What additional medication can be used in a patient currently on Janumet (sitagliptin and metformin) who has not tolerated Ozempic (semaglutide) or Jardiance (empagliflozin)?

Additional Medication Options for a Patient on Janumet Who Has Not Tolerated Ozempic or Jardiance

Recommended Medication Option

A thiazolidinedione (TZD) like pioglitazone is the most appropriate additional medication for a patient currently on Janumet (sitagliptin/metformin) who has not tolerated Ozempic (semaglutide) or Jardiance (empagliflozin). 1

Understanding the Current Medication

• Janumet is a fixed-dose combination of sitagliptin (a DPP-4 inhibitor) and metformin (a biguanide) that works by potentiating insulin secretion, reducing glucagon secretion, and decreasing hepatic glucose production 2
• This combination improves glucose control without inducing hypoglycemia or weight gain, with side effects primarily related to the metformin component 2

Rationale for Medication Selection

Why a Thiazolidinedione (TZD):

• For patients who have not achieved glycemic targets on metformin and DPP-4 inhibitor therapy (Janumet), adding an agent with a complementary mechanism of action is recommended 1
• TZDs like pioglitazone have possible cardiovascular benefits, especially in individuals with or at high risk for stroke 1
• Pioglitazone can be effectively combined with DPP-4 inhibitors and metformin, providing complementary mechanisms of action 3
• TZDs may be particularly beneficial in patients with nonalcoholic fatty liver disease (NAFLD) at high risk of fibrosis 1

Why Not Other Options:

• GLP-1 receptor agonists (like Ozempic/semaglutide) have already been tried and not tolerated by the patient 1
• SGLT2 inhibitors (like Jardiance/empagliflozin) have already been tried and not tolerated by the patient 1
• Combining another DPP-4 inhibitor with Janumet would be redundant as Janumet already contains sitagliptin (a DPP-4 inhibitor) 1
• Sulfonylureas are associated with a higher risk of adverse events and death when combined with metformin compared to the combination of metformin and a DPP-4 inhibitor 1

Important Considerations and Monitoring

Precautions with TZD Therapy:

• TZDs are not recommended in patients with diabetes and symptomatic heart failure 1
• Monitor for fluid retention, weight gain, and signs of heart failure 1
• Baseline and periodic liver function tests should be performed 1
• Consider bone health, as TZDs may increase fracture risk in some patients 1

Alternative Options If TZDs Are Contraindicated:

• Basal insulin therapy may be considered if the patient has no contraindications 1
• Insulin may be considered in patients with advanced systolic heart failure with reduced ejection fraction (HFrEF) 1
• For patients requiring insulin, consider starting with a conservative dose to avoid hypoglycemia, especially if renal function is impaired 1

Special Considerations

• If the patient has chronic kidney disease (CKD) with eGFR <45 ml/min/1.73m², dose adjustments for metformin in Janumet would be required 1
• If the patient has cardiovascular disease, carefully weigh the benefits and risks of TZDs, as they may increase the risk of heart failure in susceptible individuals 1
• For patients with a history of stroke, pioglitazone may offer additional benefits 1

Conclusion for Clinical Practice

• Start with pioglitazone at a low dose and titrate based on glycemic response and tolerability 1
• Reassess glycemic control after 3 months of combination therapy 1
• If glycemic targets are still not met after adding a TZD, consider transitioning to insulin therapy 1
• Maintain the patient on Janumet while adding the TZD, as continuing metformin when used in combination with other agents is recommended if tolerated and not contraindicated 1