How to manage uncontrolled type 2 diabetes mellitus in a patient with CKD stage 3 and multiple comorbidities?

Optimizing Uncontrolled Type 2 Diabetes in CKD Stage 3

Your patient is already on Ozempic (GLP-1 RA), Jardiance (SGLT2i), and insulin (Humalog + Toujeo), which represents appropriate triple therapy per guidelines, so the primary issue is likely inadequate insulin dosing rather than missing medication classes—you need to systematically uptitrate her basal and bolus insulin while ensuring her SGLT2i and GLP-1 RA are at maximum tolerated doses. 1

Immediate Medication Review and Optimization

Step 1: Verify SGLT2i and GLP-1 RA Dosing

• Confirm Jardiance (empagliflozin) is at 25 mg daily, as this is the maximum dose that provides optimal glycemic, cardiovascular, and renal protection in CKD stage 3 (eGFR ≥30 mL/min/1.73 m²). 1, 2
• Verify Ozempic (semaglutide) is at maximum dose of 2 mg weekly, as the GLP-1 RA should be at full therapeutic dose before aggressive insulin titration. 1
• Both medications are appropriate for CKD stage 3 and should be continued even if eGFR drops below 30 mL/min/1.73 m² as long as dialysis is not imminent. 1

Step 2: Assess and Optimize Basal Insulin

• Toujeo Max U-300 should be uptitrated by 10-20% (or 2-4 units if dose <20 units) every 3 days until fasting glucose reaches 80-130 mg/dL, as inadequate basal insulin is the most common cause of uncontrolled diabetes in patients already on combination therapy. 1
• Monitor for hypoglycemia, particularly given her CKD stage 3, which increases insulin sensitivity and prolongs insulin half-life. 1
• Target fasting glucose of 80-130 mg/dL before addressing postprandial control. 1

Step 3: Optimize Bolus Insulin

• Once basal insulin is optimized, uptitrate Humalog using a carbohydrate-to-insulin ratio starting at 1:15 and adjusting based on 2-hour postprandial glucose readings. 1
• Add or increase correction factor dosing for pre-meal glucose >130 mg/dL, starting with 1 unit per 50 mg/dL above target and adjusting based on response. 1
• Consider switching to a fixed-ratio combination (insulin degludec/liraglutide) if adherence to multiple daily injections is a barrier, though this patient is already on separate GLP-1 RA. 1

Critical Medication Interactions and Adjustments

Medications Affecting Glycemic Control

• Carvedilol (beta-blocker) may mask hypoglycemia symptoms and slightly worsen insulin resistance—monitor glucose more frequently during insulin titration. 1
• Atorvastatin is appropriate and should be continued for cardiovascular risk reduction in diabetic CKD. 1
• Aripiprazole may worsen hyperglycemia—consider discussing with prescribing psychiatrist if glycemic control remains poor despite insulin optimization, though psychiatric stability takes priority. 1

Metformin Dosing Verification

• With CKD stage 3, metformin dose should not exceed 1000 mg daily if eGFR is 30-44 mL/min/1.73 m², and should be discontinued if eGFR drops below 30 mL/min/1.73 m². 1
• I do not see metformin listed in her current medications—if her eGFR is ≥30 mL/min/1.73 m², adding metformin 500-1000 mg daily would provide additional glycemic benefit as first-line therapy per ADA/KDIGO guidelines. 1
• Monitor eGFR every 3-6 months once below 60 mL/min/1.73 m² and hold metformin during acute illness or procedures requiring contrast. 1

Monitoring and Follow-Up Strategy

Immediate (First 2-4 Weeks)

• Obtain continuous glucose monitoring (CGM) or increase self-monitoring to 4-6 times daily (fasting, pre-meals, 2-hour post-meals, bedtime) to identify patterns and guide insulin titration. 1
• Check eGFR, potassium, and HbA1c to establish baseline kidney function and ensure no acute kidney injury that would require medication adjustment. 1, 3
• Review time-in-range (70-180 mg/dL) as primary metric rather than relying solely on HbA1c, which may be falsely low due to her anemia. 1

Short-Term (1-3 Months)

• Uptitrate insulin every 3-7 days based on glucose patterns until 70% of readings are in target range (70-180 mg/dL). 1
• Reassess HbA1c at 3 months with target of <7% for most patients, though <8% may be appropriate given her multiple comorbidities and hypoglycemia risk. 1
• Monitor for SGLT2i-related adverse effects including genital mycotic infections, volume depletion (especially with concurrent diuretics), and euglycemic DKA. 1, 2

Long-Term (Every 3-6 Months)

• Monitor eGFR and urine albumin-to-creatinine ratio every 3-6 months to assess CKD progression and ensure continued appropriateness of current medications. 1, 4
• Check vitamin B12 annually if metformin is added, as long-term use (>4 years) increases deficiency risk. 4
• Assess for diabetic complications including retinopathy progression (she already has proliferative retinopathy), neuropathy worsening, and cardiovascular events. 1

Common Pitfalls to Avoid

• Do not discontinue SGLT2i or GLP-1 RA to "simplify" the regimen—these provide critical cardiorenal protection independent of glycemic effects and should be continued even if HbA1c reaches target. 1
• Do not undertitrate insulin due to fear of hypoglycemia—with proper monitoring and patient education, aggressive insulin titration is safe and necessary in uncontrolled diabetes. 1
• Do not add sulfonylureas—they increase hypoglycemia risk in CKD and provide inferior cardiorenal outcomes compared to current regimen. 1
• Do not stop metformin prematurely—it is safe down to eGFR 30 mL/min/1.73 m² with dose reduction and provides foundational glycemic control. 1

If Glycemic Control Remains Poor After Optimization

• Consider insulin pump therapy or closed-loop system if multiple daily injections with optimized dosing fail to achieve targets. 1
• Evaluate for medication non-adherence using pharmacy refill data and direct patient discussion—her complex regimen (20+ medications) significantly increases non-adherence risk. 5
• Assess for unrecognized hypoglycemia causing rebound hyperglycemia, particularly given her history of hypoglycemia unawareness risk factors (autonomic neuropathy, beta-blocker use). 1
• Rule out secondary causes of hyperglycemia including uncontrolled hypothyroidism (she's on levothyroxine—verify TSH is at target), occult infection, or steroid use. 4