Should I start with Januvia (sitagliptin) and Farxiga (dapagliflozin) together, or one at a time, for a patient with multiple myeloma on dexamethasone with elevated HbA1C and metformin intolerance?

Management of Steroid-Induced Hyperglycemia in Multiple Myeloma Patient

For a patient with multiple myeloma on dexamethasone with an A1C of 8.5% who did not tolerate metformin, starting with sitagliptin (Januvia) alone is recommended as the first step, followed by adding dapagliflozin (Farxiga) if glycemic targets are not achieved after 3 months.

Rationale for Sequential Approach

Steroid-induced hyperglycemia in multiple myeloma patients requires careful management, balancing glycemic control with treatment tolerability:

• Dexamethasone is a critical component of multiple myeloma treatment regimens and is known to significantly impact glucose metabolism 1
• The patient's inability to tolerate metformin (component of Janumet) necessitates alternative approaches
• A sequential approach allows for:
  • Assessment of individual drug efficacy
  • Better identification of potential side effects
  • Dose titration based on response
  • Minimization of unnecessary polypharmacy

Step 1: Start with Sitagliptin (Januvia) Monotherapy

• Initial recommended dose: 100 mg once daily
• Sitagliptin is well-tolerated with minimal risk of hypoglycemia
• DPP-4 inhibitors like sitagliptin are particularly effective for steroid-induced hyperglycemia as they:
  • Target postprandial glucose excursions common with steroid therapy
  • Have minimal drug interactions with myeloma treatments
  • Do not cause weight gain (important for myeloma patients)

Step 2: Add Dapagliflozin (Farxiga) if Needed

• If A1C remains >7.5% after 3 months on sitagliptin alone, add dapagliflozin 10 mg once daily
• Combination therapy with DPP-4 inhibitors and SGLT2 inhibitors has shown sustained improvements in glycemic control over 52 weeks 2
• This combination provides complementary mechanisms of action:
  • Sitagliptin enhances insulin secretion
  • Dapagliflozin promotes urinary glucose excretion independent of insulin

Special Considerations for Multiple Myeloma Patients

• Monitor renal function regularly, as both multiple myeloma and dapagliflozin can affect kidney function
• Be vigilant for urinary tract and genital infections with dapagliflozin, especially in immunocompromised patients
• Consider bone health, as both multiple myeloma and dapagliflozin can impact bone metabolism
• Maintain adequate hydration to prevent volume depletion with dapagliflozin

Monitoring Recommendations

• Check fasting and postprandial glucose levels weekly during initial therapy
• Reassess A1C after 3 months of sitagliptin monotherapy
• If adding dapagliflozin, monitor for genital mycotic infections and urinary tract infections
• Evaluate renal function at baseline and periodically during treatment

Common Pitfalls to Avoid

• Starting both medications simultaneously may mask individual drug efficacy and side effects
• Overlooking the impact of myeloma treatment cycles on glucose levels
• Failing to adjust diabetes medications during periods of changing steroid doses
• Not providing adequate patient education about symptoms of hyperglycemia and hypoglycemia

By starting with sitagliptin alone and adding dapagliflozin if needed, you can achieve better glycemic control while maintaining quality of life in this patient with multiple myeloma who cannot tolerate metformin.