How should I adjust therapy for a 70‑year‑old man with type 2 diabetes, hypertension, hyperlipidemia, stage 3 chronic kidney disease, worsening glycemic control, elevated blood pressure, and overweight who is on atenolol, semaglutide (Ozempic), insulin glargine (Lantus), glipizide XL (Glucotrol XL), and losartan‑hydrochlorothiazide?

Comprehensive Medication Adjustment Strategy

This patient requires immediate discontinuation of glipizide (Glucotrol XL), addition of an SGLT2 inhibitor, optimization of blood pressure control, and careful insulin dose reduction to prevent hypoglycemia while addressing worsening glycemic control and cardiovascular-renal protection.

Immediate Medication Changes Required

1. Discontinue Glipizide (Glucotrol XL) Immediately

• Glipizide poses unacceptable hypoglycemia risk in this patient with stage 3 CKD (eGFR 59) and should be stopped immediately 1, 2
• While glipizide is technically the "preferred" sulfonylurea in CKD because it lacks active metabolites, sulfonylureas as a class significantly increase hypoglycemia risk in patients with reduced kidney function 1, 2
• The patient is already on insulin glargine 20 units nightly—adding a sulfonylurea creates dangerous hypoglycemia risk that outweighs any glycemic benefit 2
• Safer alternatives with proven cardiovascular and renal benefits are available and should be prioritized 1, 2

2. Add an SGLT2 Inhibitor as First Priority

• Start dapagliflozin 10 mg daily, empagliflozin 10 mg daily, or canagliflozin 100 mg daily immediately 1, 2
• SGLT2 inhibitors are recommended as first-line therapy for patients with type 2 diabetes and CKD with eGFR ≥20 mL/min/1.73 m², regardless of glycemic control needs 1, 2
• These agents reduce CKD progression by 30% (HR 0.70), cardiovascular death by 22-38%, and heart failure hospitalization by 31-39% 1, 2
• The patient's eGFR of 59 is well above the threshold for initiation, and benefits persist even as eGFR declines 1, 2
• Critical: Reduce insulin glargine dose by 20% (from 20 units to 16 units) when starting the SGLT2 inhibitor to prevent hypoglycemia 2, 3

3. Continue Semaglutide (Ozempic) at Current Dose

• The patient is already on semaglutide 2 mg weekly, which provides excellent cardiovascular and renal protection 1, 4, 5
• Semaglutide reduces major kidney disease events by 24%, cardiovascular death by 29%, and all-cause mortality by 20% in patients with type 2 diabetes and CKD 4
• The combination of semaglutide with an SGLT2 inhibitor provides additive cardiorenal protection 1, 2, 5
• Continue current dose without adjustment 4

4. Optimize Blood Pressure Control

• Current BP of 150/84 mmHg is above target and requires immediate intervention 1
• Target blood pressure should be <130 mmHg systolic (individualized to <130 mmHg if tolerated, but not <120 mmHg) 1
• Switch from atenolol to a cardioselective beta-blocker or discontinue beta-blocker entirely if no compelling indication (no mention of heart failure or coronary disease in this case)
• Optimize RAAS blockade: Increase losartan dose from 50 mg to 100 mg daily 1
• The current losartan-hydrochlorothiazide 50-12.5 provides suboptimal RAAS blockade 1
• Consider switching to losartan 100 mg alone initially, as the patient's eGFR of 59 suggests adequate renal function may allow for more aggressive RAAS blockade without the diuretic 6
• Monitor potassium closely when increasing losartan, especially after adding SGLT2 inhibitor (which reduces hyperkalemia risk) 1

Revised Medication Regimen

New regimen:

• Discontinue: Glucotrol XL 10 mg two tablets daily (stop immediately)
• Discontinue: Atenolol 50 mg twice daily (no clear indication; contributes to suboptimal BP control)
• Reduce: Lantus (insulin glargine) from 20 units to 16 units SQ nightly (20% reduction to prevent hypoglycemia)
• Continue: Ozempic (semaglutide) 2 mg SQ weekly
• Add: Dapagliflozin 10 mg daily, empagliflozin 10 mg daily, OR canagliflozin 100 mg daily 1, 2
• Increase: Losartan from 50 mg to 100 mg daily (discontinue combination product; use losartan alone) 1
• Monitor: Consider restarting low-dose hydrochlorothiazide (12.5 mg) only if BP remains >130 mmHg after 2-4 weeks on losartan 100 mg 1

Monitoring Plan

Week 1-2 After Changes

• Increase home glucose monitoring to 4 times daily (fasting, pre-lunch, pre-dinner, bedtime) to detect hypoglycemia after stopping glipizide and reducing insulin 2, 3
• Educate patient on hypoglycemia symptoms and treatment (glucose tablets, juice) 1
• Monitor blood pressure at home twice daily 1

Week 2-4 After Changes

• Check basic metabolic panel (potassium, creatinine, eGFR) at 2 weeks to assess for hyperkalemia or acute eGFR decline with SGLT2 inhibitor initiation 2
• Recheck blood pressure in office at 2-4 weeks 1
• If BP remains >130 mmHg systolic, add hydrochlorothiazide 12.5 mg daily 1

Month 3 Follow-up

• Recheck HbA1c (expect 0.5-1.0% reduction from SGLT2 inhibitor and stopping glipizide without hypoglycemia) 1, 2
• Recheck eGFR and urine albumin-to-creatinine ratio 1
• Reassess insulin glargine dose based on glucose patterns—may need further titration upward if glycemic control inadequate 7
• If HbA1c remains >8% despite these changes, consider increasing insulin glargine by 2-4 units 7

Every 3-6 Months Ongoing

• Monitor HbA1c, eGFR, and urine albumin-to-creatinine ratio 1, 2
• Continue SGLT2 inhibitor until eGFR falls below 20 mL/min/1.73 m² or dialysis initiation 2

Critical Pitfalls to Avoid

Do Not Continue Glipizide

• Never rationalize continuing sulfonylureas in CKD because "glipizide is the preferred one"—this misses the point that ALL sulfonylureas carry unacceptable hypoglycemia risk when safer alternatives exist 1, 2
• The patient is already on insulin, making sulfonylurea use particularly dangerous 1, 2

Do Not Delay SGLT2 Inhibitor Initiation

• Do not wait to add an SGLT2 inhibitor "until glycemic control worsens further"—the primary indication is cardiorenal protection, not glucose lowering 1, 2
• The patient's eGFR of 59, hypertension, and cardiovascular risk factors make SGLT2 inhibitor use a Class I recommendation regardless of HbA1c 1

Do Not Forget Insulin Dose Reduction

• Always reduce insulin dose by 20% when adding any glucose-lowering agent to prevent hypoglycemia 2, 3
• Failure to reduce insulin when stopping glipizide and adding SGLT2 inhibitor will result in severe hypoglycemia 2, 3

Do Not Ignore Blood Pressure

• BP of 150/84 mmHg significantly increases cardiovascular and renal risk—this requires immediate attention, not "monitoring" 1
• Atenolol is a poor choice for hypertension in diabetes (non-cardioselective, may mask hypoglycemia) and should be discontinued unless there is a compelling indication 1

Do Not Stop SGLT2 Inhibitor When Glucose-Lowering Effect Diminishes

• As eGFR declines below 45 mL/min/1.73 m², the glucose-lowering effect of SGLT2 inhibitors diminishes, but cardiorenal protection persists down to eGFR 20 2
• Continue SGLT2 inhibitor for cardiorenal protection even if HbA1c rises 2

Expected Outcomes

Glycemic Control

• Expect HbA1c reduction of 0.5-1.0% from SGLT2 inhibitor addition 1, 2
• Stopping glipizide may transiently worsen glycemic control, but this is offset by SGLT2 inhibitor and elimination of hypoglycemia risk 1, 2
• If HbA1c remains >8% at 3 months, titrate insulin glargine upward by 2-4 units every 3-7 days until fasting glucose 80-130 mg/dL 7

Cardiovascular and Renal Protection

• SGLT2 inhibitor reduces cardiovascular death by 22-38%, heart failure hospitalization by 31-39%, and CKD progression by 30% 1, 2
• Semaglutide reduces major kidney disease events by 24%, cardiovascular death by 29%, and all-cause mortality by 20% 4
• Combined therapy provides additive benefits 5

Blood Pressure

• Target BP <130/80 mmHg should be achievable with losartan 100 mg ± hydrochlorothiazide 12.5 mg 1
• SGLT2 inhibitors provide modest BP reduction (2-4 mmHg systolic) as an additional benefit 1, 2