What is the best course of action for managing a male patient with diabetes, hypertension, hyperlipidemia, and chronic kidney disease, who has an increasing HbA1c level, impaired renal function, and is currently on Farxiga (dapagliflozin), Lantus (insulin glargine), and rosuvastatin, but was intolerant to Mounjaro (tirzepatide)?

Management of Worsening Glycemic Control in a Patient with Diabetes and CKD

Immediate Treatment Intensification Required

This patient requires aggressive insulin titration and addition of a GLP-1 receptor agonist, while continuing Farxiga for renal protection and addressing the severe hypertriglyceridemia with fenofibrate or high-dose omega-3 fatty acids. 1

Critical Assessment of Current Situation

Glycemic Control Crisis

• HbA1c has risen from 9.3% to 10.3% despite current therapy, indicating treatment failure requiring immediate intensification 1
• With eGFR 59 mL/min (CKD stage 3a), target HbA1c should be 7.0-8.0% rather than <7.0%, as patients with CKD stages 3-5 on insulin experienced 1.5-3 fold increases in severe hypoglycemia with intensive therapy targeting HbA1c <7.0% in ADVANCE, ACCORD, and VADT trials 2, 1
• The current Lantus dose of 72 units may represent overbasalization without adequate prandial coverage, as doses exceeding 0.5 units/kg/day suggest the need for prandial insulin addition rather than further basal increases 1

Renal Function Considerations

• eGFR 59 mL/min allows continued use of Farxiga, which should be maintained for cardiovascular and renal protection independent of glycemic effects 3
• Patients with eGFR <60 mL/min are at increased risk for volume depletion with SGLT2 inhibitors, requiring monitoring for signs of hypotension and acute kidney injury 3

Severe Hypertriglyceridemia

• Triglycerides of 593 mg/dL represent severe hypertriglyceridemia requiring immediate treatment to prevent acute pancreatitis (threshold typically >500 mg/dL)
• This level of hypertriglyceridemia may contribute to insulin resistance and worsen glycemic control
• Rosuvastatin 10 mg is inadequate; this patient needs fibrate therapy or high-dose omega-3 fatty acids (icosapent ethyl 4g daily or omega-3-acid ethyl esters) added to statin therapy

Step-by-Step Treatment Plan

Step 1: Optimize Basal Insulin Dosing

• Increase Lantus from 72 units to 80-84 units (increase by 4 units every 3 days) until fasting glucose reaches 100-130 mg/dL 1
• Monitor for hypoglycemia and reduce dose by 10-20% if episodes occur 1
• Maximum effective basal insulin dose is approximately 0.5 units/kg/day; beyond this, adding prandial insulin is more effective than further basal increases 1

Step 2: Add GLP-1 Receptor Agonist (Since Mounjaro Not Tolerated)

• Initiate a different GLP-1 receptor agonist such as semaglutide (Ozempic) 0.25 mg weekly, or dulaglutide (Trulicity) 0.75 mg weekly, as these provide HbA1c reduction of 0.6-0.8% with cardiovascular benefits and minimal hypoglycemia risk 1, 4, 5
• GLP-1 receptor agonists are superior to insulin intensification alone for patients with HbA1c >9%, with studies showing equal or greater HbA1c reduction compared to insulin glargine, plus weight loss rather than weight gain 5
• If the patient cannot tolerate any GLP-1 receptor agonist due to gastrointestinal side effects, proceed directly to prandial insulin addition 1

Step 3: Consider Prandial Insulin Addition if Needed

• If HbA1c remains >8.0% after 3 months despite optimized basal insulin and GLP-1 receptor agonist, add rapid-acting insulin before the largest meal, starting with 4 units or 10% of basal dose 1, 6
• Titrate prandial insulin by 1-2 units or 10-15% twice weekly based on post-prandial glucose readings 1
• Studies show that intensification from basal insulin to basal-bolus therapy reduces HbA1c by an additional 0.94-1.29% over 12-24 weeks 7

Step 4: Address Severe Hypertriglyceridemia

• Add fenofibrate 48-145 mg daily (dose-adjust for eGFR 59) OR icosapent ethyl 2g twice daily to rosuvastatin
• Fenofibrate requires dose reduction with eGFR 30-59 mL/min; use 48 mg daily in this patient
• Severe hypertriglyceridemia worsens insulin resistance and must be treated aggressively
• Increase rosuvastatin from 10 mg to 20-40 mg daily to achieve better LDL control, as LDL 72 mg/dL is acceptable but could be lower given cardiovascular risk

Step 5: Continue Farxiga with Monitoring

• Maintain Farxiga 10 mg daily for cardiovascular and renal protection, as SGLT2 inhibitors reduce cardiovascular death and heart failure hospitalization independent of glycemic control 1
• Monitor for volume depletion, urinary tract infections, and genital mycotic infections 3
• Educate patient on sick day management: temporarily discontinue Farxiga during acute illness with vomiting, diarrhea, or decreased oral intake to prevent ketoacidosis and volume depletion 2, 3

Critical Monitoring Timeline

At 1 Month

• Assess fasting glucose, post-prandial glucose, and hypoglycemia frequency
• Check for GLP-1 receptor agonist tolerability (nausea, vomiting)
• Monitor triglycerides to assess response to fibrate/omega-3 therapy
• Assess volume status and check basic metabolic panel for acute kidney injury

At 3 Months

• Recheck HbA1c (target 7.0-8.0% for this patient with CKD stage 3a) 2, 1
• Recheck lipid panel to ensure triglycerides <500 mg/dL
• Reassess eGFR and adjust medications if renal function declines
• If HbA1c remains >8.0%, proceed with prandial insulin addition 1, 4

At 6 Months

• Recheck HbA1c to confirm sustained glycemic improvement
• Continue monitoring renal function every 3-6 months

Important Caveats and Pitfalls

Hypoglycemia Risk

• The combination of insulin and SGLT2 inhibitor increases hypoglycemia risk, requiring patient education on recognition and treatment 3
• Patients with CKD have impaired insulin clearance and defective counterregulatory responses, increasing hypoglycemia risk 2
• If hypoglycemia occurs, reduce insulin dose by 10-20% immediately 1

Sick Day Management

• Educate patient to temporarily stop Farxiga during acute illness with vomiting, diarrhea, decreased oral intake, or fever to prevent diabetic ketoacidosis and acute kidney injury 2, 3
• Patient should increase fluid intake and monitor blood glucose every 4-6 hours during illness 2
• Resume Farxiga within 24-48 hours of eating and drinking normally 2

Volume Depletion Risk

• Patients with eGFR <60 mL/min on SGLT2 inhibitors are at increased risk for volume depletion, hypotension, and acute kidney injury 3
• Monitor for lightheadedness, dizziness, decreased urine output, and orthostatic hypotension 2, 3

Avoiding Overbasalization

• Do not increase basal insulin beyond approximately 0.5 units/kg/day without adding prandial insulin, as this leads to increased hypoglycemia without proportional HbA1c benefit 1
• The pattern of elevated HbA1c with high basal insulin dose suggests inadequate prandial coverage 1

Why Not Other Options?

• Sulfonylureas should NOT be added due to high hypoglycemia risk when combined with insulin in patients with CKD 2, 8
• DPP-4 inhibitors are less effective when added to a regimen already containing a GLP-1 receptor agonist 4
• Thiazolidinediones (pioglitazone) are not recommended due to fluid retention risk, which is particularly problematic in patients with CKD and hypertension 4

Expected Outcomes

• With aggressive insulin titration plus GLP-1 receptor agonist addition, expect HbA1c reduction of 1.5-2.5% over 3-6 months, bringing HbA1c from 10.3% to target range of 7.5-8.0% 1, 5
• GLP-1 receptor agonists provide weight loss of 2-4 kg rather than weight gain associated with insulin intensification alone 5
• Triglyceride reduction of 30-50% expected with fenofibrate or omega-3 fatty acid therapy