Clinical trial NCT03061214: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes (SUSTAIN - CHINA MRCT)
Official title: Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes. A 30-week Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multi-centre and Multi-national Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 868
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted in Africa, Asia, Europe and South America. The aim of the trial is to compare the effect of once-weekly dosing of two dose levels of semaglutide versus sitagliptin 100 mg once-daily on glycaemic control after 30 weeks of treatment. Subjects will remain on their stable pre-trial metformin.


Eligibility criteria: Inclusion Criteria: - Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male or female, age equal to or above 18 years at the time of signing informed consent - Subjects diagnosed with type 2 diabetes and on stable treatment in a period of 60 days prior to screening with metformin equal to or above 1500 mg (or maximum tolerated dose equal to or above 1000 mg). Stable is defined as unchanged medication and unchanged daily dose - HbA1c 7.0 - 10.5 % (53-91 mmol/mol) (both inclusive) Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential not using an adequate contraceptive method throughout the trial including the 5 week follow-up period (adequate contraceptive measure as required by local regulation or practice) - Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 60 days before screening. An exception is short-term treatment (equal to or below 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 ml/min/1.73 m\^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association (NYHA) class IV

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 30
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Week 0, week 30
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 30
measure: Change in Self-measured Plasma Glucose (SMPG) - Mean 7-point Profile
timeFrame: Week 0, week 30
measure: Change in Self-measured Plasma Glucose (SMPG) - Mean Postprandial Increment Over All Meals
timeFrame: Week 0, week 30
measure: Change in Fasting Insulin - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting C-peptide - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting Glucagon - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting Proinsulin - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting Proinsulin/Insulin Ratio - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting HOMA-B (Beta-cell Function) - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting HOMA-IR (Insulin Resistence) - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Patient Reported Outcome Questionnaire: SF-36v2™ Score
timeFrame: Week 0, week 30
measure: Change in Patient Reported Outcome Questionnaire: DTSQs Score
timeFrame: Week 0, week 30
measure: Change in High-sensitivity CRP - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Waist Circumference
timeFrame: Week 0, week 30
measure: Change in BMI
timeFrame: Week 0, week 30
measure: Change in Fasting Total Cholesterol - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting LDL Cholesterol - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting VLDL Cholesterol - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting HDL Cholesterol - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Fasting Triglycerides - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Free Fatty Acids - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
timeFrame: Week 0, week 30
measure: Percentage of Participants Who Achieved HbA1c <7.0% (53 mmol/Mol), ADA Target, (Yes/no)
timeFrame: Week 30
measure: Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/Mol), AACE Target, (Yes/no)
timeFrame: Week 30
measure: Percentage of Participants That Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol) Without Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemia and no Weight Gain
timeFrame: Week 30
measure: Percentage of Participants That Achieved (Yes/no): Body Weight Loss ≥5%
timeFrame: Week 30
measure: Percentage of Participants That Achieved (Yes/no): Body Weight Loss ≥10%
timeFrame: Week 30
measure: Total Number of Treatment Emergent Adverse Events
timeFrame: Week 0 to week 30
measure: Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Week 0 to week 30
measure: Participants With Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Week 0 to week 30
measure: Change in Haematological Parameter: Haemoglobin - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Haematological Parameter: Haematocrit - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter: Thrombocytes - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter: Erythrocytes - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter: Leukocytes - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter (Differential Cell Count of Leukocytes): Basophils - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter (Differential Cell Count of Leukocytes): Neutrophils - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter (Differential Cell Count of Leukocytes): Eosinophils - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter (Differential Cell Count of Leukocytes): Monocytes - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Hematological Parameter (Differential Cell Count of Leukocytes): Lymphocytes - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Amylase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Lipase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Alkaline Phosphatase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Alanine Aminotransferase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Aspartate Aminotransferase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Total Bilirubin - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Calcium (Corrected)- Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Total Calcium - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Potassium - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Sodium - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Albumin - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Creatine Kinase - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Total Protein- Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Creatinine - Ratio to Baseline
timeFrame: Week -2, week 30
measure: Change in Biochemistry Parameter: Urea - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Biochemistry Parameter: Estimated Glomerular Filtration Rate (eGFR) - Ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Calcitonin - Ratio to Baseline
timeFrame: Week -2, week 30
measure: Change in Urinalysis Parameter - UACR-ratio to Baseline
timeFrame: Week 0, week 30
measure: Change in Urinalysis Parameter: Glucose
timeFrame: Week 0, week 30
measure: Change in Urinalysis Parameter: pH
timeFrame: Week 0, week 30
measure: Change in Urinalysis Parameter: Protein
timeFrame: Week 0, week 30
measure: Change in Urinalysis Parameter: Ketones
timeFrame: Week 0, week 30
measure: Change in Urinalysis Parameter: Erythrocytes
timeFrame: Week 0, week 30
measure: Change in Clinical Evaluation: Pulse
timeFrame: Week 0, week 30
measure: Change in Clinical Evaluation: ECG
timeFrame: Week 0, week 30
measure: Change in Clinical Evaluation: Eye Examinations
timeFrame: Week 0, week 30
measure: Change in Physical Examination
timeFrame: Week -2, week 30
measure: Anti-semaglutide Antibody Levels
timeFrame: week 30, week 35
measure: Occurence of Anti-semaglutide Antibodies (Yes/no)
timeFrame: Week 0, week 16, week 30, week 35
measure: Occurence of Anti-semaglutide Antibodies With In-vitro Neutralising Effect (Yes/no)
timeFrame: Week 0, week 16, week 30, week 35
measure: Occurence of Anti-semaglutide Antibodies Cross Reacting With Endogenous GLP-1 (Yes/no)
timeFrame: Week 35
measure: Occurence of Cross Reacting Antibodies With in Vitro Neutralising Effect to Endogenous GLP-1 (Yes/no)
timeFrame: Week 35
Other outcomes:
Locations:
city: Aparecida de Goiania
country: Brazil
facility: Novo Nordisk Investigational Site
state: Goias
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Hefei
country: China
facility: Novo Nordisk Investigational Site
state: Anhui
city: Hefei
country: China
facility: Novo Nordisk Investigational Site
state: Anhui
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
state: Beijing
city: ChongQing
country: China
facility: Novo Nordisk Investigational Site
state: Chongqing
city: Fuzhou
country: China
facility: Novo Nordisk Investigational Site
state: Fujian
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guangzhou
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Zhuhai
country: China
facility: Novo Nordisk Investigational Site
state: Guangdong
city: Guiyang
country: China
facility: Novo Nordisk Investigational Site
state: Guizhou
city: Qiqihar
country: China
facility: Novo Nordisk Investigational Site
state: Heilongjiang
city: Chenzhou
country: China
facility: Novo Nordisk Investigational Site
state: Hunan
city: Changzhou
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanjing
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Suzhou
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Zhenjiang
country: China
facility: Novo Nordisk Investigational Site
state: Jiangsu
city: Nanchang
country: China
facility: Novo Nordisk Investigational Site
state: Jiangxi
city: Changchun
country: China
facility: Novo Nordisk Investigational Site
state: Jilin
city: Changchun
country: China
facility: Novo Nordisk Investigational Site
state: Jilin
city: Yanji
country: China
facility: Novo Nordisk Investigational Site
state: Jilin
city: Shenyang
country: China
facility: Novo Nordisk Investigational Site
state: Liaoning
city: Yinchuan
country: China
facility: Novo Nordisk Investigational Site
state: Ningxia
city: Xi'an
country: China
facility: Novo Nordisk Investigational Site
state: Shaanxi
city: Jinan
country: China
facility: Novo Nordisk Investigational Site
state: Shandong
city: Qingdao
country: China
facility: Novo Nordisk Investigational Site
state: Shandong
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Shanghai
country: China
facility: Novo Nordisk Investigational Site
state: Shanghai
city: Taiyuan
country: China
facility: Novo Nordisk Investigational Site
state: Shanxi
city: Tianjin
country: China
facility: Novo Nordisk Investigational Site
state: Tianjin
city: Kunming
country: China
facility: Novo Nordisk Investigational Site
state: Yunnan
city: Beijing
country: China
facility: Novo Nordisk Investigational Site
city: Changsha
country: China
facility: Novo Nordisk Investigational Site
city: Shatin, New Territories
country: Hong Kong
facility: Novo Nordisk Investigational Site
city: Daejeon
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Seoul
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Suwon-si, Gyeonggi-do
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Suwon
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Wonju
country: Korea, Republic of
facility: Novo Nordisk Investigational Site
city: Boksburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Johannesburg
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Pretoria
country: South Africa
facility: Novo Nordisk Investigational Site
state: Gauteng
city: Durban
country: South Africa
facility: Novo Nordisk Investigational Site
state: KwaZulu-Natal
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taipei
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Taoyuan city
country: Taiwan
facility: Novo Nordisk Investigational Site
city: Dnipro
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Kyiv
country: Ukraine
facility: Novo Nordisk Investigational Site
city: Lviv
country: Ukraine
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Ji L, Dong X, Li Y, Li Y, Lim S, Liu M, Ning Z, Rasmussen S, Skjoth TV, Yuan G, Eliaschewitz FG. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as add-on to metformin in patients with type 2 diabetes in SUSTAIN China: A 30-week, double-blind, phase 3a, randomized trial. Diabetes Obes Metab. 2021 Feb;23(2):404-414. doi: 10.1111/dom.14232. Epub 2021 Jan 3.