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Abstract：
There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice.
Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria.
A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2).
This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials.
ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.
Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria.
A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2).
This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials.
ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.
摘要：
背景：很少有大规模的研究评估钠-葡萄糖协同转运蛋白-2抑制剂的安全性，dapagliflozin,中国2型糖尿病患者。Donate,一个多中心，单臂,prospective,非干预性研究，是第一个在常规临床实践中评估dapagliflozin在中国2型糖尿病患者中安全性的真实世界研究。
方法：在2017年8月至2020年7月之间，从中国88家医院前瞻性招募了开始达格列净治疗并接受≥1剂的2型糖尿病患者。随后对患者进行24周随访；如果患者停用达格列净，则在停药后再随访7天。主要结果是发生不良事件和严重不良事件的患者比例。特别是关键的不良事件（AESI），包括尿路感染，生殖道感染（有或没有微生物学诊断的典型症状）和低血糖（有或没有血糖≤3.9mmol/L的典型症状，或血糖≤3.9mmol/L，无症状）。探索性结果包括代谢参数的绝对变化和其他AESI患者的比例，包括容量消耗，血液电解质异常,多尿,肾功能损害，糖尿病酮症酸中毒,肝功能损害和血尿。
结果：共纳入3000例患者，其中2990人(99.7%)被纳入安全性分析集.平均（SD）年龄为52.6（12.0）岁，65.8%的患者为男性。2型糖尿病的平均持续时间（SD）为8.4（7.1）年。达格列净的平均（SD）治疗时间为209.1（157.6）天。在24周随访期间，35.4％（n=1059）的患者报告了不良事件。总的来说,9.0%(n=268)与治疗相关，6.2%(n=186)与治疗相关。尿路感染,生殖道感染和低血糖报告为2.3％（n=70），1.3%(n=39)和1.1%(n=32)的患者，分别。患有其他AESI的患者比例也较低：多尿（0.7％；n=21），体积消耗（0.3%；n=9），肾损害（0.3%；n=8），肝功能损害（0.2%；n=7），血尿（0.2％;n=6）和糖尿病酮症酸中毒（0.1％;n=2）。
结论：这项研究表明，中国2型糖尿病患者对每日一次达格列净的耐受性良好，达格列净在中国临床实践中的总体安全性与临床试验中的报告一致。
背景：ClinicalTrials.gov，NCT03156985。5月16日登记,2017.
方法：在2017年8月至2020年7月之间，从中国88家医院前瞻性招募了开始达格列净治疗并接受≥1剂的2型糖尿病患者。随后对患者进行24周随访；如果患者停用达格列净，则在停药后再随访7天。主要结果是发生不良事件和严重不良事件的患者比例。特别是关键的不良事件（AESI），包括尿路感染，生殖道感染（有或没有微生物学诊断的典型症状）和低血糖（有或没有血糖≤3.9mmol/L的典型症状，或血糖≤3.9mmol/L，无症状）。探索性结果包括代谢参数的绝对变化和其他AESI患者的比例，包括容量消耗，血液电解质异常,多尿,肾功能损害，糖尿病酮症酸中毒,肝功能损害和血尿。
结果：共纳入3000例患者，其中2990人(99.7%)被纳入安全性分析集.平均（SD）年龄为52.6（12.0）岁，65.8%的患者为男性。2型糖尿病的平均持续时间（SD）为8.4（7.1）年。达格列净的平均（SD）治疗时间为209.1（157.6）天。在24周随访期间，35.4％（n=1059）的患者报告了不良事件。总的来说,9.0%(n=268)与治疗相关，6.2%(n=186)与治疗相关。尿路感染,生殖道感染和低血糖报告为2.3％（n=70），1.3%(n=39)和1.1%(n=32)的患者，分别。患有其他AESI的患者比例也较低：多尿（0.7％；n=21），体积消耗（0.3%；n=9），肾损害（0.3%；n=8），肝功能损害（0.2%；n=7），血尿（0.2％;n=6）和糖尿病酮症酸中毒（0.1％;n=2）。
结论：这项研究表明，中国2型糖尿病患者对每日一次达格列净的耐受性良好，达格列净在中国临床实践中的总体安全性与临床试验中的报告一致。
背景：ClinicalTrials.gov，NCT03156985。5月16日登记,2017.
