Cardiovascular Safety Profile of GLP-1 RAs in Patients with Diabetes or Obesity

There is no significant link between the use of glucagon-like peptide-1 receptor agonists and arrhythmias in patients with type 2 diabetes or obesity.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) present a low risk for cardiac arrhythmias among people with type 2 diabetes (T2D) and obesity, according to a study published in Diabetology & Metabolic Syndrome.

Some patients with obesity or T2D undergo GLP-1 RA therapy to lose weight or control their glycemic levels. Researchers and practitioners have expressed concern over the effect that GLP-1 RAs might have on cardiovascular health, however. Because of the potential for GLP-1 RAs to increase heart rates, the authors of this study investigated the association between the use of this therapy and cardiac arrhythmias in patients with T2D and obesity.

The authors conducted a meta-analysis and systematic review of randomized controlled studies published on or before May 25, 2022 that appeared in searches of MEDLINE, EMBASE,, and the Cochrane Library.  Studies were included if they compared GLP-1 RAs with placebo or had active control groups of adults with T2Dor obesity. Outcome measures included incident atrial fibrillation, atrial flutter, ventricular arrhythmias (VA), and sudden cardiac death.

A total of 79,720 participants with a mean age of 57.3 from 56 randomized controlled trials were included in the analysis. The intervention group contained 44,028 participants, and 35,692 were in the control group. The researchers estimated Mantel-Haenszel relative risk (RR) with 95% CI, using a fixed-effects model. When comparing outcomes of patients in the two groups, the researchers found that GLP-1 RAs did not correlate with a statistically significant increase in the likelihood of incident atrial fibrillation (RR 0.97 [95% CI, 0.83-1.12]), atrial flutter (RR 0.83 [95% CI, 0.59-1.17]), VAs (RR 1.24 [95% CI, 0.92-1.67]), or sudden cardiac death (RR 0.89 [95% CI, 0.67-1.19]). After further analysis, the authors indicated that elevated doses of GLP-1 RA (RR 1.63 [95% CI, 1.11-2.40]) and higher baseline BMI (RR 1.60 [95% CI, 1.04-2.48]) might significantly heighten the risk for VA.

Given the increased risk of VAs, physicians should be more careful when treating obese subjects or prescribing high dosage.

The study had several limitations, including the wide confidence intervals that resulted from the inclusion of studies that contained relatively few arrhythmia cases. In addition, the authors indicated that analyzing studies that included both T2D and obesity resulted in a population heterogeneity that may t have affected the results of this study.

The researchers concluded that GLP-1 RA therapy is not significantly associated with an increased risk for arrhythmias among people with T2Dor obesity. The authors note that “given the increased risk of VAs, physicians should be more careful when treating obese subjects or prescribing high dosage.” In light of these findings, the authors suggest that more research is necessary to identify any drug-specific effects of GLP-1 RA and whether such effects vary by dose or BMI.


Wu S, Lu W, Chen Z, Dai Y, Chen K, Zhang S. Association of glucagon-like peptide-1 receptor agonists with cardiac arrhythmias in patients with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized controlled trials. Diabetol Metab Syndr. 2022;14:195. doi: 10.1186/s13098-022-00970-2