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Review
. 2025 Aug 6;14(15):5549.
doi: 10.3390/jcm14155549.

SGLT2 Inhibitors and GLP-1 Receptor Agonists in PAD: A State-of-the-Art Review

Alfredo Caturano  1 , Damiano D'Ardes  2 , Paola Giustina Simeone  2 , Gianfranco Lessiani  3 , Nicoletta Di Gregorio  4 , Lorenzo Andreetto  5 , Davide Grassi  6 , Carla Serra  7   8 , Francesca Santilli  2 , Maria Teresa Guagnano  2 , Fabio Piscaglia  7   9 , Claudio Ferri  4 , Francesco Cipollone  2 , Andrea Boccatonda  7   8
Affiliations
Review

SGLT2 Inhibitors and GLP-1 Receptor Agonists in PAD: A State-of-the-Art Review

Alfredo Caturano et al. J Clin Med. .

Abstract

Sodium-glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation.

Keywords: GLP-1 receptor agonists (GLP-1 RAs); amputation risk; cardiovascular outcomes; peripheral artery disease (PAD); sodium–glucose co-transporter-2 inhibitors (SGLT2is); type 2 diabetes mellitus (T2DM).

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Conflict of interest statement

The authors declare no conflicts of interest.

References

    1. Hinchliffe R.J., Forsythe R.O., Apelqvist J., Boyko E.J., Fitridge R., Hong J.P., Katsanos K., Mills J.L., Nikol S., Reekers J., et al. Guidelines on diagnosis, prognosis, and management of peripheral artery disease in patients with foot ulcers and diabetes (IWGDF 2019 update) Diabetes Metab. Res. Rev. 2020;36((Suppl. S1)):e3276. doi: 10.1002/dmrr.3276. - DOI - PubMed
    1. Boccatonda A., D’Ardes D., Moronti V., Santilli J., Cipollone A., Lessiani G., Di Gregorio N., Serra C., Piscaglia F., Ferri C., et al. From MASLD to PAD: Looking for Cardiovascular Disease Starting from Metabolic Status. Medicina. 2024;60:1781. doi: 10.3390/medicina60111781. - DOI - PMC - PubMed
    1. Younes A.M., Salem M., Maraey A., Nomigolzar S., Sewell K., Khalil M., Elzanaty A., Saeyeldin A., Dar M. Safety outcomes of SGLT2i in the heart failure trials: A systematic review and Meta-analysis. Int. J. Cardiol. 2022;366:51–56. doi: 10.1016/j.ijcard.2022.06.059. - DOI - PubMed
    1. Yan Y., Liu B., Du J., Wang J., Jing X., Liu Y., Deng S., Du J., She Q. SGLT2i versus ARNI in heart failure with reduced ejection fraction: A systematic review and meta-analysis. ESC Heart Fail. 2021;8:2210–2219. doi: 10.1002/ehf2.13313. - DOI - PMC - PubMed
    1. Kocabas U., Ergin I., Yavuz V., Altın C., Kaplan M., Öztekin G.M.Y., Doğduş M., Murat S., Murat B., Kıvrak T., et al. Real-world data on Empagliflozin and Dapagliflozin use in patients with HEART failure: The RED-HEART study. ESC Heart Fail. 2025;12:434–446. doi: 10.1002/ehf2.15049. - DOI - PMC - PubMed

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