Do GLP-1 RAs reduce VTE risk in T2D?

New data from a study of 656,588 patients with type 2 diabetes (T2D) demonstrate a lower risk of venous thromboembolism (VTE), regardless of obesity status, when treated with glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RAs).

VTE rates at 1 year were 20 percent lower in patients started on a GLP-1 RA than a dipeptidyl peptidase-4 (DPP-4) inhibitor (6.5 vs 7.9 cases per 1,000 person-years, hazard ratio [HR], 0.80, 95 percent confidence interval [CI], 0.75-0.85; p<0.001) in this retrospective, propensity-score matched multicentre database analysis. [ASH 2024, abstract 701]

The 20-percent risk reduction in VTE held across various subgroups of BMI, including those with obesity, said study investigator Dr Cho-Han Chiang from Mount Auburn Hospital, Cambridge, Massachusetts, US, who presented the findings at ASH 2024.

“The difference in VTE rates between groups became evident almost right after treatment initiation, added lead investigator Dr Rushad Patell, assistant professor of medicine at Harvard Medical School in Boston, Massachusetts, US.  “It could be beyond weight loss … If you’re selecting an antidiabetic agent for a patient and thrombotic risk comes into play, these data suggest that there may be some advantage to choosing a GLP-1 RA.”

Growing indications

GLP1-RAs are antihyperglycemic agents initially approved for the treatment of T2D. More recently, they gained traction for weight loss in patients with obesity.

“There are also data showing consistent cardiovascular benefits with GLP1-RA use in T2D, but those are limited to atherosclerotic disease,” said Patell.

As obesity is an established risk factor for VTE, he and his team sought to investigate if GLP-1 RAs could reduce the risk of VTE. They scoured electronic health records from the TriNetX global database, which include more than 250 million patients, and identified adults with T2D taking a GLP-1 RA or a DPP-4 inhibitor.

Patients on GLP-1 RAs were matched with those on DPP-4 inhibitors based on predetermined variables, including age, sex, race, BMI, HbA_1c, use of other antidiabetic agents, including metformin and insulin, and underlying comorbidities based on the components of the Charleston Comorbidity index.

VTE was a composite of pulmonary embolism (PE) and deep vein thrombosis (DVT). Patients were excluded if they already had a VTE, were on oral anticoagulation, or had atrial fibrillation. After propensity score matching, the final analysis included two cohorts of 168,428 patients each.

VTE rates comparable regardless of obesity status

In the subgroup analysis, VTE rates were similar for patients with and without obesity (HRs, 0.80 and 0.82, respectively). Irrespective of BMI at baseline, GLP-1 drugs remained associated with a lower risk of VTE at 1 year.

Among patients with the highest BMI (≥40), VTE occurred at a rate of 7.2 cases/1,000 person-years in the GLP-1 RA group vs 9.6 cases/1,000 person-years in the DPP-4 inhibitor group (HR, 0.74).

In those with a BMI of 30–34.9, VTE occurred at a rate of 4.8 cases/1,000 person-years in the GLP-1 RA group vs 7.9 cases/1,000 person-years in the DPP-4 inhibitor group (HR, 0.77).

Among those with the lowest BMI (18.5–24.9), VTE occurred significantly less frequently among those in the GLP-1 RA group at 4.7 cases/1,000 person-years vs 7.4 cases/1,000 person-years in the DPP-4 inhibitor group (HR, 0.61).

“Interestingly, the GLP-1 and DPP-4 curves started diverging within the first 30 days of the index prescription date,” reported Chiang.

Lower risks of PE and DVT

The lower risk of VTE associated with GLP-1 RAs also held across the individual components of the composite VTE. PE occurred at a rate of 3.1 cases/1,000 person-years in the GLP-1 RA group vs 3.9 cases/1,000 person-years in the DPP-4 inhibitor group (HR, 0.78, 95 percent confidence interval [CI], 0.71-0.85). DVT occurred in 4.2 cases/1,000 person-years in the GLP-1 RA group vs 5 cases/1,000 person-years in the DPP-4 inhibitor group (HR, 0.82,95 percent CI, 0.75-0.88).

“These results suggest that the use of GLP-1 RAs can lead to a reduction in VTE risk. This is important considering the growing number of patients experiencing VTE each year,” said Patell. “When we see patients with a blood clot, and there’s a need to prescribe anticoagulants – if obesity is a risk factor – we tell them about diet and exercise. But we shrug our shoulders and do not expect that to change. Finally, we have something now that can impact this risk factor.”

Cautious optimism

Session moderator Dr Ghadeer Dawwas from Vanderbilt University Medical Center in Nashville, Tennessee, US, commented that patients with T2D increasingly use GLP-1 RAs because of the cardiovascular benefits. However, the antithrombotic benefits are still under debate. “Given the current evidence landscape and the conflicting data on VTE risk, clinicians should proceed with caution and await further studies to validate these findings before making clinical decisions.”

Whether the results also extend to patients using GLP-1 RAs for weight control without T2D remains to be investigated.