Semaglutide improves maximum walking distance in people with symptomatic pad and type 2 diabetes

Semaglutide improves maximum walking distance in people with symptomatic pad and type 2 diabetes

Semaglutide, a glucagon-like peptide 1 (GLP-1) agonist, improved maximum walking distance in people with symptomatic peripheral artery disease (PAD) and type 2 diabetes in the Art-IT-Art study evaluating the use of a GLP-1 agonist to treat PAD. In addition to improvements in walking abilities and functions, people who took semaglutide also saw significant improvements in both symptoms and quality of life compared to those who took a placebo.

PAD, which affects an estimated 12 million U.S. adults and over 200 million people worldwide, occurs when there is a buildup of fat and cholesterol, most commonly in the arteries of the legs. It is often associated with difficulty walking and poor circulation, which can lead to non-healing wounds and a high rate of limb loss. People with PAD are at very high risk for serious complications, including acute limb ischemia – similar to a heart attack or leg stroke – which can lead to limb amputation or death if not treated quickly. The last drug approved by the US Food and Drug Administration to improve functional outcomes in PAD was cilostazol in 2000.

Even in the very early stages of PAD, people can't walk well, but they often don't know it's Pad. You may say, “I just slowed down.” The only medication we have available that is contraindicated for symptoms recommended in people with heart failure has no benefits beyond improving symptoms and causes many side effects. Overall, it is used in less than 10% of people. Therefore, we really have limited options for improving functionality in PAD. The problem is that over the course of PAD, patients continue to receive revascularization procedures to open arteries and are at high risk for adverse cardiovascular and limb events. “

Marc P. Bonaca, MD, MPH, professor of medicine and director of vascular research at the University of Colorado School of Medicine in Aurora, Colorado, and the study's lead author

GLP-1 agonists are a class of medications currently used to treat type 2 diabetes, obesity, kidney disease, cardiovascular disease including atherosclerotic vascular disease, and heart failure. The study, called Stride, enrolled 792 people with early-stage type 2 diabetes and symptomatic PAD at 112 medical centers in 20 countries. Participants were on average 67 years old, about 25% were women and 67% were white. All were randomly assigned to receive semaglutide (1 mg) or placebo for one year (52 weeks). The researchers assessed maximum walking distance – the maximum distance the patients could walk on a treadmill at 2 miles per hour (similar to going up a moderate hill) with a score of 12%. Function was assessed at baseline (median maximum walking distance was 186 meters), week 26, week 52 (primary endpoint), and week 57 (five weeks after discontinuation of treatment).

"Despite the fact that people were recruited based on early-stage reporting, we observed that they were actually severely impaired and could only walk about a tenth of a mile earlier with the onset of symptoms," Bonaca said. "We saw that the drug clearly worked. After six months there was a clear early benefit that continued to increase for a year."

Overall, patients in the semaglutide arm had an average improvement in walking distance of 26 meters and an average improvement of 40 meters, representing a statistically significant improvement of 13% at one year.

"To put this into context, we normally think that an increase in walking distance from 10 meters to 20 meters in PAD is clinically important, so this has exceeded those expectations," he said.

The results were further supported by confirmatory secondary endpoints showing significant improvements in quality of life (measured by the Vascular Quality Questionnaire-6 score), including pain-free walking distance and sustained improvement in maximum walking distance at five weeks after cessation of therapy. Safety was similar to previous studies, with non-serious gastrointestinal side effects being the most commonly reported side effect in patients taking semaglutide.

Patients' ankle-brachial index, a measure of blood flow in the legs, was significantly improved compared to placebo. A post hoc analysis examining time to salvage treatment (the need for revascularization due to worsening symptoms) or death was also lower. Within one year of treatment, patients taking semaglutide had a 54% reduction in the risk of dying or having to receive a medication or procedure for open blocked arteries in the legs due to worsened symptoms compared to patients (14 patients versus 30 patients).

“Taken together, the data support semaglutide for people with pad and type 2 diabetes mellitus as a therapy with cardiometabolic, cardiovascular and renal benefits and improves function, symptoms and quality of life,” said Bonaca. "There is more work to be done to understand the mechanism of benefit as the population had a median [body mass index] of 28.6 and the relationship between outcome and weight loss was very weak. This coupled with the increase in ankle brachial index really suggests a direct vascular effect. This also raises the question of whether patients with PAD and without type 2 diabetes mellitus could benefit and this should be investigated in future studies."

The study was limited in that it was only in patients who also had type 2 diabetes. In addition, approximately 14% of the study population was enrolled in North America, while 57% was enrolled in Europe and 29% was enrolled in Asia. As a result, there were few black patients.

This study was funded by Novo Nordisk. It was simultaneously published online inThe LancetAt the time of presentation.

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