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Tirzepatide and the Incidence of Atrial Fibrillation in Adults With Overweight or Obesity: An Updated Meta‐Analysis of Randomized Controlled Trials
Key result
Tirzepatide shows no increased risk of atrial fibrillation versus placebo in overweight or obese adults.
- OR 2.20
- 95% CI 0.81-6.75
- n=6,515
Why the study?
The effects of tirzepatide on the incidence of atrial fibrillation in patients with overweight or obesity remain unclear.
Does tirzepatide increase the incidence of atrial fibrillation in adults with overweight or obesity?
Key Points
- To evaluate whether tirzepatide is associated with an increased incidence of atrial fibrillation or other arrhythmias in adults with overweight or obesity.
- Systematic search of PubMed, Embase, and Cochrane Library identified 10 randomized controlled trials comparing tirzepatide with placebo in adults with overweight or obesity (N=6,515; 4,491 assigned to tirzepatide).
- Pooled odds ratios (ORs) with 95% credible intervals (CrIs) were calculated using a Bayesian binomial-normal hierarchical model suited for rare-event outcomes.
- Tirzepatide was not significantly associated with atrial fibrillation (pooled OR 2.20; 95% CrI, 0.81–6.75) or atrial arrhythmia (pooled OR 2.16; 95% CrI, 0.90–5.87).
Study Design
Type
Meta-Analysis (n=6,515)
Structured PICO
Does tirzepatide increase the incidence of atrial fibrillation in adults with overweight or obesity?
P
Population
6,515 adults with overweight or obesity included across 10 randomized controlled trials.
I
Intervention
Tirzepatide
C
Comparator
Placebo
O
Outcome
Incidence of atrial fibrillationsafety
Main Result
Odds Ratio: 2.2 (95% CI 0.81–6.75)
Tirzepatide is not significantly associated with an increased risk of atrial fibrillation or atrial arrhythmias in overweight or obese adults, though a slight increase in overall arrhythmias was observed and warrants cautious interpretation.
Limitations
- Event rates were low and the findings should be interpreted cautiously
- low event rates
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Although no clear association with AF or atrial arrhythmia was observed, the effect estimates for any arrhythmias suggested higher odds with tirzepatide. Because arrhythmias were not prespecified endpoints in most trials and event counts were low, these findings should be considered exploratory.”
SASana Al-KhatibElectrophysiologist, Duke University Medical Center
“based on the collective evidence, I think there is a pretty good signal that GLP-1s are associated with a reduction in the risk of atrial fibrillation.”
Implication
No significant AF risk with tirzepatide; leaves open arrhythmia signal for larger trials.
Abstract
BACKGROUND: Tirzepatide is a dual agonist for glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, with proven efficacy in weight loss and improvement in cardiovascular outcomes. However, the effects of tirzepatide on the incidence of atrial fibrillation in patients with overweight or obesity remain unclear. METHODS: PubMed, Embase, and Cochrane Library were searched for randomized controlled trials comparing tirzepatide versus placebo for individuals with overweight or obesity. Odds ratios (ORs) with 95% credible intervals (CrIs) were pooled using a Bayesian binomial-normal hierarchical model, appropriate for rare-event outcomes. RESULTS: Our meta-analysis included 10 randomized controlled trials, including 6515 individuals, of whom 4491 (68.9%) were randomized to tirzepatide. The pooled OR was 2.20 (95% CrI, 0.81-6.75) for atrial fibrillation, 2.16 (95% CrI, 0.90-5.87) for atrial arrhythmia, and 1.84 (95% CrI, 1.04-3.90) for any arrhythmia. CONCLUSIONS: Tirzepatide was not associated with atrial fibrillation or atrial arrhythmia. Although higher odds of overall arrhythmias were observed, event rates were low and the findings should be interpreted cautiously.
Discussion
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Cite This Study
Mansouri et al. (2026) conducted a meta-analysis in overweight or obesity (n=6,515). Tirzepatide vs. placebo was evaluated on atrial fibrillation (OR 2.20, 95% CI 0.81-6.75). Tirzepatide was not associated with an increased incidence of atrial fibrillation (OR 2.20; 95% CrI 0.81-6.75) compared to placebo in adults with overweight or obesity.