What additional medication can be considered for a patient with type 2 diabetes mellitus and persistent hyperglycemia, currently on glipizide and insulin glargine, with a history of metformin intolerance and prior discontinuation of Ozempic and Jardiance?

Additional Medication for Persistent Hyperglycemia

Given your glucose readings ranging from 130s to 300s mg/dL despite glipizide and insulin glargine, you should add an SGLT2 inhibitor (such as restarting Jardiance/empagliflozin) as your next medication, while simultaneously reducing or discontinuing glipizide to minimize hypoglycemia risk. 1

Rationale for SGLT2 Inhibitor Addition

The 2018 ADA/EASD consensus guidelines prioritize SGLT2 inhibitors after metformin for patients who cannot tolerate metformin, which applies directly to your situation 1. Key advantages include:

• Weight neutrality or modest weight loss (addressing your concern about dietary control and overeating) 1
• Low hypoglycemia risk when combined with insulin, unlike sulfonylureas 1
• Complementary mechanism to insulin that reduces total insulin requirements 2
• Cardiovascular and renal benefits in patients with diabetes 2
• Your GFR of 95 mL/min makes you an ideal candidate for SGLT2 inhibitor therapy 1

Why Jardiance Was Likely Discontinued and Why to Reconsider

Since you previously used Jardiance but discontinued it for "unclear reasons," and your current renal function is excellent (GFR 95 mL/min), there is no contraindication to restarting it 1. The most common reasons for discontinuation are genital mycotic infections (4-5% in males) or urinary tract infections, both of which are manageable 3.

Critical Medication Adjustment Required

You must reduce or discontinue glipizide when intensifying your diabetes regimen 4, 2. Here's why:

• Sulfonylureas like glipizide significantly increase hypoglycemia risk when combined with insulin 1, 2
• Guidelines explicitly recommend discontinuing sulfonylureas when initiating or intensifying insulin therapy 4, 2
• Your glucose variability (130s to 300s) suggests unpredictable insulin sensitivity, making hypoglycemia from glipizide particularly dangerous 1

Alternative Option: DPP-4 Inhibitor

If SGLT2 inhibitors are not tolerated or if genital infections recur, a DPP-4 inhibitor (such as sitagliptin or linagliptin) would be the next best choice 1. These agents:

• Are weight neutral 1
• Have very low hypoglycemia risk 1
• Are well-tolerated with minimal side effects 1
• Can be safely combined with insulin 1

However, DPP-4 inhibitors provide less glucose-lowering efficacy than SGLT2 inhibitors and lack the cardiovascular benefits 1.

Why NOT to Consider Other Options

GLP-1 Receptor Agonists (like Ozempic)

You already experienced pancreatitis with Ozempic, making all GLP-1 receptor agonists contraindicated 1. This is an absolute contraindication that cannot be overcome.

Pioglitazone (TZD)

While pioglitazone could be considered 5, 6, 7, it causes:

• Significant weight gain (counterproductive to your dietary goals) 1
• Fluid retention (concerning with your asthma history) 6
• Increased fracture risk 1
• Less favorable profile than SGLT2 inhibitors 1

Insulin Intensification Consideration

Your glucose readings reaching 300s mg/dL indicate you may also need insulin glargine dose optimization 4, 2. The standard approach:

• Increase basal insulin by 2-4 units every 3-7 days until fasting glucose consistently reaches 80-130 mg/dL 4, 2
• Monitor for hypoglycemia, especially after reducing/stopping glipizide 4
• Consider adding prandial insulin (4 units at largest meal) if fasting glucose is controlled but post-meal readings remain elevated 2

Common Pitfalls to Avoid

• Do not continue glipizide while intensifying insulin therapy - this dramatically increases hypoglycemia risk 4, 2
• Do not add multiple oral agents simultaneously - start with one medication and assess response over 3 months 1
• Do not ignore the "unclear reasons" for Jardiance discontinuation - clarify this history before restarting, but if it was simply cost or access, proceed with restarting 1
• Do not consider any GLP-1 receptor agonist given your pancreatitis history 1

Practical Implementation

Start empagliflozin 10 mg daily (can increase to 25 mg if tolerated after 4 weeks) 8, discontinue glipizide immediately 4, and continue insulin glargine with dose titration as described above 4, 2. Monitor for genital mycotic infections and maintain excellent hydration 3.