Primary outcomeNumber· Weeks 0-56
Number of Treatment Emergent Adverse Events (TEAEs)
| Group | Value (Number of events) |
|---|---|
| Semaglutide 0.5 mg | 909 |
| Semaglutide 1.0 mg | 954 |
| Additional OAD | 269 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataA Trial Comparing the Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes
Short name SUSTAIN™
NCTNCT02207374 (opens ClinicalTrials.gov in a new tab)Other idNN9535-4091Other idU1111-1140-3081Other idJapicCTI-142640
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 601 participants (actual)
- Sponsor
- Novo Nordisk A/S · Industry
- Design
- Randomized · Open label (no masking)
- Countries
1 country
Japan
- Start
- 4 Aug 2014
- Primary completion
- 27 Feb 2016
- Completion
- 27 Feb 2016
- First posted
- 4 Aug 2014 (estimated)
- Last update posted
- 7 Jan 2019
- Conditions
- Diabetes · Diabetes Mellitus, Type 2
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
2014201520162017
- Ph 3
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
This trial is conducted in Asia. The aim of the trial is to investigate safety and efficacy of semaglutide once weekly in monotherapy or in combination with one OAD (oral anti-diabetic drug) in Japanese subjects with type 2 diabetes who are insufficiently controlled on diet/exercise therapy or OAD monotherapy. All subjects will continue their pre-trial treatment (diet and exercise therapy or OAD monotherapy in addition to diet and exercise therapy) during the trial.
Interventions
- semaglutideDrug
- DPP-4 inhibitorDrug
Arms3
Experimental
Semaglutide 0.5 mg
Experimental
Semaglutide 1.0 mg
Active comparator
One additional OAD + pre-trial treatment
The type and dosage of the additional OAD will be selected by the investigators according to the approved Japanese labelling including drug combinations and contraindications. One of DPP-4 inhibitor (dipeptidyl peptidase-4), SU (sulfonylurea), glinide, biguanide, α-GI (α-glucosidase inhibitor)or TZD (thiazolidinediones) will be selected as the additional OAD. For the subjects treated with OAD monotherapy as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD should be chosen.
Primary outcomes1
Outcomes the sponsor listed as primary.
Number of Treatment Emergent Adverse Events (TEAEs)
Time frame · Weeks 0-56
Registry description
An adverse event (AEs) was defined as any unfavorable 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 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).
Secondary outcomes(2)
Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
Time frame · Weeks 0-56
Registry description
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 0-56 treatment period) and no later than the follow-up visit during the on-treatment observation period (date of last dose + 42 days).
Change in Glycosylated Haemoglobin A1c (HbA1c)
Time frame · Week 0, week 56
Registry description
The observed mean change in HbA1c values from baseline after 56 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.
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(2)
Secondary outcomeNumber· Weeks 0-56
Number of Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes
| Group | Value (Number of episodes) |
|---|---|
| Semaglutide 0.5 mg | 4 |
| Semaglutide 1.0 mg | 8 |
| Additional OAD | 2 |
Secondary outcomeLeast squares mean· Week 0, week 56
Change in Glycosylated Haemoglobin A1c (HbA1c)
| Group | Value (Percentage (%) of HbA1c) | Spread |
|---|---|---|
| Semaglutide 0.5 mg | -1.74 | 0.05 |
| Semaglutide 1.0 mg | -2.03 | 0.05 |
| Additional OAD | -0.67 | 0.07 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| Semaglutide 0.5 mgSubjects were randomized to receive semaglutide 0.5 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly 0.5 mg maintenance dose for 52 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial. | – | 19 / 239 | 160 / 239 |
| Semaglutide 1.0 mgSubjects were randomized to receive semaglutide 1.0 mg once weekly subcutaneously (s.c.; under the skin) in the thigh, abdomen, or upper arm for a period up to 56 weeks. The treatment period was divided into the dose escalation and the dose maintenance period. Subjects followed a fixed dose escalation pattern to mitigate tolerability concerns, starting with once-weekly doses of 0.25 mg for 4 weeks (4 doses), then escalated to once weekly doses of 0.5 mg for 4 weeks, and finally escalated to once weekly 1.0 mg maintenance dose for 48 weeks (maximum dose). Doses were not changed during the trial after the maintenance dose was reached. Semaglutide 1.34 mg/mL was supplied in a 1.5 mL pre-filled PDS290 pen-injector and administered on the same day of every week during the trial. All subjects continued their pre-trial treatment of either diet and exercise therapy or OAD monotherapy in addition to diet and exercise throughout the trial. | – | 12 / 241 | 169 / 241 |
| Additional OADSubjects were randomised to receive one additional OAD in addition to the pre-trial treatment for a duration of 56 weeks. The type and dosage of the additional OAD was selected by the investigator according to the approved Japanese labelling based on drug combinations and contraindications. One of the following OADs was to be selected as the additional OAD therapy: dipeptidyl peptidase-4 (DPP-4) inhibitor, SU, glinide, biguanide, α-GI and TZD. For subjects treated with OAD as pre-trial treatment, the type and dosage of the additional OAD with a different mechanism of action from the pre-trial OAD was to be chosen. The dose of the additional OAD was optimized within approved Japanese labelling until week 8 (dose adjustment period) and the dose remained unchanged until week 56 (maintenance dose) unless rescue medication was needed. The type of the additional OAD remained unchanged during the trial. | – | 8 / 120 | 61 / 120 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies4
Studies that cite this trial.
Studies with results
1 study on this page
Indexing hint: Randomized controlled trial · 2018
8 results
Safety and efficacy of once-weekly semaglutide vs additional oral antidiabetic drugs in Japanese people with inadequately controlled type 2 diabetes: A randomized trial.
Kaku et al. 2018Diabetes, obesity & metabolismcited by 106
PMID 29322610PMC5969242DOI 10.1111/dom.13218PUB-29322610
Free to read · publisher termsCC BY-NC8 results
More studies
3 studies on this page
PubMed tag: none · 2020
Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.
Husain et al. 2020Cardiovascular diabetologycited by 33
PMID 32998732PMC7526237DOI 10.1186/s12933-020-01106-4PUB-32998732
CC BY
PubMed tag: none · 2018
Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes.
Petri et al. 2018Diabetes, obesity & metabolismcited by 47
PMID 29748996PMC6099226DOI 10.1111/dom.13358PUB-29748996
Free to read · publisher termsCC BY-NC
PubMed tag: none · 2018
Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis.
Carlsson Petri et al. 2018Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 43
PMID 29907893PMC6064581DOI 10.1007/s13300-018-0458-5PUB-29907893
Free to read · publisher termsCC BY-NC
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 20 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* Male or female, age at least 20 years at the time of signing informed consent
* HbA1c (glycosylated haemoglobin A1c) between 7.0% and 10.5% (53-91 mmol/mol) (both inclusive)
* Japanese subjects with type 2 diabetes mellitus (diagnosed clinically) and on stable treatment (defined as unchanged medication and unchanged dose) who are: a) on diet and exercise therapy for at least 30 days before Visit 1 (week -2). or b) on OAD monotherapy (either of SU (sulfonylurea), glinide, a-GI (a-glucosidase inhibitor) or TZD (thiazolidinediones)) within approved Japanese labelling in addition to diet and exercise therapy for at least 60 days before Visit 1 (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 \[not having sex\], diaphragm, condom \[by the partner\], intrauterine device, sponge, spermicide or oral contraceptives) throughout the trial including the 5 week follow-up period
* Treatment with glucose lowering agent(s) other than stated in the inclusion criteria within 60 days before Visit 1 (week -2) and treatment with once weekly glucagon-like peptide-1 (GLP-1) receptor agonists within 90 days before Visit 1 (week -2). An exception is short-term treatment (below or equal to 7 days 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 above or equal to 50 ng/L (pg/mL)
* 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) below 30 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 (Visit 2 \[week 0\])
* Heart failure, New York Heart Association (NYHA) class IV
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