitors like empagliflozin have moderate glucose-lowering effects but provide cardiovascular and renal benefits 1

Safety Profile of Combination Therapy

The combination of these medications does not have any significant direct pharmacological interactions. However, there are several important considerations:

Potential Additive Effects:

1. Hypoglycemia risk:

   • Both medications individually have low risk of hypoglycemia 1
   • When combined, they maintain this favorable profile unless used with insulin or sulfonylureas

2. Blood pressure effects:

   • Empagliflozin has diuretic effects that can lead to volume depletion and blood pressure reduction 1
   • Monitor for orthostatic hypotension, especially in patients taking other antihypertensive medications

3. Gastrointestinal effects:

   • Dulaglutide commonly causes GI side effects (nausea, vomiting, diarrhea) 2
   • These effects may be exacerbated when combined with the fluid loss from empagliflozin

Specific Precautions:

• Dehydration risk: SGLT2 inhibitors can cause dehydration, which may be worsened if dulaglutide causes GI side effects like vomiting or diarrhea 1

• Diabetic ketoacidosis (DKA):

  • SGLT2 inhibitors have been associated with euglycemic DKA 1
  • While rare, there have been case reports of GLP-1 RAs like dulaglutide also being associated with euglycemic DKA 3
  • The combination requires careful monitoring, especially in insulin-deficient patients

• Renal function:

  • Both medications have different considerations for renal impairment
  • Dulaglutide maintains efficacy across different eGFR levels 2
  • Empagliflozin's glucose-lowering effect diminishes with declining eGFR 1

Cardiovascular and Renal Benefits

The combination may provide additive cardiovascular and renal benefits:

• Empagliflozin has been shown to reduce cardiovascular mortality and heart failure hospitalizations 1
• Dulaglutide demonstrated significant reduction in major adverse cardiac events (MACE) in the REWIND trial 4
• Both medications have shown renal protective effects 1, 2

Clinical Decision-Making Algorithm

1. Assess baseline status:

   • Check renal function (eGFR)
   • Evaluate cardiovascular risk factors
   • Assess hydration status and blood pressure

2. Initiation strategy:

   • Start with one medication and stabilize before adding the second
   • Begin with lower doses and titrate gradually
   • Monitor for dehydration, hypotension, and GI effects during initiation

3. Monitoring recommendations:

   • Regular assessment of renal function
   • Blood pressure monitoring
   • Education on signs of dehydration and DKA
   • Weight and glycemic monitoring

Patient Education Points

• Ensure adequate hydration, especially during illness
• Recognize and report symptoms of dehydration, hypotension, or ketoacidosis
• Temporary discontinuation may be needed during severe illness, vomiting, or dehydration 1
• Monitor blood glucose regularly, especially when starting therapy

Summary

The combination of Trulicity and Jardiance does not have significant direct pharmacological interactions and may provide complementary benefits for glycemic control, cardiovascular protection, and weight management. However, careful monitoring for potential additive effects on volume status and awareness of the rare risk of euglycemic DKA is important for safe use of this combination.