Abstract Introduction Lower extremity peripheral artery disease (PAD) is caused by atherosclerotic steno-occlusive arterial lesions in the lower extremities and can lead to intermittent claudication, severe functional impairment and reduced health-related quality of life (HRQoL). People living with type 2 diabetes (T2D) are at higher risk of developing PAD than those without T2D. The most common clinical manifestation of PAD, functional impairment, can be stratified based on severity using Fontaine classification (stages I-IV). There are a limited number of therapies approved for the management of PAD related functional impairment and no glucose-lowering medication has been shown to improve functional capacity in people with PAD and T2D. STRIDE is a phase 3 clinical trial investigating once-weekly subcutaneous (s.c.) semaglutide treatment in people with PAD (Fontaine IIa claudication) and T2D. Purpose To report the patient-reported outcomes (PROs) at baseline from STRIDE and elucidate the impact that PAD has on the functional capacity and HRQoL in this early-stage symptomatic PAD population with T2D. Methods STRIDE enrolled 792 participants with PAD (Fontaine IIa claudication) and T2D who were randomised to receive either 1 mg once-weekly s.c. semaglutide or placebo for 52 weeks. The primary outcome of STRIDE is the change in maximum walking distance at week 52 on a constant load treadmill. Baseline PRO assessments included two Patient Global Impression of Severity (PGI-S) questions and three patient-reported questionnaires: the six items version of the Vascular Quality of Life questionnaire (VascuQoL-6), the Walking Impairment Questionnaire (WIQ) and the Medical Outcomes Short Form 36 (SF-36). Results Baseline responses to both PGI-S questions showed that two thirds of patients reported a moderate-to-severe limitation in their ability to walk (64.9%) and reported that the impact of poor blood circulation in their legs on their HRQoL was also moderate-to-severe (62.5%) (Figure 1A and B). The baseline VascuQoL-6 median score was 15 (score range: 6-24, with a low score indicating more severe impact) and details of impact on the six domains are presented in Table 1. Baseline responses to the WIQ indicated that 20.1% of participants found the degree of difficulty to walk 200 meters either ‘much difficulty’ or were ‘unable to do so’ and 21.8% reported the same when climbing 2 flights of stairs. The secondary supportive outcome assessed in the SF-36 questionnaire was the domain physical functioning where a median baseline value of 38.09 was observed (score range: 19.03-57.60, with a low score indicating more impact). Conclusion Participants in STRIDE, characterized as having early-stage symptomatic PAD, have reported moderate-to-high impact on their physical functioning and HRQoL at baseline. These findings highlight the need for better therapies that improve the functional capacity and HRQoL in people with PAD and T2D.