What is the management approach for a 35-year-old female with uncontrolled diabetes mellitus on Lisinopril (Zestril) (20 mg), presenting with hypertension?

From the Guidelines

I strongly recommend increasing the lisinopril dose to 40 mg daily and adding a second antihypertensive medication, such as amlodipine 5 mg daily, to better control this patient's blood pressure, as the current blood pressure is above the target of <130/80 mmHg recommended for diabetic patients 1. The patient's uncontrolled diabetes likely contributes to her hypertension through mechanisms including increased arterial stiffness, endothelial dysfunction, and enhanced sodium retention.

Key Considerations

• ACE inhibitors like lisinopril are first-line agents for diabetic patients with hypertension due to their renoprotective effects, but monotherapy is often insufficient 1.
• When titrating lisinopril, monitor renal function and potassium levels within 1-2 weeks of dose adjustment.
• Additionally, addressing the uncontrolled diabetes is crucial through lifestyle modifications (reduced sodium intake, regular exercise, weight management if applicable) and optimizing diabetes medications.
• The patient should be advised to monitor home blood pressure readings and return for follow-up in 2-4 weeks to assess the effectiveness of these interventions.

Lifestyle Interventions

• Lifestyle intervention consists of weight loss if overweight or obese; a Dietary Approaches to Stop Hypertension–style dietary pattern including reducing sodium and increasing potassium intake; moderation of alcohol intake; and increased physical activity 1.
• Decreasing sodium intake to no more than 1500 mg/d may improve blood pressure in certain circumstances, but restriction to this level for all patients with diabetes is not recommended 1.

Pharmacologic Interventions

• Patients with confirmed office-based blood pressure ≥140/90 mm Hg should, in addition to lifestyle therapy, have prompt initiation and timely titration of pharmacologic therapy to achieve blood pressure goals 1.
• Multiple-drug therapy (including a thiazide diuretic and ACE inhibitor/ARB, at maximal doses) is generally required to achieve blood pressure targets 1.

From the FDA Drug Label

1. 2 Heart Failure In two placebo controlled, 12-week clinical studies compared the addition of lisinopril up to 20 mg daily to digitalis and diuretics alone. The combination of lisinopril, digitalis and diuretics reduced the following signs and symptoms of heart failure: edema, rales, paroxysmal nocturnal dyspnea and jugular venous distention In one of the studies, the combination of lisinopril, digitalis and diuretics reduced orthopnea, presence of third heart sound and the number of patients classified as NYHA Class III and IV; and improved exercise tolerance.

The patient is already on Lisinopril (20 mg), which is the maximum dose used in the heart failure studies.

• The patient has uncontrolled diabetes mellitus and hypertension.
• The drug label does not provide specific guidance on managing hypertension in the context of uncontrolled diabetes mellitus.
• However, it does mention that lisinopril can be used to reduce blood pressure. The management approach for this patient would be to monitor and adjust the current lisinopril dose, if necessary, to control blood pressure, while also addressing the uncontrolled diabetes mellitus through other means, such as adjusting diabetes medications or lifestyle modifications 2.

From the Research

Management Approach

The management approach for a 35-year-old female with uncontrolled diabetes mellitus on Lisinopril (Zestril) (20 mg), presenting with hypertension, involves a combination of lifestyle modifications and pharmacological interventions.

• Dietary and behavioral lifestyle modifications should be an integral part of any management regimen, including:
  • Weight reduction
  • Low sodium diet
  • Exercise
  • Moderate alcohol intake
  • Smoking cessation 3
• Effective control of blood pressure to target levels is more important than the drug(s) used, with a target blood pressure of 130/80 mmHg 3
• Combination drug therapy is often needed to achieve target blood pressure, with options including:
  • Low-dose thiazide diuretics
  • Angiotensin-converting enzyme inhibitors (such as Lisinopril)
  • Angiotensin II receptor blockers
  • Calcium channel blockers
  • β-blockers 3

Pharmacological Interventions

Lisinopril, an angiotensin-converting enzyme inhibitor, is effective in lowering blood pressure in patients with hypertension, including those with diabetes mellitus 4, 5.

• Lisinopril has been shown to be renoprotective in patients with diabetes mellitus, reducing the progression of nephropathy and slowing the progression of retinopathy 5
• The drug has a favorable tolerability profile, with a low risk of hypoglycemia and no adverse effects on glycaemic control or lipid profiles 5
• The antihypertensive effect of Lisinopril has been demonstrated in several studies, with a significant reduction in systolic and diastolic blood pressure observed in patients with hypertension 4, 6

Specific Considerations

In patients with impaired renal function, Lisinopril has been shown to be effective and safe, with a low risk of adverse effects 7.

• The dosage of Lisinopril may need to be adjusted in patients with severe renal impairment, due to the risk of drug accumulation 7
• In patients with diabetes mellitus, Lisinopril may be used as a first-line agent for reducing blood pressure and preventing or attenuating nephropathy, with a target blood pressure of 130/80 mmHg 3, 5