Tirzepatide Dramatically Worsened POTS Symptoms in a Young Woman Using It for Weight Loss | Research

The takeaway

Tirzepatide caused a 20-30 bpm heart rate increase and recurrence of POTS symptoms in a young woman — far exceeding the small heart rate effect typically seen with GLP-1 drugs.

20-30 bpm increase
Tirzepatide caused a heart rate increase 7-10x greater than the typical ~3 bpm effect of GLP-1 drugs in a patient with postural orthostatic tachycardia syndrome

What the researchers found

A 28-year-old woman with obesity and POTS (postural orthostatic tachycardia syndrome) experienced significant worsening of her condition while using tirzepatide for weight loss. Despite having successfully controlled her POTS through exercise training (reducing heart rates to normal values), tirzepatide caused a 20-30 beats/min increase in both supine and standing heart rates — far exceeding the typical ~3 bpm increase seen with GLP-1 drugs. She also experienced recurrence of orthostatic intolerance symptoms.

This magnitude of heart rate increase with tirzepatide in a POTS patient has not been previously reported.

Why it matters

As tirzepatide and other GLP-1/GIP peptide drugs are prescribed to millions of patients for weight loss, clinicians need to understand their effects in patients with coexisting cardiovascular conditions. This case reveals that POTS patients — who already struggle with heart rate dysregulation — may be particularly vulnerable to the heart rate-increasing effects of these peptide drugs, potentially undoing the benefits of established POTS treatments like exercise training.

The numbers in context

20-30 bpm heart rate increase · vs ~3 bpm typical GLP-1 effect · 28-year-old patient · POTS recurrence · Exercise benefits reversed

How the study worked

Single case report from JACC Case Reports. A 28-year-old woman with obesity and POTS was monitored during exercise-based POTS treatment and subsequent tirzepatide therapy. Supine and standing heart rates were measured before and during tirzepatide use. Orthostatic intolerance symptoms were tracked clinically.

Who was studied

Single 28-year-old woman with obesity and postural orthostatic tachycardia syndrome (POTS)

What this study cannot tell us

This is a single case report (n=1) and cannot establish causation or estimate the prevalence of this adverse effect in POTS patients. The patient had pre-existing POTS, so the results may not apply to patients without autonomic disorders. It is unclear whether the effect is specific to tirzepatide or would occur with other GLP-1 agonists. No rechallenge or dose-response data is provided.

How to read the evidence

This is a single case report — the lowest level of clinical evidence. It provides an important safety signal but cannot establish prevalence, causation, or risk factors. Published in JACC Case Reports, a high-quality cardiology journal.

When this study was published

Published in 2025, this is a very timely report as tirzepatide prescription for weight loss is rapidly increasing. The safety signal is new and has not yet been studied in larger cohorts of POTS patients.

The bigger picture

POTS affects an estimated 1-3 million Americans, with higher prevalence in young women — the same demographic increasingly using GLP-1/GIP drugs for weight management. As these peptide medications move beyond diabetes into mainstream obesity treatment, identifying populations at risk for adverse cardiovascular effects becomes critical. This case suggests autonomic disorders should be considered a potential risk factor for enhanced heart rate effects with incretin peptide drugs.

Questions still open

Is the exaggerated heart rate response specific to tirzepatide's dual GIP/GLP-1 agonism, or would single GLP-1 agonists have the same effect in POTS?
Should POTS patients be screened or monitored more closely when starting GLP-1/GIP peptide drugs?
What is the mechanism by which tirzepatide causes such a large heart rate increase in autonomic dysfunction patients?

Common questions

What is POTS and why might GLP-1 drugs make it worse?

POTS (Postural Orthostatic Tachycardia Syndrome) causes an abnormally large heart rate increase when standing up, leading to dizziness, lightheadedness, and fainting. GLP-1 drugs are known to slightly increase resting heart rate (~3 bpm), which is usually insignificant. But in POTS patients whose heart rate regulation is already impaired, this effect may be dramatically amplified — as this case showed with a 20-30 bpm increase.

Should people with POTS avoid tirzepatide?

This single case report cannot make that determination, but it raises an important caution. Patients with POTS who are considering tirzepatide or similar peptide drugs for weight loss should discuss potential cardiovascular effects with their doctor. Close heart rate monitoring after starting the medication would be prudent, and the patient's POTS management plan may need adjustment.

Read the original research

Exacerbation of Postural Orthostatic Tachycardia Syndrome With Tirzepatide Prescribed for Weight Loss.

JACC. Case reports, 30(32), 105430

View on PubMed ↗Publisher’s paper ↗

Citation

Hedge, Eric T; Grappe, Shannon R; Vernino, Steven; Almandoz, Jaime P; Levine, Benjamin D. (2025). Exacerbation of Postural Orthostatic Tachycardia Syndrome With Tirzepatide Prescribed for Weight Loss.. JACC. Case reports, 30(32), 105430. https://doi.org/10.1016/j.jaccas.2025.105430