What is the recommended management plan for a patient with diabetes (Diabetes Mellitus), hypertension, and a history of cardiovascular disease or kidney disease, including target blood glucose and blood pressure levels and pharmacologic therapy?

Management of Diabetes with Hypertension and Cardiovascular/Kidney Disease

Blood Pressure Target and Initiation Threshold

For patients with diabetes, hypertension, and cardiovascular or kidney disease, target blood pressure is <130/80 mmHg, and pharmacologic therapy should be initiated at blood pressure ≥130/80 mmHg alongside lifestyle modifications. 1

• Blood pressure should be measured at every routine diabetes visit 1
• Confirmed office-based readings ≥130/80 mmHg qualify for immediate pharmacologic intervention 1

Pharmacologic Therapy Algorithm

For Blood Pressure 130-159/80-99 mmHg:

Start with single-agent therapy using an ACE inhibitor or ARB as first-line, particularly given the presence of cardiovascular or kidney disease. 1

• ACE inhibitors or ARBs are strongly recommended for patients with urine albumin-to-creatinine ratio ≥300 mg/g creatinine 1
• ACE inhibitors or ARBs are suggested for patients with coronary artery disease or urine albumin-to-creatinine ratio 30-299 mg/g creatinine 1
• If one class is not tolerated, substitute the other 1
• Titrate to maximum tolerated dose indicated for blood pressure treatment 1

For Blood Pressure ≥160/100 mmHg:

Immediately initiate two antihypertensive medications from different drug classes: an ACE inhibitor (or ARB) combined with either a thiazide-like diuretic or a dihydropyridine calcium channel blocker. 1, 2

• Prompt dual therapy achieves adequate blood pressure control more effectively than sequential monotherapy 1, 2
• Preferred thiazide-like diuretics are long-acting agents proven to reduce cardiovascular events: chlorthalidone or indapamide 1

Appropriate Two-Drug Combinations:

• ACE inhibitor + thiazide-like diuretic 1, 2
• ACE inhibitor + dihydropyridine calcium channel blocker 1, 2
• ARB + thiazide-like diuretic 1, 2
• ARB + dihydropyridine calcium channel blocker 1, 2

Critical Contraindications:

Never combine ACE inhibitors with ARBs, as this increases risk of hyperkalemia, syncope, and acute kidney injury without additional benefit. 1, 2

• Do not combine ACE inhibitors or ARBs with direct renin inhibitors 1

Escalation for Inadequate Control

Multiple-drug therapy is generally required to achieve the <130/80 mmHg target. 1

• If blood pressure remains uncontrolled on two agents, add a third drug from the preferred classes (ACE inhibitor/ARB, thiazide-like diuretic, dihydropyridine calcium channel blocker) 1
• Beta-blockers are indicated specifically for prior myocardial infarction, active angina, or heart failure with reduced ejection fraction, but not as routine blood pressure-lowering agents otherwise 1

Resistant Hypertension (≥140/90 mmHg on Three Drugs):

Before diagnosing resistant hypertension, exclude medication nonadherence, white coat hypertension, and secondary hypertension. 1

• Address barriers to medication adherence including cost and side effects 1
• Consider adding a mineralocorticoid receptor antagonist (spironolactone or eplerenone) for patients not meeting targets on three classes including a diuretic 1
• Monitor serum creatinine and potassium closely when adding mineralocorticoid receptor antagonists to ACE inhibitor/ARB regimens due to hyperkalemia risk 1
• Refer to hypertension specialist if targets remain unmet 1

Mandatory Lifestyle Interventions

Lifestyle modifications must be initiated concurrently with pharmacologic therapy, not sequentially. 1

• Weight loss through caloric restriction if overweight or obese 1
• DASH-style eating pattern: 8-10 servings fruits/vegetables daily, 2-3 servings low-fat dairy daily 1
• Sodium restriction to <2,300 mg/day with increased potassium intake 1
• Alcohol moderation: ≤2 servings/day for men, ≤1 serving/day for women 1
• Minimum 150 minutes/week moderate-intensity aerobic physical activity 1

Glycemic Control Considerations

Strongly consider SGLT2 inhibitors (such as empagliflozin) for patients with diabetes and established cardiovascular disease due to proven cardiovascular mortality benefit. 3

• SGLT2 inhibitors and GLP-1 receptor agonists provide additional blood pressure reduction and cardiovascular protection beyond glycemic control 4

Monitoring Requirements

Monitor serum creatinine/eGFR and potassium at baseline, within 7-14 days after initiating or changing dose of ACE inhibitor, ARB, or diuretic, then at least annually. 1, 3

• Continue ACE inhibitor or ARB therapy even as eGFR declines to <30 mL/min/1.73 m² for cardiovascular benefit, unless contraindicated 1
• Assess for orthostatic hypotension at each visit by measuring orthostatic blood pressure 1, 3
• Blood pressure should be measured at every routine diabetes visit 1

Common Pitfalls to Avoid

• Do not delay pharmacologic therapy for a trial of lifestyle modification alone when blood pressure is ≥130/80 mmHg 1
• Do not use monotherapy when blood pressure is ≥160/100 mmHg; dual therapy is required 1, 2
• Do not combine ACE inhibitors with ARBs despite both being renin-angiotensin system blockers 1, 2
• Do not withhold ACE inhibitors/ARBs as kidney function declines unless specific contraindications develop 1
• Do not use short-acting thiazides (hydrochlorothiazide); prefer chlorthalidone or indapamide for cardiovascular event reduction 1