Abstract：
OBJECTIVE: The aim of this study was to assess the efficacy and safety of oral semaglutide vs sitagliptin in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment.
METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).
RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.
CONCLUSIONS: Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.
BACKGROUND: ClinicalTrials.gov NCT04017832.
BACKGROUND: This trial was funded by Novo Nordisk A/S, Søborg, Denmark.
METHODS: The Peptide Innovation for Early Diabetes Treatment (PIONEER) 12 trial was a randomised, double-dummy, active-controlled, parallel-group, Phase IIIa trial conducted over 26 weeks at 90 sites across the China region (including mainland China, Taiwan and Hong Kong) and five other countries. Adults aged ≥18 years (≥20 years in Taiwan) with a diagnosis of type 2 diabetes, HbA1c between 53 and 91 mmol/mol (inclusive) and treated with a stable daily dose of metformin were eligible for inclusion. Participants were randomised (1:1:1:1) using a web-based randomisation system to either once-daily oral semaglutide (3 mg, 7 mg or 14 mg) or once-daily oral sitagliptin 100 mg. Treatment allocation was masked to both participants and investigators. Randomisation was stratified according to whether participants were from the China region or elsewhere. The primary endpoint was change in HbA1c from baseline to week 26. The confirmatory secondary endpoint was change in body weight (kg) from baseline to week 26. All randomised participants were included in the full analysis set (FAS). All participants exposed to at least one dose of trial product were included in the safety analysis (SAS).
RESULTS: Of 1839 participants screened, 1441 were randomly assigned to oral semaglutide 3 mg (n=361), 7 mg (n=360), 14 mg (n=361) or sitagliptin 100 mg (n=359) and included in the FAS. A total of 1438 participants were included in the SAS. In total, 75.2% of participants were from the China region. A total of 1372 (95.2%) participants completed the trial and 130 participants prematurely discontinued treatment (8.3%, 8.6% and 15.0% for oral semaglutide 3 mg, 7 mg and 14 mg, respectively; 4.2% for sitagliptin 100 mg). Significantly greater reductions in HbA1c from baseline to week 26 were reported for all doses of oral semaglutide vs sitagliptin 100 mg. For oral semaglutide 3 mg, 7 mg and 14 mg vs sitagliptin 100 mg, the estimated treatment differences (ETDs [95% CI]) were -2 (-4, -1) mmol/mol, -8 (-9, -6) mmol/mol and -11 (-12, -9) mmol/mol, respectively. The corresponding ETDs (95% CI) in percentage points vs sitagliptin 100 mg were -0.2 (-0.3, -0.1), -0.7 (-0.8, -0.6) and -1.0 (-1.1, -0.8), respectively. Reductions in body weight were significantly greater for all doses of oral semaglutide vs sitagliptin 100 mg (ETD [95% CI] -0.9 [-1.4, -0.4] kg, -2.3 [-2.8, -1.8] kg and -3.3 [-3.8, -2.8] kg for 3 mg, 7 mg and 14 mg, respectively). In the subpopulation of participants from the China region (75.2% of trial participants), reductions in HbA1c and body weight from baseline to week 26 were similar to those seen in the overall population. The most frequent adverse events in the semaglutide treatment arms were gastrointestinal, although these were mostly transient and mild/moderate in severity.
CONCLUSIONS: Significantly greater reductions in both HbA1c and body weight over 26 weeks were seen with oral semaglutide 3 mg, 7 mg and 14 mg than with sitagliptin 100 mg in a predominantly Chinese population with type 2 diabetes inadequately controlled with metformin treatment. Oral semaglutide was generally well tolerated, with a safety profile consistent with that seen in the global PIONEER trials.
BACKGROUND: ClinicalTrials.gov NCT04017832.
BACKGROUND: This trial was funded by Novo Nordisk A/S, Søborg, Denmark.
摘要：
目的：本研究的目的是评估口服司马鲁肽与西格列汀在以二甲双胍治疗为基础的2型糖尿病患者中的疗效和安全性。
方法：早期糖尿病治疗的肽创新（PIONEER）12试验是一项随机试验，双假人,主动控制，平行组，IIIa期试验在中国地区（包括中国大陆，台湾和香港）和其他五个国家。年龄≥18岁（台湾≥20岁）诊断为2型糖尿病的成年人，HbA1c在53至91mmol/mol（包括端点）之间，并且用稳定的每日剂量的二甲双胍治疗是合格的。参与者使用基于网络的随机系统随机分组（1：1：1：1），每天口服一次司马鲁肽（3mg，7毫克或14毫克）或每日一次口服西格列汀100毫克。参与者和研究者都掩盖了治疗分配。根据参与者是否来自中国地区或其他地区对随机分组进行分层。主要终点是HbA1c从基线到第26周的变化。证实的次要终点是体重(kg)从基线到第26周的变化。所有随机参与者均纳入完整分析集（FAS）。所有暴露于至少一剂试验产品的参与者均纳入安全性分析（SAS）。
结果：在接受筛选的1839名参与者中，1441人被随机分配至口服司马鲁肽3mg（n=361），7毫克（n=360），14mg（n=361）或西格列汀100mg（n=359），并包括在FAS中。共有1438名参与者被纳入SAS。总的来说,75.2%的参与者来自中国。共有1372名（95.2%）参与者完成试验，130名参与者过早停止治疗（8.3%，口服司马鲁肽3mg的8.6%和15.0%，7毫克和14毫克，分别为4.2%，西格列汀100毫克）。据报道，所有剂量的口服司马鲁肽与西格列汀100mg相比，HbA1c从基线到第26周的下降幅度明显更大。对于口服司马鲁肽3毫克，7毫克和14毫克vs西格列汀100毫克，估计的治疗差异(ETDs[95%CI])为-2(-4，-1)mmol/mol，-8(-9,-6)mmol/mol和-11(-12,-9)mmol/mol,分别。相应的ETDs（95%CI）相对于西格列汀100mg的百分比为-0.2（-0.3，-0.1），-0.7（-0.8，-0.6）和-1.0（-1.1，-0.8），分别。与西格列汀100mg相比，所有剂量的口服司马鲁肽的体重减轻均明显更大（ETD[95%CI]-0.9[-1.4,-0.4]kg，-2.3[-2.8，-1.8]kg和-3.3[-3.8，-2.8]kg（3mg），7毫克和14毫克，分别)。在来自中国地区的参与者亚群中(75.2%的试验参与者)，从基线至第26周,HbA1c和体重的下降与总体人群相似.司马鲁肽治疗组中最常见的不良事件是胃肠道，尽管这些大多是短暂的和轻度/中度的严重程度。
结论：口服司马鲁肽3mg后，在26周内HbA1c和体重均显著降低，在以二甲双胍治疗为基础的2型糖尿病患者中，7mg和14mg高于西格列汀100mg。口服司马鲁肽一般耐受性良好，安全性与全球PIONEER试验一致。
背景：ClinicalTrials.govNCT04017832。
背景：该试验由NovoNordiskA/S资助，索堡,丹麦。
方法：早期糖尿病治疗的肽创新（PIONEER）12试验是一项随机试验，双假人,主动控制，平行组，IIIa期试验在中国地区（包括中国大陆，台湾和香港）和其他五个国家。年龄≥18岁（台湾≥20岁）诊断为2型糖尿病的成年人，HbA1c在53至91mmol/mol（包括端点）之间，并且用稳定的每日剂量的二甲双胍治疗是合格的。参与者使用基于网络的随机系统随机分组（1：1：1：1），每天口服一次司马鲁肽（3mg，7毫克或14毫克）或每日一次口服西格列汀100毫克。参与者和研究者都掩盖了治疗分配。根据参与者是否来自中国地区或其他地区对随机分组进行分层。主要终点是HbA1c从基线到第26周的变化。证实的次要终点是体重(kg)从基线到第26周的变化。所有随机参与者均纳入完整分析集（FAS）。所有暴露于至少一剂试验产品的参与者均纳入安全性分析（SAS）。
结果：在接受筛选的1839名参与者中，1441人被随机分配至口服司马鲁肽3mg（n=361），7毫克（n=360），14mg（n=361）或西格列汀100mg（n=359），并包括在FAS中。共有1438名参与者被纳入SAS。总的来说,75.2%的参与者来自中国。共有1372名（95.2%）参与者完成试验，130名参与者过早停止治疗（8.3%，口服司马鲁肽3mg的8.6%和15.0%，7毫克和14毫克，分别为4.2%，西格列汀100毫克）。据报道，所有剂量的口服司马鲁肽与西格列汀100mg相比，HbA1c从基线到第26周的下降幅度明显更大。对于口服司马鲁肽3毫克，7毫克和14毫克vs西格列汀100毫克，估计的治疗差异(ETDs[95%CI])为-2(-4，-1)mmol/mol，-8(-9,-6)mmol/mol和-11(-12,-9)mmol/mol,分别。相应的ETDs（95%CI）相对于西格列汀100mg的百分比为-0.2（-0.3，-0.1），-0.7（-0.8，-0.6）和-1.0（-1.1，-0.8），分别。与西格列汀100mg相比，所有剂量的口服司马鲁肽的体重减轻均明显更大（ETD[95%CI]-0.9[-1.4,-0.4]kg，-2.3[-2.8，-1.8]kg和-3.3[-3.8，-2.8]kg（3mg），7毫克和14毫克，分别)。在来自中国地区的参与者亚群中(75.2%的试验参与者)，从基线至第26周,HbA1c和体重的下降与总体人群相似.司马鲁肽治疗组中最常见的不良事件是胃肠道，尽管这些大多是短暂的和轻度/中度的严重程度。
结论：口服司马鲁肽3mg后，在26周内HbA1c和体重均显著降低，在以二甲双胍治疗为基础的2型糖尿病患者中，7mg和14mg高于西格列汀100mg。口服司马鲁肽一般耐受性良好，安全性与全球PIONEER试验一致。
背景：ClinicalTrials.govNCT04017832。
背景：该试验由NovoNordiskA/S资助，索堡,丹麦。
