SGLT2 Inhibitors and Peripheral Vascular Events: A Review of the Literature

Elena Marchiori; Roman N Rodionov; Frederik Peters; Christina Magnussen; Joakim Nordanstig; Alexander Gombert; Konstantinos Spanos; Natalia Jarzebska; Christian-Alexander Behrendt

doi:10.1016/j.hfc.2022.03.001

SGLT2 Inhibitors and Peripheral Vascular Events: A Review of the Literature

Heart Fail Clin. 2022 Oct;18(4):609-623. doi: 10.1016/j.hfc.2022.03.001. Epub 2022 Aug 13.

Authors

Elena Marchiori¹, Roman N Rodionov², Frederik Peters³, Christina Magnussen⁴, Joakim Nordanstig⁵, Alexander Gombert⁶, Konstantinos Spanos⁷, Natalia Jarzebska⁸, Christian-Alexander Behrendt⁹

Affiliations

¹ Department of Vascular and Endovascular Surgery, University Hospital Münster, Münster, Germany.
² University Center for Vascular Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany; College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, Australia.
³ Research Group GermanVasc, Department of Vascular Medicine, University Heart and Vascular Center UKE Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
⁴ Department of Cardiology, University Heart & Vascular Centre Hamburg, Hamburg 20246, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Luebeck, Hamburg, Germany.
⁵ Institute of Medicine, Department of Molecular and Clinical Medicine, University of Gothenburg and Department of Vascular Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden.
⁶ European Vascular Centre Aachen-Maastricht, Department of Vascular Surgery, University Hospital RWTH Aachen, Aachen, Germany.
⁷ Vascular Surgery Department, Larissa University Hospital, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.
⁸ University Center for Vascular Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany.
⁹ Research Group GermanVasc, Department of Vascular Medicine, University Heart and Vascular Center UKE Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Brandenburg Medical School Theodor Fontane, Neuruppin, Germany. Electronic address: behrendt@hamburg.de.

PMID: 36216490
DOI: 10.1016/j.hfc.2022.03.001

Abstract

Fifty articles comprising 18 randomized controlled trials (RCTs), 16 observational studies, and 16 meta-analyses on the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors were evaluated in the current review. Only one-fourth of the cohorts of recent trials had peripheral arterial disease (PAD), whereas this subgroup was at high risk for amputations. Despite a remarkable heterogeneity of RCTs, only 2 trials on canagliflozin suggested excess amputation rates, whereas several observational studies generated conflicting conclusions and remained short on possible explanations. Preliminary evidence from observational research suggested that patients with PAD may even benefit from SGLT-2 inhibitor treatment due to lower observed heart failure hospitalization rates.

Keywords: Amputation; Diabetes; Drugs; Outcomes; Peripheral arterial disease; SGLT2 inhibitor.

Publication types

Review

MeSH terms

Canagliflozin
Diabetes Mellitus, Type 2*
Glucose
Humans
Hypoglycemic Agents / pharmacology
Sodium
Sodium-Glucose Transporter 2 Inhibitors* / pharmacology
Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

Hypoglycemic Agents
Sodium-Glucose Transporter 2 Inhibitors
Canagliflozin
Sodium
Glucose