Real‐world risk of lower‐limb amputation associated with sodium–glucose cotransporter 2 inhibitors versus metformin: A propensity score‐matched model analysis in Japan

• Published in: Journal of diabetes investigation Vol. 13; no. 12; pp. 2000 - 2009
• Main Authors: Mizutani, Gen, Horii, Takeshi, Oikawa, Yoichi, Atsuda, Koichiro, Shimada, Akira
• Format: Journal Article
• Language: English
• Published: Richmond John Wiley & Sons, Inc 01.12.2022; John Wiley and Sons Inc; Wiley
• Subjects: Age; Amputation; Anticoagulants; Antidiabetics; Body mass index; Diabetes; Diabetes mellitus (non-insulin dependent); Drugs; Glucagon; Glucose; Hyperglycemia; Insulin; Lower‐limb amputation; Metabolism; Metformin; Na+/glucose cotransporter; Original; Patients; Peptides; Sodium; Sodium–glucose cotransporter 2 inhibitor; Statins; Type 2 diabetes; Japan
• ISSN: 2040-1116; 2040-1124
• DOI: 10.1111/jdi.13906

ABSTRACT Aims/Introduction We aimed to clarify the real‐world risk of lower‐limb amputation and identify factors related to increased risk in Japanese patients with type 2 diabetes using sodium–glucose cotransporter 2 inhibitors (SGLT2is). Materials and Methods We carried out a retrospective observational cohort study utilizing the Japanese Medical Data Vision, a diagnosis procedure combination database. We identified 107,296 patients with type 2 diabetes who were initiated on SGLT2is or metformin (control; n = 53,648 per group) using 1:1 propensity score matching from April 2014 to October 2019. The hazard ratio (HR) for the risk of lower‐limb amputation was analyzed using a Cox proportional hazards model adjusted for patients' baseline characteristics and use of concomitant medical agents. Results Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. There was no significant difference in the risk of amputation between the SGLT2is and metformin groups (HR 1.34, 95% confidence interval [CI] 0.80–2.24). However, female sex (HR 2.78, 95% CI 1.12–6.94) and use of strong statins (HR 2.68; 95% CI 1.18–8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group. Conclusions SGLT2is might not be related to an increased risk of lower‐limb amputation in patients with type 2 diabetes in real‐world clinical practice. The possible increased risk of SGLT2is‐associated amputation in female patients with type 2 diabetes and patients with type 2 diabetes requiring strong statins is notable. We aimed to clarify the real‐world risk of lower‐limb amputation and identify factors associated with increased risk in Japanese patients with type 2 diabetes using sodium–glucose cotransporter 2 inhibitors (SGLT2is). Of the 107,296 patients, 66 (0.06%); that is, 41 (0.08%) in the SGLT2is group and 25 (0.05%) in the metformin group, underwent amputation, with no significant difference in the proportions between the groups. Although there was no significant difference in the risk of amputation between the SGLT2is and metformin groups (hazard ratio 1.34, 95% confidence interval 0.80–2.24), female sex (hazard ratio: 2.78; 95% confidence interval 1.12–6.94) and use of strong statins (hazard ratio 2.68; 95% confidence interval 1.18–8.20) were significantly associated with a higher risk of amputation in the SGLT2is group than in the metformin group.