Can you take Januvia (Sitagliptin) with Synjardy (Empagliflozin/Metformin)?

Combining Januvia with Synjardy in Type 2 Diabetes Management

Yes, Januvia (sitagliptin) can be safely combined with Synjardy (empagliflozin/metformin) for type 2 diabetes management, as they have complementary mechanisms of action and no contraindicated drug interactions.

Medication Mechanisms and Compatibility

Januvia (sitagliptin) and Synjardy (empagliflozin/metformin) work through different mechanisms:

• Januvia (sitagliptin): A DPP-4 inhibitor that increases insulin secretion and reduces glucagon secretion in a glucose-dependent manner 1
• Synjardy components:
  • Empagliflozin: An SGLT2 inhibitor that reduces glucose by inhibiting renal tubular glucose reabsorption 1
  • Metformin: A biguanide that decreases hepatic glucose production and improves insulin sensitivity 1

Evidence Supporting This Combination

The American Diabetes Association and European Association for the Study of Diabetes support combining these medication classes:

• DPP-4 inhibitors like sitagliptin have moderate glucose-lowering efficacy, are well tolerated, have a neutral effect on weight, and minimal risk of hypoglycemia when used as monotherapy 1
• SGLT2 inhibitors like empagliflozin can reduce HbA1c by 0.5-1.0%, reduce body weight by 1.5-3.5 kg, and lower systolic blood pressure 1
• Metformin remains the preferred first-line medication for type 2 diabetes management due to its efficacy, safety, and low cost 1

Benefits of This Combination

1. Complementary mechanisms: These medications target different pathways in glucose regulation, potentially offering additive glycemic control 2

2. Cardiovascular and renal benefits:

   • SGLT2 inhibitors reduce cardiovascular events, heart failure hospitalizations, and CKD progression 2
   • This combination is particularly beneficial for patients with or at risk for cardiovascular disease or CKD 2

3. Low hypoglycemia risk: When used together, these medications have minimal risk of hypoglycemia compared to sulfonylureas or insulin 1

4. Weight effects:

   • SGLT2 inhibitors promote weight loss
   • DPP-4 inhibitors are weight-neutral
   • This combination avoids the weight gain associated with some other diabetes medications 1

Important Considerations

1. Renal function monitoring:

   • Empagliflozin's glucose-lowering efficacy decreases when eGFR falls below 45 mL/min/1.73 m² 2
   • Metformin should not be started in those with eGFR <45 mL/min/1.73 m² and should be stopped when eGFR is <30 mL/min/1.73 m² 1

2. Side effect awareness:

   • SGLT2 inhibitors: Increased risk of genitourinary infections; rare risk of diabetic ketoacidosis 1, 2
   • Metformin: Gastrointestinal side effects; rare risk of lactic acidosis 1
   • Sitagliptin: Generally well-tolerated with minimal side effects 3

3. Contraindicated combinations:

   • Do not combine GLP-1 receptor agonists with DPP-4 inhibitors (like sitagliptin) as there is no added glucose-lowering benefit 1

Clinical Approach

When considering adding Januvia to Synjardy therapy:

1. Assess glycemic control: If A1C remains above target despite Synjardy therapy, adding Januvia is appropriate

2. Evaluate cardiovascular and renal status: This combination is particularly beneficial for patients with established ASCVD, high ASCVD risk, heart failure, or CKD 2

3. Monitor efficacy: Evaluate A1C after approximately 3 months of combined therapy 2

4. Adjust therapy as needed: If glycemic targets are not achieved after 3 months, consider alternative or additional therapy options 2

Common Pitfalls to Avoid

1. Overlooking renal function: Always assess renal function before initiating or continuing this combination therapy

2. Ignoring infection risk: Educate patients about increased risk of genital mycotic infections with SGLT2 inhibitors 2

3. Failing to monitor B12 levels: Long-term metformin use may be associated with vitamin B12 deficiency 1

4. Overlooking symptoms of ketoacidosis: Patients should be educated about symptoms of euglycemic diabetic ketoacidosis 2

This triple therapy approach offers complementary mechanisms of action with potential cardiovascular and renal benefits while minimizing hypoglycemia risk and avoiding weight gain.