Meysam Alipour
1 
, Jalal Rezaei
2 , Venus Shahabi Rabori
3 , Meysam Arbuzia
4,5 , Amin Norouzbeygi
6 , Sara Rasta
7 , Hossein Mardanparvar
8,9 , Mobin Forghan
10* 1 Department of Orthopedic, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Critical Care Nursing, School of Nursing and Midwifery, Tehran University of Medical Sciences, Tehran, Iran
3 International Training Fellow of Cardiology, WWL NHS Trust, Wigan, United Kingdom (UK)
4 Department of Nursing, Faculty of Nursing and Midwifery, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
5 Department of Nursing, Qeshm Branch, Islamic Azad University, Qeshm, Iran
6 Department of Orthopedic and Trauma Surgery, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
7 Department of Emergency Medicine, Imam Hossein Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
8 Endocrinology and Metabolism Research Center, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
9 Guissu Research Corporation, Bandar Abbas, Iran
10 Department of Orthopedic, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran
Abstract
This review article examines the association between sodium-glucose cotransporter type 2 inhibitors (SGLT2i) and the risk of limb amputation, particularly in patients with type 2 diabetes mellitus. This review aims to provide a comprehensive understanding of the risks associated with SGLT2i therapy and to inform future research directions in this area. While SGLT2i medications, such as canagliflozin, are recognized for their cardiovascular and renal benefits, emerging evidence suggests a potential increase in the risk of lower limb amputations (LLAs) among users compared to non-users of SGLT2i. This review synthesizes findings from various studies that report a slightly elevated risk of amputation linked to SGLT2i therapy, with mechanisms proposed including diuretic-induced hypovolemia and the partial inhibition of sodium-glucose cotransporter 1. Factors such as pre-existing peripheral artery disease (PAD), sensory neuropathy, and poor foot health are identified as significant risk enhancers for lower limb amputations in this patient population. In conclusion, patients with these conditions are at increased risk of limb ischemia and subsequent amputation, and the administration of SGLT2 inhibitors may potentially further increase this risk.