Initiation of SGLT2 Inhibitors and the Risk of Lower Extremity Minor and Major Amputation in Patients with Type 2 Diabetes and Peripheral Arterial Disease: A Health Claims Data Analysis.

Roman N Rodionov, Frederik Peters, Ursula Marschall, Helmut L'Hoest, Natalia Jarzebska, Christian-Alexander Behrendt

Journal: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery 2022;62(6):981-990

PMID: 34782230

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Abstract

OBJECTIVE

To assess the association between long term risk of hospitalisation for heart failure (HHF) and lower extremity minor and major amputation (LEA) in patients initiating sodium glucose cotransporter 2 inhibitors (SGLT2i) suffering from type 2 diabetes and peripheral arterial disease (PAD). Outcomes were compared with patients without PAD and evaluated separately for the time periods before and after the official warning of the European Medicines Agency (EMA) in early 2017.

METHODS

This study used BARMER German health claims data including all patients suffering from type 2 diabetes initiating SGLT2i therapy between 1 January 2013 and 31 December 2019 with follow up until the end of 2020. New users of glucagon like peptide 1 receptor agonists (GLP1-RAs) were used as active comparators. Inverse probability weighting with truncated stabilised weights was used to adjust for confounding, and five year risks of HHF and LEA were estimated using Cox regression. Periods before and after the EMA warning were analysed separately and stratified by presence of concomitant PAD.

RESULTS

In total, 44 284 (13.6% PAD) and 56 878 (16.3% PAD) patients initiated SGLT2i or GLP1-RA, respectively. Before the EMA warning, initiation of SGLT2i was associated with a lower risk of HHF in patients with PAD (hazard ratio, HR, 0.85, 95% confidence interval, CI, 0.73 - 0.99) and a higher risk of LEA in patients without PAD (HR 1.79, 95% CI 1.04 - 2.92). After the EMA warning, the efficacy and safety endpoints were no longer statistically different between groups.

CONCLUSION

The results from this large nationwide real world study highlight that PAD patients exhibit generally high amputation risks. This study refutes the idea that the presence of PAD explains the excess LEA risk associated with initiation of SGLT2i. The fact that differentials among study groups diminished after the EMA warning in early 2017 emphasises that regulatory surveillance measures worked in everyday clinical practice.

Address: University Centre 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.; Research Group GermanVasc, Department of Vascular Medicine, University Heart and Vascular Centre UKE Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.; BARMER, Wuppertal, Germany.; University Centre for Vascular Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany; Clinical Sensoring and Monitoring, Department of Anaesthetics and Intensive Care Medicine, University Clinic Carl Gustav Carus, Technische Universität Dresden, Germany.; Research Group GermanVasc, Department of Vascular Medicine, University Heart and Vascular Centre UKE Hamburg, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany. Electronic address: [email protected].

DOI: 10.1016/j.ejvs.2021.09.031