What are the risks of hypotension with terzipitide (glucagon-like peptide-1 (GLP-1) receptor agonist)?

Hypotension Risk with Tirzepatide

Tirzepatide carries minimal risk of hypotension based on its pharmacologic class (GLP-1 receptor agonist), but clinicians must exercise heightened vigilance in patients receiving concurrent heart failure guideline-directed medical therapy (GDMT) or other antihypertensive medications, where significant drug interactions causing symptomatic hypotension have been documented. 1

Direct Blood Pressure Effects

GLP-1 receptor agonists as a class have minimal to no effect on blood pressure in most patients:

• Chronic administration of GLP-1 receptor agonists produces modest systolic blood pressure reductions of approximately 2 mmHg when used for glycemic control 2
• These agents demonstrate a neutral effect on hypotension risk in cardiovascular outcome trials 3
• Patients with systolic blood pressure as low as 95 mmHg were safely enrolled in major trials without excess symptomatic hypotension 3
• The blood pressure lowering effect is not consistently observed across all studies, with some ambulatory blood pressure monitoring trials showing no significant reduction 2

High-Risk Clinical Scenarios

Three specific situations warrant careful monitoring for hypotension:

1. Concurrent Heart Failure GDMT

• Case series documentation shows tirzepatide can cause symptomatic hypotension requiring GDMT modification in patients receiving angiotensin receptor neprilysin inhibitors, beta blockers, mineralocorticoid receptor antagonists, and SGLT2 inhibitors 1
• The mechanism involves tirzepatide's direct vasodilation, natriuresis, reduction in extracellular volume, and weight loss effects 1
• Two of three reported cases developed acute kidney injury from volume depletion 1
• This drug interaction is not currently indexed in major drug interaction databases 1

2. Volume-Depleted States

• SGLT2 inhibitors cause hypotension through intravascular volume depletion, and tirzepatide may compound this effect when used in combination 3
• Patients requiring loop diuretics are at particular risk and may need diuretic dose reduction 1

3. Perioperative Period

• Delayed gastric emptying from GLP-1 receptor activation increases pulmonary aspiration risk during anesthesia 4
• Careful timing of tirzepatide administration relative to surgical procedures is necessary 4

Monitoring Strategy

Implement the following surveillance protocol:

• Monitor vital signs and volume status closely after tirzepatide initiation, particularly in the first 2-4 weeks 1
• Assess blood pressure at every clinical visit, or at minimum every 6 months 3
• In patients on GDMT for heart failure, consider preemptive reduction of diuretic doses or vasodilator therapy 1
• Watch for orthostatic symptoms, dizziness, or signs of volume depletion 1

Cardiovascular Side Effect Profile

Beyond hypotension, tirzepatide causes increased heart rate:

• Elevated heart rate is a recognized class effect of GLP-1 receptor agonists 3, 4
• If cardiac arrhythmia or symptomatic tachycardia develops, monitoring and consideration of beta blockers may be necessary 4
• This contrasts with SGLT2 inhibitors, which lower blood pressure without increasing heart rate 5

Critical Pitfall to Avoid

The most important clinical trap is failing to anticipate the drug interaction between tirzepatide and heart failure medications. Since this interaction is not indexed in standard drug databases, clinicians must proactively adjust GDMT regimens rather than reactively responding to symptomatic hypotension or acute kidney injury 1. Consider empiric reduction of loop diuretic doses by 25-50% when initiating tirzepatide in patients on complex heart failure regimens.