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10.1073/pnas.80.18.5485 80 LovicD.PiperidouA.ZografouI.GrassosH.PittarasA.ManolisA

Comments: Subcutaneous semaglutide 1 mg / week: 13 % improvement in walking distance vs placebo (med 26.4 m / avg 39.9 m) Improved quality of life (VascuQoL-6 and SF-36 questionnaires) Fewer rescue treatments vs placebo Improvement in ankle-brachial index (ABI) Modest weight loss of 4.1 kg with Semaglutide vs placebo Key benefits: Rapid benefit (from week 26) maintained over time (up to week 57) Improved performance on inclined treadmill Increased ABI, supporting a direct vascular benefit (anti-inflammatory action) Potential additional benefits: weight loss, cardiometabolic effects, renal benefits, major cardiovascular event reduction, heart failure benefits Limitations: Difficulty translating treadmill improvement to daily life activities Benefits may vary based on disease severity, functional demands, and patient expectations Study limited to diabetic patients Short-term evaluation of adverse major events Modest but statistically significant improvement in ABI warrants further mechanistic studies on PAD Other considerations: Weight loss and gastrointestinal effects may have revealed randomization, but unlikely to affect objective measures (walking distance or ABI) Other available medications: Pentoxifylline : Few benefits compared to placebo Cilostazol : Similar clinical improvement to Semaglutide Both increase walking distance without impact on cardiovascular health Get the latest clinical cases and breaking news delivered straight to your inbox!

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Ethics statement The studies involving human participants were reviewed and approved by CEIM SEVILLE

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