What are the guidelines for using Jardiance (empagliflozin) and Cymbalta (duloxetine) together in patients with diabetes and mental health or pain conditions?

Using Jardiance (Empagliflozin) and Cymbalta (Duloxetine) Together in Patients with Diabetes and Neuropathic Pain

Duloxetine (Cymbalta) is recommended as a first-line treatment for diabetic neuropathic pain and can be safely used concurrently with empagliflozin (Jardiance) in patients who have both diabetes and neuropathic pain or depression. 1, 2

Efficacy of Duloxetine for Diabetic Neuropathic Pain

• Duloxetine is a selective serotonin and norepinephrine reuptake inhibitor that is FDA-approved specifically for diabetic peripheral neuropathy 1
• Doses of 60 mg and 120 mg daily have shown efficacy in treating pain associated with diabetic peripheral neuropathy in multiple clinical trials 1, 3
• Approximately 50% of patients achieve at least 50% pain reduction over 12 weeks of treatment, with a Number Needed to Treat (NNT) of 5 for 60 mg/day 2, 3
• Duloxetine not only reduces pain but also improves quality of life and lessens sleep interference in patients with diabetic neuropathy 1

Concurrent Use with Empagliflozin (Jardiance)

• There are no significant drug interactions reported between empagliflozin and duloxetine that would contraindicate their concurrent use 4
• Duloxetine primarily undergoes metabolism via CYP1A2 and CYP2D6 enzymes, while empagliflozin does not significantly affect these pathways 4
• When using both medications together, monitor for:
  • Glycemic control, as duloxetine may cause small increases in HbA1c in some patients with diabetes 5
  • Blood pressure changes, as both medications can affect blood pressure 1

Dosing Considerations

• For diabetic neuropathic pain, start duloxetine at 30 mg daily for one week, then increase to 60 mg daily 1, 2
• Duloxetine can be administered once daily without regard to meals 1
• In older patients (≥65 years), consider starting at lower doses and titrating more slowly due to increased risk of adverse effects, although efficacy remains similar across age groups 6
• Empagliflozin dosing should follow standard recommendations for type 2 diabetes management 1

Special Populations and Precautions

• Hepatic impairment: Duloxetine is contraindicated in patients with hepatic insufficiency 4
• Renal impairment: Severe renal impairment requires caution with duloxetine; empagliflozin efficacy is reduced with declining renal function 1
• Older adults: Higher discontinuation rates due to adverse events are observed in older patients taking duloxetine, though efficacy is maintained 6
• Cardiovascular disease: Monitor patients with cardiovascular comorbidities more closely when using these medications together 1

Potential Adverse Effects

• Common duloxetine side effects include nausea, dizziness, somnolence, constipation, dry mouth, and reduced appetite 3, 7
• Approximately 16% of patients discontinue duloxetine due to adverse effects, with a dose-dependent relationship 3
• Empagliflozin side effects include urinary tract infections, genital mycotic infections, and volume depletion 1
• Monitor for orthostatic hypotension, particularly in patients with diabetic autonomic neuropathy who may already have this condition 1

Alternative Treatment Options

• If duloxetine is not tolerated or ineffective, consider:
  • Pregabalin (also FDA-approved for diabetic neuropathy) 1, 2
  • Gabapentin (effective but not FDA-approved specifically for diabetic neuropathy) 1
  • Amitriptyline or venlafaxine (second-line options) 1, 2

Monitoring Recommendations

• Assess pain reduction using standardized scales at follow-up visits 1
• Monitor glycemic control, as duloxetine may cause small increases in HbA1c in some patients 5
• Evaluate for improvement in quality of life and function, not just pain reduction 1, 3
• Screen for adverse effects at each visit, particularly in the early weeks of treatment 3, 6

Remember that optimizing glycemic control remains fundamental in managing diabetic neuropathy, so appropriate use of empagliflozin for glucose management complements the symptomatic pain relief provided by duloxetine 1, 2.