What is the appropriate initial prescription for a patient with hypertension or diabetes?

Initial Prescription for Hypertension in Diabetes

For patients with diabetes and blood pressure ≥160/100 mmHg, immediately initiate dual therapy with an ACE inhibitor (such as lisinopril 10 mg daily) combined with either a thiazide-like diuretic (chlorthalidone or indapamide preferred) or a dihydropyridine calcium channel blocker, alongside lifestyle modifications. 1, 2

Blood Pressure Thresholds and Treatment Intensity

Severe Hypertension (≥160/100 mmHg)

• Start with two antihypertensive medications immediately to achieve adequate blood pressure control more rapidly than monotherapy 1, 2
• Single-pill combination therapy may improve medication adherence 1

Moderate Hypertension (140-159/90-99 mmHg)

• Begin with single-agent pharmacologic therapy in addition to lifestyle modifications 1
• Titrate promptly if blood pressure targets are not achieved 1

Mild Elevation (130-139/80-89 mmHg)

• Initiate lifestyle therapy alone for maximum 3 months, then add pharmacologic treatment if targets remain unmet 1

Preferred Drug Classes and Combinations

First-Line Agents

ACE inhibitors are the preferred initial choice for most patients with diabetes and hypertension due to proven cardiovascular benefits and renoprotective effects 1, 2

• Lisinopril starting dose: 10 mg once daily for hypertension, adjustable to 20-40 mg daily based on response 3
• If ACE inhibitor is not tolerated (typically due to cough), substitute with an ARB 1

Evidence-Based Combination Regimens

The following two-drug combinations are recommended 1, 2:

• ACE inhibitor + thiazide-like diuretic (chlorthalidone or indapamide preferred over hydrochlorothiazide) 1
• ACE inhibitor + dihydropyridine calcium channel blocker 1
• ARB + thiazide-like diuretic 1, 2
• ARB + dihydropyridine calcium channel blocker 1, 2

Special Considerations for Albuminuria

For patients with urine albumin-to-creatinine ratio ≥30 mg/g, ACE inhibitor or ARB is mandatory as first-line therapy to reduce progressive kidney disease risk 1

• With UACR ≥300 mg/g: ACE inhibitor or ARB strongly recommended 1
• With UACR 30-299 mg/g: ACE inhibitor or ARB suggested 1
• Without albuminuria: ACE inhibitors/ARBs show no superior cardioprotection compared to thiazide-like diuretics or dihydropyridine calcium channel blockers 1

Critical Contraindications

NEVER combine an ACE inhibitor with an ARB - this combination significantly increases risks of hyperkalemia, syncope, and acute kidney injury without additional benefit 1, 2

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

Blood Pressure Targets

Target blood pressure: <130/80 mmHg for most patients with diabetes 1

• Less stringent target (<140/90 mmHg) may be appropriate for elderly patients or those with severe coronary heart disease 1
• Most patients require 3-4 antihypertensive medications to achieve target 1

Mandatory Lifestyle Interventions

Initiate concurrently with pharmacologic therapy 1, 2:

• Weight loss if overweight or obese 1
• DASH-style dietary pattern with reduced sodium and increased potassium intake 1
• Moderation of alcohol intake 1
• Increased physical activity 1

Monitoring Requirements

Laboratory Monitoring

Monitor serum creatinine/eGFR and potassium levels 1, 2:

• At baseline before initiating ACE inhibitor, ARB, or diuretic 1, 2
• At least annually during treatment 1, 2
• More frequently if eGFR <60 mL/min/1.73 m² 1

Clinical Monitoring

• Assess for orthostatic hypotension at each visit to screen for autonomic neuropathy 1, 2
• Blood pressure should be measured at every routine diabetes visit 1

Dose Adjustment Considerations

Consider reducing ACE inhibitor/ARB dose or discontinuation if 1:

• Creatinine rises >30% from baseline 1
• Hyperkalemia develops 1
• Most common avoidable cause: diuretic-induced volume depletion 1

Common Pitfalls to Avoid

Inadequate Treatment Intensity

• 48% of patients with chronic kidney disease receive only one antihypertensive drug - this is grossly inadequate 1
• Only 11% of patients with reduced kidney function achieve BP <130/85 mmHg 1
• Do not hesitate to escalate to triple or quadruple therapy when needed 1

Beta-Blocker Misuse

• Beta-blockers are NOT first-line agents for uncomplicated hypertension in diabetes 1
• Reserve for specific indications: prior MI, active angina, or heart failure with reduced ejection fraction 1
• Beta-blockers may worsen insulin sensitivity and increase triglycerides 4

Resistant Hypertension Management

If blood pressure remains ≥140/90 mmHg on three drugs (including a diuretic), add a mineralocorticoid receptor antagonist 1

Renal Dosing Adjustments

For patients with creatinine clearance 10-30 mL/min 3:

• Reduce initial lisinopril dose to 5 mg daily (half the usual dose) 3
• Titrate as tolerated to maximum 40 mg daily 3

For hemodialysis or creatinine clearance <10 mL/min 3:

• Initial lisinopril dose: 2.5 mg once daily 3