Company
announcement
Oral semaglutide shows superior improvement in HbA 1c
vs empagliflozin in the PIONEER 2 trial
Bagsværd, Denmark, 29 May 2018 - Novo Nordisk today announced the headline
results from PIONEER 2, the second phase 3a trial with oral semaglutide for treatment of
adults with type 2 diabetes. Oral semaglutide is a new GLP-1 analogue taken once daily
as a tablet. The 52-week, open label trial investigated the efficacy and safety of 14 mg
oral semaglutide compared with 25 mg empagliflozin in 816 people with type 2 diabetes,
inadequately controlled on metformin. The confirmatory endpoints were defined after 26
weeks of treatment.
Two distinct statistical approaches to evaluating the effects of oral semaglutide were
applied in the PIONEER 2 trial; a primary statistical approach 1 required by recent
regulatory guidance evaluating the effect regardless of discontinuation of treatment and
use of rescue medication, and a secondary statistical approach 2 describing the effect
while on treatment and without use of rescue medication.
The trial achieved its primary objective according to the primary statistical approach by
demonstrating a statistically significant and superior improvement in HbA 1c with oral
semaglutide compared to empagliflozin at 26 weeks. Difference in weight loss at 26
weeks between oral semaglutide and empagliflozin was not statistically significant when
applying the primary statistical approach.
When applying the secondary statistical approach, people treated with 14 mg oral
semaglutide achieved a statistically significant improvement in HbA 1c of 1.4% at 26
weeks and 1.3% at 52 weeks, compared to an improvement in HbA 1c of 0.9% and 0.8%
with 25 mg empagliflozin at 26 and 52 weeks, respectively. The 14 mg dose of oral
semaglutide demonstrated weight loss of 4.2 kg at 26 weeks and 4.7 kg at 52 weeks
versus 3.8 kg with 25 mg empagliflozin at both 26 weeks and 52 weeks. The increased
weight loss with oral semaglutide was statistically significant compared to empagliflozin
at the 52-week time point.
In addition, applying the secondary statistical approach, the American Diabetes
Association (ADA) treatment target of HbA 1c below 7.0% was achieved by 72% of people
treated with 14 mg oral semaglutide compared with 47% of people treated with 25 mg
empagliflozin at 52 weeks.
In the trial, oral semaglutide was well-tolerated and with a profile consistent with GLP-1-
based therapy. The most common adverse event for oral semaglutide was mild to
moderate nausea, which diminished over time. In PIONEER 2, 20% of people treated
with oral semaglutide experienced nausea during the trial. The proportion of subjects
who discontinued treatment due to adverse events was 11% for people treated with 14
mg oral semaglutide compared to 4% for people treated with 25 mg empagliflozin.
“We are very excited about these results, which demonstrate that people treated with 14
mg oral semaglutide for one year achieved statistically significant reductions in blood
glucose and body weight compared to people treated with 25 mg empagliflozin,” said
Mads Krogsgaard Thomsen, executive vice president and chief science officer of Novo
Nordisk. “PIONEER 2 is an important milestone in the clinical development of oral
semaglutide and we look forward to further understanding the clinical profile of oral
semaglutide in the remaining PIONEER trials.”
About PIONEER 2 and the PIONEER clinical trial programme
PIONEER 2 was a 52-week, randomised, open-label, active-controlled, parallel-group,
multicentre, multinational trial with two arms comparing the efficacy and safety of oral
semaglutide with empagliflozin in people with type 2 diabetes mellitus, inadequately
controlled on metformin. 816 people were enrolled in PIONEER 2 and randomised 1:1 to
receive either 14 mg oral semaglutide or 25 mg empagliflozin once daily. The
confirmatory endpoints were change in HbA 1c and body weight from baseline to week 26.
Key secondary endpoints included change in HbA 1c and body weight from baseline to
week 52.
The PIONEER phase 3a clinical development programme for oral semaglutide is a global
development programme with enrolment of 8,845 people with type 2 diabetes across 10
clinical trials, which are all expected to complete in 2018.
1 Treatment policy estimand approach: treatment effect regardless of discontinuation of treatment or initiation
of rescue medication (analysed by pattern mixture model using multiple imputations to handle missing week 26
data).
2 Hypothetical estimand approach: The treatment effect of oral semaglutide versus empagliflozin for all
randomised subjects while on treatment without use of rescue medication (analysed by Mixed Models for
Repeated Measurements (MMRM)). Similar statistical methodology as applied in the SUSTAIN programme for
subcutaneous semaglutide.
Novo Nordisk is a global healthcare company with 95 years of innovation and leadership in diabetes care.
This heritage has given us experience and capabilities that also enable us to help people defeat obesity,
haemophilia, growth disorders and other serious chronic diseases. Headquartered in Denmark, Novo
Nordisk employs approximately 42,700 people in 79 countries and markets its products in more than 170
countries. Novo Nordisk's B shares are listed on Nasdaq Copenhagen (Novo-B). Its ADRs are listed on the
New York Stock Exchange (NVO). For more information, visit novonordisk.com, Facebook, Twitter,
LinkedIn, YouTube.
来源：诺和诺德官网
重磅！口服索马鲁肽第2项III期研究“头对头”击败恩格列净
诺和诺德5月29日宣布了口服索马鲁肽治疗2型糖尿病的第2项IIIa期研究（PIONEER 2）
的关键结果。
PIONEER 2是一项为期52周的开放标签、多中心、随机、平行分组、阳性对照研究，在
816例二甲双胍控制血糖不达标的患者中评估了每日1次口服索马鲁肽14mg和恩格列净25mg
的疗效和安全性差异 。主要终点是26周时HbA1c水平和体重较基线的变化，次要重点是52周
时HbA1c水平和体重较基线的变化。
PIONEER 2研究采用了两种显著不同的方法评估口服索马鲁肽的疗效：1）首要统计原则。
按照最新的监管指南，不管是否中止治疗并启用援救药物均纳入统计，评估口服索马鲁肽的疗
效。2）次要统计原则，只统计遵循治疗方案且未启用援救药物的患者，评估口服索马鲁肽的
疗效。
结果显示，按照首要统计原则，PIONEER 2研究达到主要终点，第26周时，口服索马鲁肽
降低HbA1c的作用显著优于恩格列净，但两组患者的体重减轻效果无显著差异。
若按照次要统计原则，口服索马鲁肽组患者第26周和第52周的HbA1c水平分别降低1.4%和
1.3%，恩格列净组分别为0.9%和0.8%。口服索马鲁肽组患者第26周和第52周的体重分别减轻
4.2和4.7kg，恩格列净组则在第26周和第52周均减重3.8kg。此外，第52周时口服索马鲁肽组
HbA1c水平低于7%的患者比例为72%，恩格列净组为47%。
研究中，口服索马鲁肽的耐受性良好，安全性数据与GLP-1疗法一致。最常见的不良反应
包括一过性的轻中度恶心。 PIONEER 2研究中，口服索马鲁肽组恶心发生率为20%。因为不良
反应中止治疗的患者比例为11%，恩格列净组为4%。
就在今年2月22日，诺和诺德公布了口服索马鲁肽PIONEER项目的第1项III期研究的结果，
在703例2型糖尿病患者中证明口服索马鲁肽3， 7， 14mg相比安慰剂降糖和减重效果明显。
口服索马鲁肽的PIONEER大型临床项目计划开展10项III期研究，计划招募8845例患者，
全部将在2018年内完成。
索马鲁肽是长效GLP-1受体激动剂，每周1次的索马鲁肽0.5mg、1mg预充注射笔
（Ozempic) 在2017年12月5日获得FDA批准，用于辅助饮食控制和运动以改善2型糖尿病患者
的血糖控制，2018年2月9日被EMA批准上市，2月21日被纳入Express Scripts的2018处方集，
开始与礼来的度拉糖肽正面交锋。分析师预测Ozempic的2022年销售额可达到22亿美元。
诺和诺德计划2019年提交口服索马鲁肽的上市申请，预期2020年获得批准上市。分析师
预测口服索马鲁肽的2022年销售额可达8.4亿美元，2025年可达到15亿美元。
来源：医药魔方