What medication can be added to metformin (biguanide) and Jardiance (empagliflozin) for a patient with diabetes?

Adding Medication to Metformin and Jardiance (Empagliflozin) for Diabetes

A GLP-1 receptor agonist is the most appropriate medication to add to metformin and empagliflozin (Jardiance) for patients with diabetes requiring additional glycemic control, especially for those with established cardiovascular disease.

Understanding Your Current Regimen

• You are currently on a dual therapy regimen consisting of metformin (a biguanide) and empagliflozin (Jardiance, an SGLT2 inhibitor) 1, 2
• This combination provides complementary mechanisms of action: metformin improves insulin sensitivity and reduces hepatic glucose production, while empagliflozin increases urinary glucose excretion 3
• Type 2 diabetes is progressive, often requiring additional medications over time to maintain glycemic targets 4

Recommended Third Medication Options

First-Line Recommendation: GLP-1 Receptor Agonist

• A GLP-1 receptor agonist should be added as the third agent to your current regimen of metformin and empagliflozin 1
• Benefits of adding a GLP-1 receptor agonist:
  • Provides robust HbA1c reduction (0.7-1.0%) 4
  • Associated with weight loss 1
  • Low risk of hypoglycemia 1
  • Cardiovascular benefits in patients with established cardiovascular disease 1, 4
  • Complementary mechanism to both metformin and empagliflozin 1

Alternative Option: DPP-4 Inhibitor

• A DPP-4 inhibitor (e.g., sitagliptin, linagliptin) could be considered if GLP-1 receptor agonists are not tolerated or contraindicated 4, 5
• Benefits of adding a DPP-4 inhibitor:
  • Moderate HbA1c reduction 5
  • Weight neutral 1
  • Low risk of hypoglycemia 1
  • Oral administration (versus injectable GLP-1 receptor agonists) 5
• Clinical evidence supports the efficacy of triple therapy with empagliflozin, linagliptin, and metformin 5

Other Options to Consider

Sulfonylurea

• Can be added as a third agent, particularly if cost is a major concern 1, 2
• However, sulfonylureas have disadvantages:
  • Associated with weight gain 1
  • Higher risk of hypoglycemia (24% with sulfonylureas vs. 2% with empagliflozin) 6
  • No cardiovascular benefits 1

Thiazolidinedione (e.g., Pioglitazone)

• May be considered as an add-on therapy 7
• Provides additional HbA1c reduction of 0.7-1.0% 7
• However, associated with weight gain and potential fluid retention 1

Special Considerations

For Patients with Cardiovascular Disease

• If you have established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, a GLP-1 receptor agonist with proven cardiovascular benefit is strongly preferred 1, 4
• The combination of metformin, empagliflozin, and a GLP-1 receptor agonist provides complementary cardiovascular protection 1, 8

Monitoring Recommendations

• Regular monitoring of HbA1c every 3-6 months to assess efficacy of the triple therapy 4
• Monitor for potential side effects specific to each medication:
  • Metformin: gastrointestinal effects, vitamin B12 deficiency 1, 7
  • Empagliflozin: genital mycotic infections, volume depletion 2
  • GLP-1 receptor agonists: nausea, vomiting (typically transient) 1

Practical Implementation

• Consider cost and insurance coverage when selecting the third agent 1, 8
• Fixed-dose combinations may be available to reduce pill burden and improve adherence 9
• Stepwise addition of medications is generally preferred over simultaneous initiation of multiple new agents 1

Remember that the selection of the third medication should be based on your specific clinical characteristics, particularly the presence of cardiovascular disease, risk of hypoglycemia, and weight considerations 1.