What is the best course of treatment for a patient with type 2 diabetes (T2D), hypertension (HTN), bradycardia, impaired renal function, and an enlarged prostate, who is experiencing fatigue and excessive sleepiness, with lab results showing hyperglycemia (A1C 8.9), elevated creatinine (1.60), and elevated B-type natriuretic peptide (BNP) levels, and is currently taking Lantus (insulin glargine) 60 units, Janumet (sitagliptin and metformin), Losartan (losartan potassium) 100mg, Rosuvastatin (rosuvastatin calcium), Tamsulosin (tamsulosin hydrochloride), and Metoprolol (metoprolol tartrate) 12.5mg?

Management of Fatigue and Sleepiness in a Complex Diabetic Patient with CKD

This patient's fatigue and sleepiness are likely multifactorial, but the immediate priority is addressing metoprolol-induced bradycardia, optimizing diabetes management with SGLT2 inhibitor therapy, correcting B12 deficiency, and urgently evaluating for heart failure and prostate cancer.

Immediate Medication Adjustments

Discontinue or Reduce Metoprolol

• Stop metoprolol 12.5mg immediately as bradycardia combined with beta-blocker therapy is a primary contributor to fatigue and excessive sleepiness 1, 2
• The elevated BNP (139 pg/mL, normal 0-100) suggests early heart failure, but beta-blockers can worsen bradycardia and fatigue in this context 3
• Losartan 100mg provides adequate cardiovascular and renal protection without contributing to bradycardia 4, 5

Add SGLT2 Inhibitor Immediately

• Initiate empagliflozin 10mg, dapagliflozin 10mg, or canagliflozin 100mg daily given GFR 44 mL/min/1.73 m² (CKD Stage 3a) 1, 2
• SGLT2 inhibitors provide kidney protection, cardiovascular benefits, and reduce heart failure hospitalizations independent of glucose-lowering effects, with benefits persisting down to eGFR 20 mL/min/1.73 m² 1, 2
• Reduce Lantus dose by 20% (from 60 to 48 units) when starting SGLT2 inhibitor to prevent hypoglycemia 1, 2

Optimize Metformin Dosing

• Reduce Janumet to maximum metformin 1000mg daily given GFR 44 mL/min/1.73 m² 1, 2
• Metformin dose must be reduced when eGFR is 30-44 mL/min/1.73 m², and discontinued if eGFR falls below 30 mL/min/1.73 m² 1, 2
• Continue sitagliptin component as DPP-4 inhibitors are safe in CKD 6

Address Specific Deficiencies

Correct B12 Deficiency

• B12 level of 158 pg/mL is deficient (normal >200 pg/mL) and directly causes fatigue, weakness, and cognitive dysfunction 6
• Initiate cyanocobalamin 1000 mcg intramuscularly weekly for 4-8 weeks, then monthly maintenance or oral cyanocobalamin 1000-2000 mcg daily 6
• Metformin therapy commonly causes B12 deficiency, making supplementation essential 6

Evaluate Elevated BNP

• BNP 139 pg/mL suggests early heart failure or volume overload, which contributes significantly to fatigue 3
• Order echocardiogram to assess left ventricular function and evaluate for heart failure with preserved or reduced ejection fraction 6, 3
• Consider adding loop diuretic if echocardiogram confirms heart failure or volume overload 6, 2

Critical Urologic Evaluation

Urgent Prostate Cancer Screening

• The patient's refusal to see urology for enlarging prostate is unacceptable given cancer risk 7
• Elevated alkaline phosphatase (202 U/L) may indicate bone metastases from prostate cancer, which would explain fatigue 7
• Order PSA level immediately and strongly counsel patient on cancer screening necessity 7
• Untreated prostate cancer with potential metastases dramatically impacts mortality and quality of life 7

Blood Pressure and Renal Protection

Optimize RAS Blockade

• Continue losartan 100mg as it provides renal protection in diabetic nephropathy with elevated creatinine and proteinuria 4, 5
• Losartan reduces progression of nephropathy as measured by doubling of serum creatinine or end-stage renal disease 4, 5
• Target blood pressure <130/80 mmHg in patients with diabetes and CKD 6, 2

Monitor Renal Function Closely

• Check serum creatinine, potassium, and eGFR within 2-4 weeks after adding SGLT2 inhibitor 7, 2
• Monitor eGFR and urine albumin-to-creatinine ratio every 3-6 months to track CKD progression 1, 2
• Continue losartan unless creatinine rises >30% within 4 weeks, which would warrant evaluation for acute kidney injury 2

Glycemic Management Strategy

Reassess A1C Target

• Current A1C 8.9% requires intensification, but target should be <7.5-8.0% given CKD Stage 3a and hypoglycemia risk 6, 2
• Adding SGLT2 inhibitor will improve glycemic control while providing cardiorenal protection 1, 2
• Monitor HbA1c every 3 months until target achieved, then every 6 months 2

Insulin Adjustment

• Consider simplifying from Lantus to once-daily basal insulin (glargine, detemir, or degludec) if patient is on complex regimen 1
• Patients with CKD Stage 3-4 may require 25% or more insulin dose reduction due to decreased clearance 1
• Increased hypoglycemia risk in CKD requires careful monitoring 1, 2

Monitoring and Follow-Up Plan

Short-Term (2-4 Weeks)

• Recheck creatinine, potassium, and eGFR after SGLT2 inhibitor initiation 7, 2
• Assess symptomatic improvement in fatigue after metoprolol discontinuation 1
• Obtain PSA level and schedule urology consultation 7
• Order echocardiogram to evaluate BNP elevation 3

Medium-Term (3 Months)

• Recheck HbA1c to assess glycemic response to SGLT2 inhibitor 2
• Recheck B12 level after supplementation 6
• Monitor blood pressure to ensure <130/80 mmHg target 6, 2
• Assess urine albumin-to-creatinine ratio 2

Long-Term (Every 3-6 Months)

• Monitor eGFR, creatinine, and potassium 2
• Continue SGLT2 inhibitor until dialysis or transplantation, even as eGFR declines 1, 2
• Reassess cardiovascular risk factors and consider statin intensification 7, 2

Common Pitfalls to Avoid

• Never discontinue SGLT2 inhibitor based solely on reduced glucose-lowering effect at lower eGFR—the primary benefit is cardiorenal protection, not glycemic control 1, 2
• Do not add sulfonylureas given significantly increased hypoglycemia risk in CKD and availability of safer alternatives 1, 2
• Do not ignore the prostate cancer screening refusal—untreated cancer dramatically impacts mortality and quality of life 7
• Do not continue metoprolol in a bradycardic patient with fatigue—the beta-blocker is likely contributing significantly to symptoms 1, 3
• Do not delay B12 supplementation—deficiency directly causes the patient's presenting symptoms 6