A Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily in Japanese Subjects With Type 2 Diabetes (SUSTAIN™)

• ClinicalTrials.gov Identifier: NCT02254291
• Recruitment Status: Completed
• First Posted: October 1, 2014
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

Study Description

Brief Summary:

This trial is conducted in Japan. The purpose is to compare the safety of once-weekly dosing of semaglutide (0.5 and 1.0 mg) versus sitagliptin (100 mg) once daily, both as monotherapy during 30 weeks of treatment in Japanese subjects with type 2 diabetes.

Condition or disease	Intervention/treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: semaglutide; Drug: sitagliptin	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 308 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily, Both as Monotherapy in Japanese Subjects With Type 2 Diabetes
• Actual Study Start Date: October 2, 2014
• Actual Primary Completion Date: November 11, 2015
• Actual Study Completion Date: November 11, 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Semaglutide 0.5 mg	Drug: semaglutide; Once weekly doses of 0.5 mg semaglutide after an initial dose escalation step of 0.25 mg (4 weeks). Total duration of treatment is 30 weeks. Administered subcutaneously (s.c. under the skin).
Experimental: Semaglutide 1.0 mg	Drug: semaglutide; Once weekly doses of 1.0 mg semaglutide after an initial dose escalation step of 0.25 mg (4 weeks) followed by 0.5 mg for 4 weeks. Total duration of treatment is 30 weeks. Administered subcutaneously (s.c. under the skin).
Active Comparator: Sitagliptin 100 mg	Drug: sitagliptin; Daily doses of 100 mg sitagliptin. Total duration of treatment is 30 weeks. Administered as oral tablets.

Outcome Measures

Primary Outcome Measures :

1. Number of Treatment Emergent Adverse Events (TEAEs) [ Time Frame: Weeks 0-30 ]
   An adverse events (AEs) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).

Secondary Outcome Measures :

1. Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes [ Time Frame: Weeks 0-30 ]
   Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe and/or BG confirmed by a plasma glucose value of <56 mg/dL (3.1 mmol/L), with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. The episodes mentioned here are treatment emergent hypoglycaemic episodes and defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment (week 0-30 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).
2. Change in Glycosylated Haemoglobin A1c (HbA1c) [ Time Frame: Week 0 and week 30 ]
   Mean changes in HbA1c values from baseline after 30 weeks of treatment. Changes in HbA1c were analysed using a mixed model for repeated measurements (MMRM) with treatment and pre-trial treatment at screening as fixed factors and baseline value as covariate. The data were analysed for the "on-treatment without rescue medication" observation period which includes observations noted at or after the date of first dose of randomised treatment and not after the last dose of the trial product (+ a 7-day visit window) or initiation of rescue medication.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Male or female, age 20 years or older at the time of signing informed consent
• Glycated hemoglobin (HbA1c) between 6.5% and 9.5% (48-80 mmol/mol) (both inclusive) for subjects treated with oral antidiabetic drug (OAD) monotherapy and between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive) for subjects treated with diet and exercise therapy at screening
• Japanese subjects diagnosed with type 2 diabetes who are: a) on stable OAD monotherapy at a half-maximum dose or below according to the approved Japanese labelling in addition to diet and exercise therapy for at least 30 days prior to screening (week -8) (For metformin only: the maximum dose of 750 mg/day is allowed except for METGLUCO®. For METGLUCO®, the allowable half-max dose of 1125 mg/day must be applied.). 'Stable' is defined as unchanged medication and unchanged dose, or b) on stable diet and exercise therapy for at least 30 days prior to screening (week -2)

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (e.g. abstinence, diaphragm, condom [by the partner], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5-week follow-up period
• Treatment with once-weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days prior to screening
• Treatment with any glucose lowering agent(s) (except for pre-trial OAD for subject treated with OAD monotherapy) in a period of 60 days prior to screening. An exception is short-term treatment (7 days or less in total) with insulin in connection with inter-current illness
• Any disorder which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol
• History of chronic or idiopathic acute pancreatitis
• Screening calcitonin value of 50 ng/L (pg/mL) or greater
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)
• Impaired renal function defined as estimated glomerular filtration rate (eGFR) less than 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

Contacts and Locations

Locations

Japan

Novo Nordisk Investigational Site

Asahikawa-shi, Hokkaido, Japan, 070 0002

Novo Nordisk Investigational Site

Chitose, Hokkaido, Japan, 066-0032

Novo Nordisk Investigational Site

Chuo-ku Tokyo, Japan, 103-0027

Novo Nordisk Investigational Site

Chuo-ku Tokyo, Japan, 104-0031

Novo Nordisk Investigational Site

Chuo-ku, Tokyo, Japan, 103 0027

Novo Nordisk Investigational Site

Ebina-shi, Japan, 243 0432

Novo Nordisk Investigational Site

Izumisano-shi, Japan, 598 0048

Novo Nordisk Investigational Site

Kashiwara-shi, Osaka, Japan, 582 0005

Novo Nordisk Investigational Site

Katsushika-ku, Tokyo, Japan, 125 0054

Novo Nordisk Investigational Site

Kumamoto-shi,Kumamoto, Japan, 862 0976

Novo Nordisk Investigational Site

Naka-shi, Ibaraki, Japan, 311 0113

Novo Nordisk Investigational Site

Nishinomiya-shi, Hygo, Japan, 662 0971

Novo Nordisk Investigational Site

Oita-shi, Japan, 870 0039

Novo Nordisk Investigational Site

Osaka-shi, Osaka, Japan, 553 0003

Novo Nordisk Investigational Site

Ota-ku, Tokyo, Japan, 144 0035

Novo Nordisk Investigational Site

Ota-ku, Tokyo, Japan

Novo Nordisk Investigational Site

Sapporo-shi, Hokkaido, Japan, 060 0062

Novo Nordisk Investigational Site

Sapporo-shi, Hokkaido, Japan, 060-0001

Novo Nordisk Investigational Site

Shimotsuke-shi, Tochigi, Japan, 329 0433

Novo Nordisk Investigational Site

Shinjuku-ku, Tokyo, Japan, 160-0008

Novo Nordisk Investigational Site

Suita-shi, Osaka, Japan, 565-0853

Novo Nordisk Investigational Site

Takatsuki-shi, Osaka, Japan, 569 1096

Novo Nordisk Investigational Site

Tokyo, Japan, 181-0013

Novo Nordisk Investigational Site

Yokohama, Kanagawa, Japan, 236-0004

Novo Nordisk Investigational Site

Yokohama-shi, Japan, 235 0045

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry GCR, 1452; Novo Nordisk A/S

More Information

Additional Information:

Clinical Trials at Novo Nordisk 

Publications of Results:

Seino Y, Terauchi Y, Osonoi T, Yabe D, Abe N, Nishida T, Zacho J, Kaneko S. Safety and efficacy of semaglutide once weekly vs sitagliptin once daily, both as monotherapy in Japanese people with type 2 diabetes. Diabetes Obes Metab. 2018 Feb;20(2):378-388. doi: 10.1111/dom.13082. Epub 2017 Oct 5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02254291
• Other Study ID Numbers: NN9535-4092; U1111-1140-5334 ( Other Identifier: WHO ); JapicCTI-142663 ( Registry Identifier: JAPIC )
• First Posted: October 1, 2014
• Results First Posted: September 13, 2018
• Last Update Posted: September 13, 2018
• Last Verified: December 2017

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 2; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Sitagliptin Phosphate; Hypoglycemic Agents; Physiological Effects of Drugs; Incretins; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Dipeptidyl-Peptidase IV Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action