How should I manage a 60‑year‑old woman with type 2 diabetes mellitus, hemoglobin A1c 8.3 %, stage 3a chronic kidney disease (eGFR 77 mL/min, serum creatinine 0.87 mg/dL), severe hypertriglyceridemia (triglycerides 506 mg/dL) and intermittent dizziness who is taking metformin 500 mg twice daily, Jardiance (empagliflozin) 10 mg daily, Januvia (sitagliptin) 100 mg daily, and glipizide 5 mg twice daily?

Immediate Medication Adjustments Required

Stop glipizide immediately and reduce metformin to 1000 mg daily maximum, while continuing Jardiance 10 mg and Januvia 100 mg; add a high-intensity statin and prescription omega-3 fatty acids for the severe hypertriglyceridemia, and investigate the dizziness as it may represent hypoglycemia from the sulfonylurea. 1, 2

Critical Safety Issues to Address First

1. Glipizide Must Be Discontinued

• Glipizide poses unacceptable hypoglycemia risk at eGFR 77 mL/min/1.73 m² (CKD stage 2) and is likely causing the reported dizziness episodes. 2, 3
• Sulfonylureas increase severe hypoglycemia risk 5-fold in patients with declining renal function, and this risk increases progressively as eGFR declines. 4, 5
• The combination of glipizide with Januvia (sitagliptin) increases hypoglycemia risk by approximately 50% compared to sulfonylurea alone. 6
• Metformin is safer than sulfonylureas at this level of kidney function, with lower all-cause mortality (HR 0.48), fewer cardiovascular events (HR 0.67), and dramatically fewer major hypoglycemic episodes (HR 0.14). 3

2. Metformin Dose Reduction Required

• At eGFR 77 mL/min/1.73 m² (CKD stage 2), current metformin 1000 mg daily is acceptable, but the dose must not exceed 1000 mg daily. 1, 2
• FDA guidance states metformin should not be initiated when eGFR <45 mL/min/1.73 m², and benefits/risks should be reassessed when eGFR falls to <45 mL/min/1.73 m². 1
• Monitor eGFR every 3-6 months; if it falls below 45 mL/min/1.73 m², reduce metformin to maximum 1000 mg daily. 2
• Metformin is contraindicated when eGFR <30 mL/min/1.73 m². 1, 2

3. SGLT2 Inhibitor Optimization

• Continue Jardiance (empagliflozin) 10 mg daily—this is the single most important medication for this patient. 1, 2
• At eGFR 77 mL/min/1.73 m², Jardiance provides critical cardiorenal protection independent of glucose-lowering effects, reducing CKD progression, cardiovascular death, and heart failure hospitalization. 1, 2, 7, 8
• The glucose-lowering effect diminishes at eGFR <45 mL/min/1.73 m², but cardiovascular and renal benefits persist down to eGFR 20 mL/min/1.73 m². 2, 9
• Never discontinue Jardiance based on reduced glycemic effect—the primary benefit at this stage is cardiorenal protection, not A1c reduction. 2

4. DPP-4 Inhibitor Considerations

• Continue Januvia (sitagliptin) 100 mg daily without dose adjustment at eGFR 77 mL/min/1.73 m². 2, 6
• Sitagliptin requires dose reduction only when eGFR falls below 45 mL/min/1.73 m²: 50 mg daily for eGFR 30-44, and 25 mg daily for eGFR <30. 2, 6
• Sitagliptin has neutral cardiovascular safety (TECOS trial) and minimal hypoglycemia risk when not combined with sulfonylureas. 6
• Once glipizide is stopped, the hypoglycemia risk from Januvia becomes minimal. 6

Severe Hypertriglyceridemia Management

Immediate Lipid Therapy Required

• Triglycerides 506 mg/dL require urgent treatment to reduce both ASCVD risk and pancreatitis risk. 1
• Start high-intensity statin therapy immediately (atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily). 1
• Add prescription omega-3 fatty acids (icosapent ethyl 2 grams twice daily or EPA/DHA 4 grams daily) to reduce triglycerides and cardiovascular events. 1
• Monitor liver enzymes (ALT) within 12 weeks of statin initiation. 1

Lifestyle and Medication Synergy

• Jardiance will help reduce triglycerides through weight loss and improved insulin sensitivity. 7, 8
• Emphasize carbohydrate restriction, as high triglycerides in diabetes often reflect poor glycemic control and excess carbohydrate intake. 1
• Recheck lipid panel in 8-12 weeks after statin and omega-3 initiation. 1

Investigating the Dizziness

Most Likely Cause: Hypoglycemia from Glipizide

• The combination of glipizide 5 mg BID with Januvia in the setting of CKD stage 2 creates high hypoglycemia risk. 2, 6, 3
• Obtain continuous glucose monitoring (CGM) or have patient check fingerstick glucose during dizzy episodes to confirm hypoglycemia. 4
• Once glipizide is stopped, dizziness should resolve if hypoglycemia is the cause. 3

Alternative Causes to Consider

• Volume depletion from Jardiance (SGLT2 inhibitor) combined with any diuretic use—assess orthostatic vital signs. 2
• Cardiovascular causes (arrhythmia, orthostatic hypotension)—check blood pressure sitting and standing, obtain ECG. 1
• If dizziness persists after stopping glipizide, pursue cardiovascular evaluation. 1

Glycemic Control Strategy After Glipizide Discontinuation

Expected A1c After Medication Adjustment

• Current A1c 8.3% with four agents including a sulfonylurea suggests the regimen is not optimally effective. 2
• After stopping glipizide, A1c may rise 0.5-1.0%, but this is acceptable given the unacceptable hypoglycemia risk. 2, 3
• The combination of metformin 1000 mg daily, Jardiance 10 mg, and Januvia 100 mg should maintain A1c in the 7.5-8.5% range. 2, 10

If Additional Glucose Lowering Needed

• Add a GLP-1 receptor agonist (semaglutide 0.5-1 mg weekly or liraglutide 1.2-1.8 mg daily) if A1c remains >8% after 3 months. 1, 2, 10
• GLP-1 RAs provide additional A1c reduction of 1.0-1.5%, promote weight loss (which will help triglycerides), and have proven cardiovascular benefits. 1, 10
• GLP-1 RAs have minimal hypoglycemia risk and can be safely used at eGFR 77 mL/min/1.73 m². 2
• Do not add another sulfonylurea or increase insulin—these increase hypoglycemia risk without cardiorenal benefits. 2, 3

Monitoring Plan

Short-Term (Next 2-4 Weeks)

• Check fingerstick glucose or obtain CGM to document resolution of hypoglycemia after stopping glipizide. 4
• Assess dizziness resolution. 3
• Monitor for volume depletion symptoms (lightheadedness, orthostatic hypotension) from Jardiance. 2

Medium-Term (3 Months)

• Recheck A1c to assess glycemic control after glipizide discontinuation. 2
• Recheck lipid panel to assess response to statin and omega-3 therapy. 1
• Recheck eGFR and urine albumin-to-creatinine ratio to monitor CKD progression. 1, 2
• Recheck ALT to monitor for statin hepatotoxicity. 1

Long-Term (Every 3-6 Months)

• Monitor eGFR and urine albumin-to-creatinine ratio every 3-6 months. 1, 2
• If eGFR falls below 45 mL/min/1.73 m², reduce metformin dose and reassess sitagliptin dose. 1, 2
• Monitor A1c every 3-6 months; add GLP-1 RA if A1c >8% persists. 2

Common Pitfalls to Avoid

• Never continue sulfonylureas in patients with CKD and recurrent hypoglycemia—the mortality and morbidity risks far outweigh any glycemic benefit. 2, 3
• Never stop Jardiance based on A1c alone—its primary value in CKD is cardiorenal protection, not glucose lowering. 2, 8
• Never ignore severe hypertriglyceridemia in diabetes—it increases both ASCVD and pancreatitis risk and requires aggressive treatment. 1
• Never assume dizziness in a diabetic patient on sulfonylureas is "just vertigo"—always rule out hypoglycemia first. 3
• Never exceed metformin 1000 mg daily when eGFR is between 30-44 mL/min/1.73 m²—this patient is approaching that threshold. 1, 2