What is the best course of action for managing diabetes, hypertension, and hyperlipidemia in a patient with impaired renal function, elevated liver enzymes, and a BMI of 48?

Glycemic Management Optimization

This patient requires immediate intensification of her diabetes regimen by discontinuing glipizide and significantly increasing her Mounjaro dose to 15 mg weekly, with consideration of basal insulin optimization. 1

Current Regimen Assessment

The patient's HbA1c of 10.3% despite quadruple therapy indicates treatment failure requiring urgent intervention. Her current regimen includes:

• Farxiga (dapagliflozin) 10 mg daily - appropriate and should be continued given eGFR of 63 1
• Mounjaro (tirzepatide) 10 mg weekly - underdosed for her degree of hyperglycemia 1
• Lantus 30 units nightly - likely insufficient 1
• Glipizide 10 mg twice daily - should be discontinued 1

Immediate Medication Changes

Discontinue Glipizide

Stop glipizide immediately as sulfonylureas add minimal glycemic benefit when combined with GLP-1 receptor agonists, increase hypoglycemia risk, and promote weight gain—counterproductive in a patient with BMI 48. 1

Escalate Mounjaro Dose

Increase Mounjaro to 15 mg weekly immediately, as the current 10 mg dose is clearly inadequate given the HbA1c of 10.3%. 1 The 2022 Mayo Clinic guidelines recommend GLP-1 receptor agonists be titrated to maximum doses for patients with obesity and poorly controlled diabetes. 1

Optimize Basal Insulin

Increase Lantus by 20% (to approximately 36 units nightly) and implement a systematic titration protocol: increase by 2-4 units every 3 days until fasting glucose reaches 80-130 mg/dL. 1 With HbA1c >10%, initial dual-regimen intensification is appropriate. 1

Continue SGLT2 Inhibitor

Maintain Farxiga 10 mg daily as it provides kidney protection with eGFR of 63 and can be safely continued until eGFR falls below 20. 1, 2 No dose adjustment is needed at this level of renal function. 1, 2

Renal Function Considerations

With eGFR 63, this patient has CKD stage 2-3a. 1

• Metformin is safe at this eGFR level and could be added if not already prescribed, as it can be used down to eGFR 30. 1
• Dapagliflozin requires no dose adjustment and provides cardiovascular and kidney protection. 1, 2
• GLP-1 receptor agonists require no renal dose adjustment and are preferred agents in diabetic kidney disease. 1

Hypertension and Cardiovascular Risk Management

RAS Blockade

Initiate or optimize ACE inhibitor or ARB therapy titrated to maximum tolerated dose, as this patient likely has albuminuria given her diabetes duration and poor control. 1, 3 Monitor serum creatinine and potassium 2-4 weeks after initiation. 1

Blood Pressure Target

Target blood pressure <130/80 mmHg using combination therapy as needed (ACE-I/ARB plus dihydropyridine calcium channel blocker and/or diuretic). 1

Hyperlipidemia Management

Statin Therapy

Initiate high-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) as recommended for all patients with diabetes and CKD. 1 Her ALT of 40 and AST of 35 are within acceptable limits for statin initiation. 4

Additional Lipid Management

Consider ezetimibe or PCSK9 inhibitor if LDL goals are not met with statin monotherapy, particularly given her multiple cardiovascular risk factors. 1

Weight Management Priority

With BMI 48, this patient has severe obesity requiring aggressive intervention. 1

• Mounjaro at maximum dose (15 mg weekly) provides substantial weight loss benefits beyond glycemic control. 1
• Semaglutide 2.4 mg weekly could be considered as an alternative if Mounjaro is insufficient, as it is FDA-approved for weight management in patients with BMI >30. 1
• Discontinuing glipizide removes a weight-promoting medication. 1

Monitoring Plan

Short-term (2-4 weeks)

• Fasting glucose daily for insulin titration 1
• Serum creatinine and potassium if ACE-I/ARB initiated or adjusted 1
• Blood pressure monitoring 1

Medium-term (3 months)

• Repeat HbA1c 1
• Urine albumin-to-creatinine ratio 1, 3
• Lipid panel 1
• Liver enzymes 4

Critical Pitfalls to Avoid

Do not continue ineffective sulfonylurea therapy in patients already on GLP-1 receptor agonists and insulin—this adds hypoglycemia risk without meaningful benefit. 1

Do not withhold SGLT2 inhibitors due to mild-moderate renal impairment; they are kidney-protective and safe until eGFR <20. 1

Do not delay insulin intensification when HbA1c remains >10% despite multiple agents—this represents clear treatment failure requiring immediate action. 1

Do not forget comprehensive cardiovascular risk reduction including RAS blockade, statin therapy, and blood pressure control, as these interventions reduce mortality more than glycemic control alone in patients with diabetic kidney disease. 1