What is the best course of treatment for a male patient with type 2 diabetes, currently on Novolog (aspart) 30 units subcutaneously (SQ) twice a day and metformin 1000 mg twice a day, with an improved Hemoglobin A1c (HbA1c) level of 9.2% from 10.1% three months ago and impaired renal function, as indicated by an estimated Glomerular Filtration Rate (eGFR) of 71?

Treatment Intensification for Uncontrolled Type 2 Diabetes with Renal Impairment

Add an SGLT2 inhibitor with proven cardiovascular and kidney benefit to the current regimen of metformin and insulin aspart, while reducing the metformin dose to 1000 mg daily given the eGFR of 71 mL/min/1.73 m². 1

Immediate Medication Adjustments

Metformin Dose Reduction

• Reduce metformin from 2000 mg/day to 1000 mg/day given the eGFR of 71 mL/min/1.73 m² (Stage 2 CKD), as the 2022 ADA/KDIGO consensus recommends dose reduction when eGFR is between 45-60 mL/min/1.73 m², and conservative dosing is prudent at eGFR 60-75 mL/min/1.73 m² 1
• Continue metformin as the foundation of therapy unless contraindicated (eGFR <30 mL/min/1.73 m²), as it provides established efficacy, cardiovascular benefits, and low cost 1
• Monitor vitamin B12 levels periodically, as metformin use is associated with vitamin B12 deficiency and worsening neuropathy symptoms 1, 2

Add SGLT2 Inhibitor

• Initiate an SGLT2 inhibitor (canagliflozin, dapagliflozin, or empagliflozin) with proven kidney and cardiovascular benefit, as the ADA/KDIGO consensus strongly recommends SGLT2 inhibitors for patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² 1
• SGLT2 inhibitors provide HbA1c reduction of 0.6-0.8% when added to existing therapy, with preserved kidney and cardiovascular benefits even as glucose-lowering efficacy diminishes at lower eGFR 1
• Dapagliflozin 10 mg daily or canagliflozin 100-300 mg daily are appropriate choices at this eGFR level 1
• Once initiated, the SGLT2 inhibitor can be continued at lower levels of eGFR for organ protection 1

Insulin Optimization

• Aggressively titrate the insulin aspart dose by increasing 4 units every 3 days until fasting glucose reaches target (<130 mg/dL), as the current 30 units twice daily (60 units total) may be insufficient 3
• The current insulin regimen addresses prandial coverage but may need intensification given the HbA1c of 9.2% 3
• Consider that insulin aspart at mealtimes provides superior glycemic control compared to basal insulin alone, with greater HbA1c reduction (-0.41% difference), though at the expense of higher body weight and mild daytime hypoglycemia 4

Alternative Cost-Effective Option if SGLT2 Inhibitor Unavailable

Given the financial constraints mentioned, if SGLT2 inhibitors are not affordable:

• Add a sulfonylurea (glimepiride 1-2 mg daily) as a low-cost second-line agent, which provides HbA1c reduction of approximately 1.0-1.5% 1
• Glimepiride costs approximately $4-15 per month for generic formulations, making it highly cost-effective 1
• Initiate conservatively at 1 mg daily and titrate slowly to avoid hypoglycemia, particularly given the Stage 2 CKD 1
• However, this option sacrifices the cardiovascular and kidney protective benefits of SGLT2 inhibitors, which are critical given the existing renal impairment 1

Critical Monitoring Requirements

Short-Term Monitoring (First 3 Months)

• Recheck HbA1c after 3 months to assess treatment effectiveness 1, 3
• Monitor eGFR at least every 3-4 months given the baseline impairment and medication adjustments 1
• Assess for SGLT2 inhibitor-related adverse effects: genital mycotic infections (6% incidence), volume depletion, and euglycemic ketoacidosis (rare but serious, especially in insulin-treated patients) 1
• Monitor for hypoglycemia, particularly if sulfonylurea is used instead of SGLT2 inhibitor 1

Long-Term Monitoring

• Obtain eGFR at least annually, or more frequently given the patient's age and existing renal impairment 1, 2
• Monitor vitamin B12 levels periodically on metformin therapy 1, 2
• Check urine albumin-to-creatinine ratio annually to assess for albuminuria progression 5

Expected Outcomes and Further Intensification

Expected HbA1c Reduction

• The addition of an SGLT2 inhibitor should provide an additional 0.6-0.8% HbA1c reduction 1
• Combined with insulin optimization, this should bring HbA1c from 9.2% to approximately 7.5-8.0% within 3 months 3

If Target Not Achieved at 3 Months

• If HbA1c remains >7.5% after 3 months despite optimized therapy, add a GLP-1 receptor agonist (if financially feasible), which provides superior HbA1c reduction (1.0-1.5%) with cardiovascular benefits and weight loss rather than weight gain 1, 3
• GLP-1 receptor agonists (dulaglutide, liraglutide, semaglutide) require no dose adjustment at this eGFR level 1
• If HbA1c remains >7% after 3-6 months on triple therapy, transition to basal-bolus insulin regimen by adding basal insulin (glargine or degludec) to the existing prandial insulin 1, 3

Important Caveats and Pitfalls

SGLT2 Inhibitor Precautions

• Educate the patient to temporarily discontinue the SGLT2 inhibitor during acute illness or stressors to mitigate euglycemic ketoacidosis risk, and maintain at least low-dose insulin during these periods 1
• Counsel on daily hygienic measures to reduce genital mycotic infection risk 1
• Ensure adequate hydration to minimize volume depletion risk 1

Metformin Safety at This eGFR

• While metformin is safe at eGFR 71 mL/min/1.73 m², the dose reduction to 1000 mg/day provides a safety margin as eGFR may fluctuate 1, 2
• Metformin is contraindicated if eGFR falls below 30 mL/min/1.73 m² 1, 2
• Temporarily discontinue metformin during acute illness, dehydration, or if contrast imaging is planned 2

Financial Considerations

• SGLT2 inhibitors cost $257-448 per month, which may be prohibitive given stated financial constraints 1
• If cost is truly prohibitive, the sulfonylurea option provides substantial glycemic benefit at minimal cost ($4-15/month), though without organ protection 1
• Consider patient assistance programs for SGLT2 inhibitors given the critical kidney protective benefits at this stage of CKD 1