Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial

医学 耐受性 2型糖尿病 安慰剂 临床终点 糖尿病 内科学 体质指数 随机对照试验 不利影响 内分泌学 替代医学 病理
作者
Julio Rosenstock,Carol Wysham,Juan P. Frías,Shizuka Kaneko,Clare J. Lee,Laura Fernández Landó,Huzhang Mao,Xuewei Cui,Chrisanthi A. Karanikas,Vivian T. Thieu
出处
期刊:The Lancet [Elsevier BV]
卷期号:398 (10295): 143-155 被引量:690
标识
DOI:10.1016/s0140-6736(21)01324-6
摘要

Background Despite advancements in care, many people with type 2 diabetes do not meet treatment goals; thus, development of new therapies is needed. We aimed to assess efficacy, safety, and tolerability of novel dual glucose-dependent insulinotropic polypeptide and GLP-1 receptor agonist tirzepatide monotherapy versus placebo in people with type 2 diabetes inadequately controlled by diet and exercise alone. Methods We did a 40-week, double-blind, randomised, placebo-controlled, phase 3 trial (SURPASS-1), at 52 medical research centres and hospitals in India, Japan, Mexico, and the USA. Adult participants (≥18 years) were included if they had type 2 diabetes inadequately controlled by diet and exercise alone and if they were naive to injectable diabetes therapy. Participants were randomly assigned (1:1:1:1) via computer-generated random sequence to once a week tirzepatide (5, 10, or 15 mg), or placebo. All participants, investigators, and the sponsor were masked to treatment assignment. The primary endpoint was the mean change in glycated haemoglobin (HbA1c) from baseline at 40 weeks. This study is registered with ClinicalTrials.gov, NCT03954834. Findings From June 3, 2019, to Oct 28, 2020, of 705 individuals assessed for eligibility, 478 (mean baseline HbA1c 7·9% [63 mmol/mol], age 54·1 years [SD 11·9], 231 [48%] women, diabetes duration 4·7 years, and body-mass index 31·9 kg/m2) were randomly assigned to tirzepatide 5 mg (n=121 [25%]), tirzepatide 10 mg (n=121 [25%]), tirzepatide 15 mg (n=121 [25%]), or placebo (n=115 [24%]). 66 (14%) participants discontinued the study drug and 50 (10%) discontinued the study prematurely. At 40 weeks, all tirzepatide doses were superior to placebo for changes from baseline in HbA1c, fasting serum glucose, bodyweight, and HbA1c targets of less than 7·0% (<53 mmol/mol) and less than 5·7% (<39 mmol/mol). Mean HbA1c decreased from baseline by 1·87% (20 mmol/mol) with tirzepatide 5 mg, 1·89% (21 mmol/mol) with tirzepatide 10 mg, and 2·07% (23 mmol/mol) with tirzepatide 15 mg versus +0·04% with placebo (+0·4 mmol/mol), resulting in estimated treatment differences versus placebo of −1·91% (−21 mmol/mol) with tirzepatide 5 mg, −1·93% (−21 mmol/mol) with tirzepatide 10 mg, and −2·11% (−23 mmol/mol) with tirzepatide 15 mg (all p<0·0001). More participants on tirzepatide than on placebo met HbA1c targets of less than 7·0% (<53 mmol/mol; 87–92% vs 20%) and 6·5% or less (≤48 mmol/mol; 81–86% vs 10%) and 31–52% of patients on tirzepatide versus 1% on placebo reached an HbA1c of less than 5·7% (<39 mmol/mol). Tirzepatide induced a dose-dependent bodyweight loss ranging from 7·0 to 9·5 kg. The most frequent adverse events with tirzepatide were mild to moderate and transient gastrointestinal events, including nausea (12–18% vs 6%), diarrhoea (12–14% vs 8%), and vomiting (2–6% vs 2%). No clinically significant (<54 mg/dL [<3 mmol/L]) or severe hypoglycaemia were reported with tirzepatide. One death occurred in the placebo group. Interpretation Tirzepatide showed robust improvements in glycaemic control and bodyweight, without increased risk of hypoglycaemia. The safety profile was consistent with GLP-1 receptor agonists, indicating a potential monotherapy use of tirzepatide for type 2 diabetes treatment. Funding Eli Lilly and Company.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
文艺涵菡完成签到,获得积分20
刚刚
舒心的冷安完成签到,获得积分10
刚刚
WHR完成签到,获得积分10
1秒前
又欠粥了发布了新的文献求助10
1秒前
yemma完成签到,获得积分10
2秒前
o30发布了新的文献求助10
2秒前
和谐乌冬面完成签到,获得积分10
2秒前
2秒前
ky一下发布了新的文献求助10
3秒前
思源应助Grace采纳,获得30
3秒前
3秒前
wanci应助无聊的小蚂蚁采纳,获得10
4秒前
Orange应助典雅的俊驰采纳,获得10
4秒前
4秒前
5秒前
5秒前
派大星完成签到,获得积分10
5秒前
funny完成签到,获得积分10
5秒前
5秒前
6秒前
7秒前
打打应助o30采纳,获得10
7秒前
7秒前
7秒前
night发布了新的文献求助10
8秒前
林小乌龟完成签到,获得积分10
8秒前
8秒前
9秒前
9秒前
9秒前
9秒前
yznfly应助djbj2022采纳,获得30
9秒前
9秒前
风雨琳琅完成签到,获得积分10
10秒前
Hello应助daidaimumu采纳,获得10
10秒前
赘婿应助li采纳,获得10
10秒前
balabalabala完成签到,获得积分10
11秒前
abocide完成签到,获得积分10
11秒前
司空元正发布了新的文献求助10
11秒前
Baneyhua发布了新的文献求助10
11秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969335
求助须知:如何正确求助?哪些是违规求助? 3514162
关于积分的说明 11172430
捐赠科研通 3249456
什么是DOI,文献DOI怎么找? 1794853
邀请新用户注册赠送积分活动 875437
科研通“疑难数据库(出版商)”最低求助积分说明 804809