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.
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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.
Benefits were consistent across age, weight and background
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.
