Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, Netherlands.
Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, Netherlands.
Curr Drug Saf. 2021;16(1):62-72. doi: 10.2174/1574886315666200805103053.
Treatment with sodium-glucose co-transporter-2-inhibitors (SGLT2-Is), such as canagliflozin, has been associated with an increased risk of lower limb amputations (LLAs) in type 2 diabetes mellitus (T2DM). However, conflicting results have been reported for different SGLT2-Is and the underlying mechanism is unclear.
To investigate the risk of LLA and diabetic foot ulcer with SGLT2-I use compared to other anti-diabetic drugs and to explore hypovolemia as a potential underlying mechanism.
A cohort study was conducted using data from the Clinical Practice Research Datalink GOLD (2013-2019). The study population (N=51,847) consisted of T2DM patients over 18 years of age with at least one prescription of a non-insulin anti-diabetic drug. Concomitant diuretic use and the presence of signs of hypovolemia were determined to assess the potential underlying mechanism. Cox proportional hazard models were used to estimate the hazard ratio (HR) for LLA in current SGLT2-I use versus current sulphonylurea (SU) use. Analyses were adjusted for lifestyle variables, comorbidities, and concomitant drug use.
Current SGLT2-I use was not associated with an increased risk of LLA compared to current SU use (fully adjusted HR 0.70; 95% confidence interval 0.38-1.29). Concomitant use of diuretics and the presence of signs of hypovolemia were not associated with an increased risk of LLA.
Use of SGLT2-Is, with or without signs of hypovolemia, was not associated with an increased risk of LLA or DFU versus current SU use. Future studies powered to detect potential differences between individual SGLT2-Is are required to rule out a canagliflozin-specific effect.
钠-葡萄糖共转运蛋白 2 抑制剂（SGLT2-Is）的治疗，如卡格列净，与 2 型糖尿病（T2DM）患者的下肢截肢（LLA）风险增加相关。然而，不同 SGLT2-Is 的结果存在冲突，其潜在机制尚不清楚。
研究 SGLT2-I 与其他抗糖尿病药物相比，LLA 和糖尿病足溃疡的风险，并探讨低血容量作为潜在的潜在机制。
使用临床实践研究数据链接 GOLD（2013-2019）的数据进行队列研究。研究人群（N=51847）由年龄在 18 岁以上且至少有一次非胰岛素抗糖尿病药物处方的 T2DM 患者组成。同时使用利尿剂和存在低血容量体征来评估潜在的潜在机制。使用 Cox 比例风险模型估计当前 SGLT2-I 与当前磺脲类药物（SU）使用相比，LLA 的风险比（HR）。分析调整了生活方式变量、合并症和同时使用的药物。
与当前 SU 相比，当前 SGLT2-I 治疗与 LLA 风险增加无关（完全调整后的 HR 0.70；95%置信区间 0.38-1.29）。同时使用利尿剂和存在低血容量体征与 LLA 风险增加无关。
与当前 SU 相比，使用 SGLT2-Is 无论是否存在低血容量体征，与 LLA 或 DFU 的风险增加无关。需要进行未来的研究，以检测个体 SGLT2-Is 之间潜在差异，以排除卡格列净特异性影响。
