What additional medication can be considered for a patient with a history of pancreatitis due to Victoza (liraglutide), uncontrolled diabetes, hyperglycemia, and currently on Jardiance (empagliflozin), metformin, and Semglee (insulin glargine)?

Increase Insulin Dose and Consider Adding a DPP-4 Inhibitor or Sulfonylurea

Given this patient's history of pancreatitis from Victoza (a GLP-1 RA), the safest approach is to optimize her current insulin therapy first by increasing Semglee to 15-20 units at bedtime, then consider adding a DPP-4 inhibitor (such as sitagliptin) or a sulfonylurea (such as glimepiride) if additional glycemic control is needed after 2-3 months. 1, 2

Why GLP-1 RAs Are Contraindicated in This Patient

• GLP-1 receptor agonists should be avoided in patients with a history of pancreatitis, as concerns regarding increased pancreatitis risk remain unresolved, and these agents should be discontinued if pancreatitis is suspected 1, 2
• The American Diabetes Association explicitly recommends avoiding GLP-1 RAs in patients with a history of pancreatitis due to potential increased risk 2
• DPP-4 inhibitors have also been linked to pancreatitis and should be discontinued if pancreatitis develops, though they may be used with caution in this population 1
• Both GLP-1 RAs and DPP-4 inhibitors have been rarely reported to be associated with pancreatitis and should be used with extreme caution in patients with prior pancreatitis 1

Immediate Treatment Algorithm

Step 1: Optimize Insulin Therapy (First Priority)

• Increase Semglee (insulin glargine) from 10 units to 15-20 units at bedtime, as individuals with pancreatogenic diabetes may require early insulin initiation and optimization to achieve glycemic goals 1
• Insulin is the preferred agent during and after pancreatitis as it does not stimulate pancreatic secretion and effectively manages hyperglycemia 2
• Titrate insulin glargine by 2-4 units every 3-7 days based on fasting blood glucose, targeting fasting glucose 80-130 mg/dL 1
• Multiple daily injection regimens are typically required, with half of daily requirements given as prandial coverage and half as once-daily long-acting insulin 2

Step 2: Consider Adding Oral Agents After Insulin Optimization (2-3 Months)

If blood sugars remain elevated after optimizing basal insulin:

• DPP-4 inhibitors (sitagliptin 100 mg daily) can be considered as second-line therapy if pancreatitis and elevated lipase are absent, though they should be used with caution given the pancreatitis history 1
• Sulfonylureas (glimepiride 1-2 mg daily) are an alternative option, as they have not been associated with pancreatitis risk and can improve glycemic variability 1
• The addition of a DPP-4 inhibitor to a sulfonylurea may help improve glycemic variability and attainment of glycemic goals in individuals with a history of pancreatitis 1

Step 3: Continue Current SGLT2 Inhibitor and Metformin

• Continue Jardiance (empagliflozin) 25 mg daily, as SGLT2 inhibitors have demonstrated cardiovascular and kidney benefits, though they are associated with increased DKA risk 1
• Continue metformin 500 mg TID (total 1500 mg daily), as it remains first-line therapy and should be used with caution if eGFR is <45 mL/min/1.73 m² 1
• Consider increasing metformin to 2000 mg daily (667 mg TID) if tolerated and renal function permits, as this is the typical target dose 1

Critical Monitoring and Safety Considerations

• Monitor blood glucose hourly until stable, then every 2-4 hours during any acute illness or medication changes 2
• Assess for ketones at home if using SGLT2 inhibitors, as these agents are associated with increased DKA risk 1
• Do not abruptly discontinue insulin without transitioning to alternative therapy, as rebound hyperglycemia can occur 2
• Transition from insulin to oral agents only after complete resolution of any pancreatic symptoms and careful consideration of medication-related pancreatitis risk 2

Why This A1C/Glucose Discordance Matters

• The A1C of 6.9% does not match blood sugars running 250 mg/dL, suggesting either recent worsening of control, significant glycemic variability, or laboratory error 1
• This discordance indicates the patient likely needs more aggressive insulin titration rather than adding new oral agents immediately 1
• Target A1C should be <7% for most adults with diabetes, with individualization based on comorbidities 1

Common Pitfalls to Avoid

• Never continue GLP-1 agonists or DPP-4 inhibitors in patients with active or recent pancreatitis despite their glycemic efficacy 2
• Do not delay insulin optimization while attempting to add oral agents—insulin should be the foundation of therapy in this patient 1, 2
• Avoid pioglitazone (TZD) due to concerns of increased bladder cancer risk and weight gain, though it has modest cardiovascular benefit 1
• Do not use niacin or fibrates primarily for glucose control, as these are lipid-lowering agents without proven glycemic benefit in this context 1, 3

Alternative Considerations If Above Approach Fails

• Consider insulin pump therapy or automated insulin delivery systems when appropriate for patients requiring intensive insulin management 1
• Pramlintide (amylin agonist) is typically reserved for patients on intensive insulin therapy and decreases post-prandial glucose by inhibiting glucagon secretion 1
• Alpha-glucosidase inhibitors (acarbose) retard gut carbohydrate absorption but have gastrointestinal side effects and modest efficacy 1