How to manage a patient with T2DM, HTN, and hypercholesterolemia who has worsening proteinuria, suboptimal glycemic control, and elevated LDL levels?

Management of T2DM with Worsening Proteinuria, Suboptimal Glycemic Control, and Elevated LDL

This patient requires immediate intensification of therapy with an SGLT2 inhibitor continuation, addition of a GLP-1 receptor agonist for glycemic control and cardiovascular protection, statin dose optimization or addition of ezetimibe for LDL reduction, and consideration of a nonsteroidal mineralocorticoid receptor antagonist given the worsening albuminuria despite RAS blockade. 1

Glycemic Control Strategy

Target HbA1c and Current Status:

• Current HbA1c of 57 mmol/mol (7.4%) is close to but above the target of <55 mmol/mol (<7.2%), representing improved but still suboptimal control 1
• The patient is already on triple therapy (Galvumet 50/1000mg BD [sitagliptin/metformin], empagliflozin 25mg OD), yet glycemic targets remain unmet 1

Medication Optimization:

• Continue empagliflozin 25mg daily as SGLT2 inhibitors are first-line therapy for T2DM with CKD, providing kidney and heart protection independent of glucose lowering 1
• Empagliflozin should be continued until dialysis or transplantation is initiated, even as eGFR declines, as it can be initiated when eGFR ≥20 ml/min per 1.73 m² 1
• Add a GLP-1 receptor agonist (preferably semaglutide or dulaglutide) as the next step to achieve glycemic targets, given proven cardiovascular benefits and additional glucose-lowering efficacy 1
• GLP-1 RAs are the preferred additional glucose-lowering drug when SGLT2i and metformin are insufficient to meet glycemic targets 1
• Continue metformin (component of Galvumet) as it remains appropriate with eGFR >90 ml/min per 1.73 m² 1
• Consider discontinuing or reducing sitagliptin (DPP-4 inhibitor component of Galvumet) when adding a GLP-1 RA, as combining these agents provides minimal additional benefit and is generally not recommended 1

Addressing Medication Non-Adherence:

• The patient reports occasionally forgetting post-meal medications, which likely refers to the Galvumet BD dosing 1
• Simplifying the regimen by switching to once-daily GLP-1 RA formulations (e.g., semaglutide, dulaglutide) may improve adherence 1
• Provide structured diabetes self-management education focusing on medication timing and the importance of consistent dosing 1

Diabetic Nephropathy Management

Worsening Proteinuria Assessment:

• ACR has increased from 6.4 to 11.8 mg/mmol, and microalbumin has risen from 7 to 46 mg/L, indicating progressive diabetic kidney disease 1
• Despite being on lisinopril 10mg (ACE inhibitor), proteinuria is worsening, suggesting inadequate RAS blockade or need for additional nephroprotective therapy 1

Intensification of Kidney Protection:

• Optimize RAS inhibition by increasing lisinopril dose (typical target doses are 20-40mg daily for diabetic nephropathy) if blood pressure tolerates, as ACE inhibitors/ARBs are first-line therapy for hypertension when albuminuria is present 1
• Add a nonsteroidal mineralocorticoid receptor antagonist (finerenone) given persistent albuminuria >30 mg/g (>3 mg/mmol) despite first-line therapy 1
• Finerenone is currently the only nonsteroidal MRA with proven clinical kidney and cardiovascular benefits in patients with T2DM and CKD with albuminuria 1
• This addition is specifically indicated for patients with T2DM and high residual risk of kidney disease progression, evidenced by persistent albuminuria despite SGLT2i and RAS blockade 1
• Monitor potassium levels closely when adding finerenone, ensuring normal potassium before initiation 1

Blood Pressure Optimization:

• Current blood pressure control appears suboptimal based on worsening proteinuria 1
• Target systolic blood pressure to 130 mmHg and, if well tolerated, <130 mmHg but not <120 mmHg 1
• Diastolic blood pressure target <80 mmHg but not <70 mmHg 1
• The patient is already on furosemide 5mg BD; consider adding a dihydropyridine calcium channel blocker if additional blood pressure lowering is needed after optimizing lisinopril dose 1

Lipid Management

Current Lipid Status:

• LDL 2.5 mmol/L with target <1.8 mmol/L indicates inadequate control despite atorvastatin 80mg nocte 1
• This patient has T2DM with diabetic nephropathy (CKD), placing them at very high cardiovascular risk 1

Lipid-Lowering Intensification:

• For patients with T2DM at very high CV risk, an LDL-C target of <1.4 mmol/L (<55 mg/dL) and LDL-C reduction of at least 50% is recommended 1
• Since the patient is already on maximum-dose atorvastatin (80mg), add ezetimibe 10mg daily as the next step 1
• Ezetimibe is indicated when statin monotherapy fails to achieve LDL targets and provides additional 15-20% LDL reduction 2
• If LDL remains above target after adding ezetimibe, consider adding a PCSK9 inhibitor or icosapent ethyl based on ASCVD risk 1
• Continue statin therapy as it is recommended for all patients with T1DM or T2DM and CKD, and statins are safe in patients with kidney disease 1

Monitoring for Statin-Related Effects:

• The patient has elevated ferritin (553, normal 20-450) and slightly elevated eosinophils (0.6), which should be monitored but are not contraindications to statin therapy 2
• Continue monitoring liver function tests and creatine kinase periodically, though current LFTs are normal 2

Lifestyle Modifications

Weight Management:

• Weight management should be a central focus, with an individualized weight loss goal of at least 5% body weight 1
• Substantial weight loss (>10%) increases the chance of diabetes remission and improves cardiovascular outcomes 1
• The addition of a GLP-1 RA with high weight loss efficacy can provide 10-15% weight loss or more 1

Physical Activity:

• Target at least 150 minutes per week of moderate-intensity physical activity 1
• Break up sedentary time with activity breaks (e.g., 5-minute activity break every hour) 1
• Address the patient's complaint of fatigue worsening with cold weather, which may improve with better glycemic control and weight loss 1

Dietary Modifications:

• Develop a personalized food plan through medical nutrition therapy, as there is no single dietary pattern recommended for all individuals with T2DM 1
• Focus on dietary patterns that support weight loss, glycemic control, and cardiovascular health 1

Addressing Fatigue

Potential Contributors:

• Suboptimal diabetes control (HbA1c 57) may contribute to fatigue 1
• Thyroid function is normal, ruling out hypothyroidism 1
• Hemoglobin is normal, ruling out anemia 1
• Consider that worsening kidney function or cardiovascular disease may contribute to fatigue 1
• Reassess fatigue after optimizing glycemic control and addressing cardiovascular risk factors 1

Monitoring and Follow-Up

Regular Risk Factor Reassessment (Every 3-6 Months):

• HbA1c monitoring every 3 months until target achieved, then every 3-6 months 1
• Lipid panel every 3-6 months after intensification until target achieved 1
• Urine albumin-to-creatinine ratio every 3-6 months to monitor proteinuria progression 1
• eGFR and electrolytes every 3-6 months, with more frequent monitoring after adding finerenone 1
• Blood pressure monitoring at each visit 1

Self-Monitoring:

• Emphasize self-monitoring behaviors including blood glucose monitoring, weight measurement, and physical activity tracking 1
• Review self-monitoring data at each visit to adjust treatment and reinforce behavioral goals 1

Common Pitfalls to Avoid

• Do not delay adding GLP-1 RA when SGLT2i and metformin are insufficient to achieve glycemic targets, as this patient has been on triple therapy without reaching goal 1
• Do not withhold statins due to kidney disease; they are safe and beneficial in CKD 1
• Do not overlook medication adherence issues; simplifying the regimen and providing education are critical 1
• Do not accept persistent albuminuria without escalating therapy; add finerenone when albuminuria persists despite SGLT2i and RAS blockade 1
• Do not use hypocaloric diets if the patient develops decompensated cirrhosis (not currently present), though this is not a concern in this case 1