STRIDE Trial Results Show a Medication May Help PAD Patients Walk Farther

The STRIDE trial set out to answer a question that has been difficult to address in peripheral artery disease.

Can anything meaningfully improve how far patients are able to walk?

For years, exercise has remained the foundation of treatment. Patients are told to walk through discomfort to build collateral circulation.

Some are able to do it.

Many are not.

The STRIDE trial focused on walking capacity.

Led by Dr. Marc Bonaca at the University of Colorado School of Medicine, the study evaluated semaglutide in patients with peripheral artery disease and type 2 diabetes. In a phase 3b, double-blind, randomized, placebo-controlled trial involving 792 patients across 20 countries, researchers measured whether the medication could improve walking distance.

Patients receiving semaglutide walked about 40 meters farther than those on placebo during a six-minute walk test. In PAD research, a 20-meter improvement is considered clinically meaningful. This was double that and measured on a 12% incline.

The trial also showed improvement in ankle-brachial index, one of the standard measurements of blood flow in the legs.

“To my knowledge, it’s the first drug to show that you can improve that marker,” Dr. Bonaca said.

The results were not driven by weight loss.

“A lot of patients suffering with PAD don’t have obesity,” Dr. Bonaca noted. “It didn’t matter what your body weight change was.”

Researchers are now examining whether the medication has a direct effect on blood vessels, including the smaller vessels often affected in patients with diabetes.

“We have not had effective therapies for that in the past,” he said.

The origins of this work trace back to the LEADER trial, which showed that a related medication reduced diabetic foot ulcers and amputations by 30 to 40 percent. That observation led to further investigation into whether these therapies influence vascular disease more broadly.

STRIDE builds on that.

Dr. Bonaca has been clear about how this fits into care.

“Exercise therapy is the foundational treatment for PAD,” he said. “This does not replace that. It complements it.”

Exercise benefits diminish quickly when patients stop. Increasing walking distance may allow patients to remain active long enough to build collateral circulation.

The trial also showed a delay in the need for more invasive procedures such as stenting or bypass, which are not always durable and carry their own risks.

Researchers continue to analyze the data. Early findings suggest the benefit was consistent regardless of A1C levels, duration of diabetes, or background medications. Improvements were also seen in both men and women.

Regulatory review is underway. The European Medicines Agency has issued a positive opinion, and review in the United States is expected.

“The therapies are available,” Dr. Bonaca said. “We have data today.”

The STRIDE trial and the work led by Dr. Bonaca and his team were recognized by the Global PAD Association with the Breakthrough Walking as Therapy Research of the Year Award.

The award is not an endorsement of a specific therapy. It reflects progress in an area where options to improve function have been limited.

For patients, the next step is a conversation about walking limitation, circulation, and available options.

Questions to ask your doctor

• Has my walking limitation been evaluated with objective testing such as ABI or imaging?

• What is contributing most to my difficulty walking right now?

• Are there treatment options that focus on improving walking capacity?

• Would a therapy like the one studied in STRIDE apply to my situation?

• How does this fit with a structured walking or supervised exercise program?

• Should I be evaluated by a specialist in PAD or limb salvage?

  
  

This information is provided for educational purposes only. Your medical team determines the right tools and treatment approach based on your specific condition, your anatomy, and your overall health. You can ask about the information provided here, but it does not determine your care plan.