What is the best add-on medication for a 63-year-old female patient with poorly controlled diabetes (A1C of 11.0), who is currently on Lantus (insulin glargine) 75 units PM and sliding scale Humalog (insulin lispro) 8-10 units with meals, Janumet (sitagliptin and metformin) and Farxiga (dapagliflozin), and weighs 219lb?

Best Add-On Medication for Poorly Controlled Type 2 Diabetes

For a 63-year-old female with an A1C of 11.0% on Lantus, sliding scale Humalog, Janumet, and Farxiga, the best add-on therapy is a GLP-1 receptor agonist such as liraglutide or semaglutide. 1

Current Regimen Analysis

• The patient is already on multiple medications including:
  • Basal insulin (Lantus 75 units PM) 1
  • Prandial insulin (Humalog 8-10 units with meals) 1
  • SGLT2 inhibitor (Farxiga/dapagliflozin) 1
  • DPP-4 inhibitor + metformin combination (Janumet) 1
• Despite this regimen, the A1C remains significantly elevated at 11.0%, indicating poor glycemic control requiring treatment intensification 1

Recommendation Algorithm

Step 1: Evaluate Current Regimen Effectiveness

• A1C of 11.0% is ≥1.5% above target, indicating need for more potent glucose-lowering therapy 1
• Current combination of basal insulin, prandial insulin, SGLT2 inhibitor, and DPP-4 inhibitor/metformin is not achieving glycemic goals 1

Step 2: Consider Best Add-On Option

• GLP-1 receptor agonist is the optimal choice because:
  • The American Diabetes Association recommends GLP-1 RAs over intensifying insulin when possible 1
  • GLP-1 RAs provide significant A1C reduction (0.7-1.5%) in patients with elevated baseline A1C 2
  • They offer weight benefits in this patient who weighs 219 lb 1
  • They have complementary mechanisms to the current regimen 1

Step 3: Implementation Considerations

• Discontinue the DPP-4 inhibitor component of Janumet (sitagliptin) while maintaining metformin when adding a GLP-1 RA, as combining DPP-4 inhibitors with GLP-1 RAs provides minimal additional benefit 1
• Consider once-weekly formulations (e.g., semaglutide) for better adherence 1
• Start with lower doses and titrate up to minimize gastrointestinal side effects 2

Evidence Supporting GLP-1 RA Addition

• In clinical trials, liraglutide 1.8mg added to existing therapy showed a 1.5% reduction in A1C compared to 0.9% with sitagliptin 2
• GLP-1 RAs are preferred to insulin intensification according to current guidelines 1
• They provide glucose-dependent insulin secretion, reducing hypoglycemia risk compared to insulin intensification 1
• They offer additional benefits of weight loss and potential cardiovascular protection 1

Alternative Options (If GLP-1 RA Not Suitable)

• Insulin intensification: Convert to basal-bolus regimen with proper dose adjustment 3
  • Increase basal insulin by 2-4 units every 3-7 days until fasting glucose reaches target 3
  • Adjust prandial insulin doses based on carbohydrate intake and pre-meal glucose levels 3
• Consider twice-daily premixed insulin if adherence to multiple daily injections is challenging 3

Potential Pitfalls and Caveats

• Adding GLP-1 RA may cause initial gastrointestinal side effects (nausea, vomiting, diarrhea) 2
• Monitor for hypoglycemia when combining with insulin; insulin dose reduction may be necessary 3
• Ensure patient doesn't have personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 before starting GLP-1 RA 1
• Cost and insurance coverage may be barriers to GLP-1 RA therapy 1

Monitoring Recommendations

• Check A1C every 3 months until target is achieved 1
• Monitor for hypoglycemia, especially with insulin and GLP-1 RA combination 3
• Assess weight changes and adjust therapy as needed 1
• Evaluate for adherence to medication regimen and lifestyle modifications 1