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ACC 25: Semaglutide Improves Function In PAD Patients With T2D In STRIDE Study
At the meeting of the American College of Cardiology (ACC) held in Chicago from 29 March to 31 March 2025, Novo Nordisk has announced the primary results of the Phase IIIb STRIDE trial investigating semaglutide's impact on walking capacity in people with symptomatic peripheral artery disease (PAD) and type 2 diabetes (T2D).
PAD is considered the first and most frequent manifestation of cardiovascular disease in patients with diabetes. There are few therapeutic and interventional options for patients with PAD, and the level of unmet need is therefore very high.
As they are approved for type 2 diabetes, guidelines recommend SGT2i and GLP-1R agonists for PAD in type 2 diabetes patients, but no drug class has shown PAD-specific benefits until STRIDE.
Many factors impact the incidence of PAD. Among these are inflammation, hyperglycaemia, hypertension and obesity, all of which have been shown to improve under GLP-1R agonist treatment.
The STRIDE trial showed that symptomatic PAD patients with type 2 diabetes treated with semaglutide 1mg for a year experienced substantial functional benefits related to their PAD compared to the placebo group.
Semaglutide statistically significantly improved maximum walking distance in patients – the main parameter to assess functional PAD improvement: 40 metres of difference being walked by the treatment group on a 12% gradient. (20 metres walked on a flat surface is considered a clinically meaningful improvement).
It is important to note that these benefits were consistent in the different subgroups (age, weight, background). A weak correlation between improvement in walking distance and body weight reduction was observed both in the placebo and semaglutide-treated groups, although considered not strong enough to account for the degree of improvement.
Pain-free walking distance and quality of life were also improved by semaglutide, and an approximately 54% lower hazard of progression of disease leading to revascularisation, major adverse limb events or all-cause death was observed in the semaglutide-treated group.
The tolerability and safety of semaglutide were consistent with other studies on GLP-1R agonists, with no serious adverse events observed in the trial, apart from the mild to moderate gastrointestinal symptoms commonly associated with the drug class.
In conclusion, in the STRIDE trial, semaglutide was shown to significantly improve function in patients with symptomatic PAD and type 2 diabetes in a clinically meaningful way, by improving walking capacity, symptoms of PAD, quality of life and haemodynamics, and by reducing PAD disease progression. After having proved its cardiometabolic benefits and kidney outcomes, semaglutide can now also be viewed as a therapeutic option specifically for PAD in type 2 diabetes patients, further increasing the patient population who can benefit from this medication.
Can You Lose Limbs If You Have Diabetes?
Unmanaged diabetes can lead to amputations, usually of the toes, feet, or legs. Causes include reduced blood flow or peripheral neuropathy. Managing your blood sugar may help prevent it.
Limb loss and amputation are a rare, but major complication of unmanaged diabetes.
This means around 0.3% of people with diabetes — or 1 in 300 people — receive an amputation yearly.
Diabetes management and amputation rates have improved in the last 20 years, but some research suggests that young and middle-aged adults in the United States are experiencing an uptick in diabetes-related amputations.
If you have diabetes, carefully following your management plan is key to preventing long-term complications.
Keep reading to learn more about how diabetes can lead to amputation and how to help prevent it.
Limb loss and amputation in diabetes are most commonly associated with long-term high blood sugar, blood pressure, or cholesterol levels, according to Diabetes UK.
There are two complications most commonly associated with leg amputations in diabetes: peripheral neuropathy and peripheral artery disease (PAD).
Peripheral neuropathy
Long-term high blood sugar levels, oxidative stress, and inflammation may cause nerve damage in the legs, feet, and toes. This is known as peripheral neuropathy.
If you can't feel pain, you may not realize you have a wound or ulcer on your feet. You may continue putting pressure on the affected area, which can cause it to grow and become infected.
Over time, wounds, ulcers, and infections can completely damage the nerves in your lower limbs, possibly leading to limb loss and amputation.
Peripheral artery disease (PAD)
Reduced blood flow can slow wound healing and make your body less effective at fighting infection, so your wound may not heal. Tissue damage or death (gangrene) may occur, and any existing infection may spread to your bone.
This may also result in amputation.
Good foot care may help you prevent wounds or ulcers from becoming problematic. Here are some foot care tips:
Report any foot problems and neuropathy symptoms, such as numbness, burning, and tingling, to a doctor right away.
What you can do now
Here are some things you can do now to help keep your feet healthy and prevent complications:
Diabetes is a chronic health condition characterized by high blood sugar levels.
If left unmanaged, diabetes may lead to complications that could affect the nerves and arteries in your legs. Over time, this may cause infections that can lead to amputation.
It's important to follow your diabetes management plan. Connect with a doctor as soon as possible if you experience symptoms like numbness, tingling, and ulcers in your legs.
Early detection and treatment are key to preventing amputation in diabetes.
This Drug Boosts Walking Ability In People With Type 2 Diabetes And Peripheral Artery Disease
A new international study has found that semaglutide, a medication commonly used to treat type 2 diabetes and obesity, significantly improves walking distance, symptoms, and quality of life in people with peripheral artery disease (PAD) and type 2 diabetes.
The trial, called STRIDE, is the first to test the use of a GLP-1 agonist for managing PAD and has been published in The Lancet.
PAD affects over 200 million people worldwide, including 12 million in the U.S. It occurs when fat and cholesterol build up in the arteries of the legs, reducing blood flow and making it painful or difficult to walk.
PAD can also lead to dangerous complications, including non-healing wounds, limb amputation, and death. Yet, treatment options are limited. The only approved drug for improving walking ability in PAD, cilostazol, has significant side effects and is not safe for people with heart failure, making it rarely used.
In the STRIDE trial, 792 adults with type 2 diabetes and early-stage symptomatic PAD were randomly assigned to receive semaglutide (1 mg weekly) or a placebo for 52 weeks. The participants were from 112 medical centers across 20 countries. Their average age was 67, about a quarter were women, and two-thirds were white.
Researchers measured participants' maximal walking distance on a treadmill at several points: at the start, after 26 weeks, after 52 weeks (the main assessment point), and again five weeks after stopping treatment.
At the beginning of the study, most patients were already quite impaired—they could only walk around 186 meters (roughly 0.1 miles) before symptoms like leg pain began.
By the end of the study, patients taking semaglutide had a median increase of 26 meters and an average improvement of 40 meters in how far they could walk—about a 13% improvement. While this may not sound like a lot, it's considered meaningful in the context of PAD, where even a 10- to 20-meter increase is seen as clinically important.
Improvements extended beyond walking distance. Patients taking semaglutide reported better quality of life, including less leg pain and more ability to walk without discomfort. These improvements lasted even five weeks after stopping the drug. They also showed increased blood flow in the legs, as measured by the ankle brachial index—a key test for PAD.
Additionally, a post-hoc analysis showed that patients on semaglutide were 54% less likely to need urgent treatment for worsening symptoms (like artery-opening procedures) or to die from related complications. Only 14 patients in the semaglutide group needed such interventions compared to 30 in the placebo group.
Lead researcher Dr. Marc Bonaca from the University of Colorado School of Medicine emphasized the significance of these findings.
"This is the first new option in decades that not only improves walking ability, but also symptoms, blood flow, and overall quality of life for people with PAD and diabetes," he said. "It may also help reduce the need for future invasive procedures."
One key takeaway is that the benefits of semaglutide in PAD seem to go beyond weight loss, which was modest in this study. The results hint at a possible direct effect on blood vessels, suggesting semaglutide may improve circulation independently of its weight-related effects.
This raises hope that the drug could potentially help people with PAD who do not have type 2 diabetes—a possibility researchers hope to explore in future trials.
The trial had some limitations. All participants had type 2 diabetes, so the findings can't yet be applied to people with PAD who don't. Also, the study population was not fully diverse—only 14% were enrolled in North America, and there were relatively few Black participants, which may limit how broadly the results apply.
Despite these limitations, the STRIDE trial represents a major step forward in the treatment of PAD. For the millions of people struggling with reduced mobility, pain, and the risk of serious complications, semaglutide may offer a new path to better health and a better life.
If you care about diabetes, please read studies about Vitamin D and type 2 diabetes, and what you need to know about avocado and type 2 diabetes.
For more information about diabetes, please see recent studies about how to eat to prevent type 2 diabetes, and 5 vitamins that may prevent complication in diabetes.
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