Can you take Januvia (sitagliptin) and Synjardy (empagliflozin and metformin) together?

Combining Januvia (Sitagliptin) and Synjardy (Empagliflozin/Metformin)

Yes, Januvia (sitagliptin) and Synjardy (empagliflozin/metformin) can be safely taken together as part of a triple therapy regimen for type 2 diabetes management.

Rationale for Combination Therapy

• Type 2 diabetes is a progressive disease that often requires combination therapy as maintenance of glycemic targets with monotherapy or dual therapy becomes insufficient over time 1
• Each additional medication class typically provides an additional 0.7-1.0% reduction in HbA1c when added to existing therapy 1
• Triple therapy combining different mechanisms of action (DPP-4 inhibitor, SGLT2 inhibitor, and metformin) can provide more robust glycemic control in patients with inadequate response to two medications 1

Pharmacological Considerations

• Sitagliptin (Januvia) is a DPP-4 inhibitor that works by increasing incretin levels, which inhibit glucagon release and increase insulin secretion 2
• Synjardy combines empagliflozin (an SGLT2 inhibitor) with metformin (a biguanide) 3
• These medications work through different and complementary mechanisms:
  • Metformin decreases hepatic glucose production and improves insulin sensitivity 4
  • Empagliflozin reduces plasma glucose by enhancing urinary glucose excretion 4
  • Sitagliptin increases insulin secretion and decreases glucagon secretion in a glucose-dependent manner 2

Evidence Supporting Triple Therapy

• The American Diabetes Association recommends that metformin should be continued as the foundation of therapy when adding second and third agents 5
• When dual therapy fails to maintain glycemic control, triple therapy may be necessary, particularly in patients with higher baseline HbA1c levels 1
• The combination of empagliflozin and metformin has been shown to improve glucose control with minimal risk of hypoglycemia while reducing body weight and blood pressure 3, 6
• Adding sitagliptin to this combination provides complementary effects through a different mechanism of action 2

Safety Considerations

• No significant drug-drug interactions have been reported between sitagliptin and the components of Synjardy 3, 2
• The risk of hypoglycemia is low with this combination unless used with insulin or insulin secretagogues 4
• When using multiple agents, dose adjustment of medications may be required to avoid hypoglycemia, particularly in patients at or near glycemic goals 4
• Regular monitoring of HbA1c every 3-6 months is recommended to assess efficacy 1

Special Populations and Precautions

• For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, empagliflozin (in Synjardy) has demonstrated cardiovascular benefits 4
• Caution is advised in elderly patients and those with impaired renal function 3
• Empagliflozin should not be used in patients with eGFR <45 mL/min/1.73m² 4
• Monitor for vitamin B12 deficiency with long-term metformin use, especially in patients with anemia or peripheral neuropathy 5

Potential Side Effects to Monitor

• Genital mycotic infections (from empagliflozin) 4
• Rare risk of euglycemic diabetic ketoacidosis (from empagliflozin) 4
• Gastrointestinal effects (from metformin) 4
• Upper respiratory tract infections (from sitagliptin) 2

Follow-up Recommendations

• Treatment efficacy should be assessed within approximately 3 months of therapy initiation 4
• If glycemic targets are not met, therapy should be further intensified or adjusted 4
• Regular monitoring for medication-specific adverse effects is essential 4

This triple therapy approach combining Januvia with Synjardy represents a comprehensive strategy targeting multiple pathophysiological defects in type 2 diabetes, potentially offering improved glycemic control through complementary mechanisms of action.