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NCT02305381: SUSTAIN™ 5

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to Basal Insulin Alone or Basal Insulin in Combination With Metformin in Subjects With Type 2 Diabetes

Completed Phase 3 Results posted Last updated 11 June 2019
What this trial tests

Phase 3 trial testing semaglutide in Diabetes in 397 participants. Completed in 21 November 2015.

Timeline
1 December 2014
Primary endpoint
21 November 2015
21 November 2015

Quick facts

Lead sponsorNovo Nordisk A/S
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment397
Start date1 December 2014
Primary completion21 November 2015
Estimated completion21 November 2015
Sites99 locations across Japan, Slovakia, Serbia, Germany, Puerto Rico, United States

Drugs / interventions tested

Conditions studied

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Diabetes or Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in HbA1c (Glycosylated Haemoglobin) Primary · Week 0, week 30

Estimated mean change from baseline in HbA1c at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

GroupValue95% CI
Semaglutide 0.5 mg-1.45± 0.09
Semaglutide 1.0 mg-1.85± 0.09
Placebo-0.09± 0.09
Change in Body Weight Secondary · Week 0, week 30

Estimated mean change from baseline in body weight at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

GroupValue95% CI
Semaglutide 0.5 mg-3.67± 0.36
Semaglutide 1.0 mg-6.42± 0.36
Placebo-1.36± 0.37
Change in Fasting Plasma Glucose (FPG) Secondary · week 0, week 30

Estimated mean change from baseline in FPG at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

GroupValue95% CI
Semaglutide 0.5 mg-29.14± 3.74
Semaglutide 1.0 mg-42.38± 3.76
Placebo-8.51± 4.02
Change in Insulin Dose Secondary · week 0, week 30

Estimated mean change from baseline in insulin dose at week 30 was measured in terms of ratio to baseline. Responses at week 30 are analysed using an Analysis of covariance model with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using last observation carried forward.

GroupValue95% CI
Semaglutide 0.5 mg0.90± 0.01
Semaglutide 1.0 mg0.85± 0.01
Placebo0.96± 0.01
Change in Systolic and Diastolic Blood Pressure Secondary · week 0, week 30

Estimated mean change from baseline in systolic and diastolic blood pressure at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.

Diastolic blood pressure
GroupValue95% CI
Semaglutide 0.5 mg-1.84± 0.73
Semaglutide 1.0 mg-1.50± 0.74
Placebo-2.17± 0.79
Systolic blood pressure
GroupValue95% CI
Semaglutide 0.5 mg-4.29± 1.26
Semaglutide 1.0 mg-7.27± 1.27
Placebo-0.99± 1.34
Patient Reported Outcomes, Diabetes Treatment Satisfaction Questionnaire (DTSQ) Secondary · week 0, week 30

The DTSQs questionnaire was used to assess subjects' treatment satisfaction and contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. The post-baseline responses are analysed us

GroupValue95% CI
Semaglutide 0.5 mg2.73± 0.46
Semaglutide 1.0 mg3.47± 0.46
Placebo1.25± 0.50
HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association (ADA) Target Secondary · After 30 weeks treatment

Percentage of subjects with HbA1C below 7.0% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.

GroupValue95% CI
Semaglutide 0.5 mg60.6
Semaglutide 1.0 mg78.6
Placebo10.5
HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target Secondary · After 30 weeks treatment

Percentage of participants with HbA1c below or equal to 6.5% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening \[\<= 8.0% or \> 8.0%\] crossed with use of metformin \[yes or no\]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.

GroupValue95% CI
Semaglutide 0.5 mg40.9
Semaglutide 1.0 mg61.1
Placebo4.5

Adverse events — posted to ClinicalTrials.gov

Time frame: From the first dose of trial product until the end of the post-treatment follow-up period.The follow-up visit was scheduled to take place 5 weeks after the date of last dose of trial product with a visit window of +7 days (maximum 36 weeks).. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide 0.5 mg
Serious: 8/132 (6%)
Deaths:
Semaglutide 1.0 mg
Serious: 12/131 (9%)
Deaths:
Placebo
Serious: 9/133 (7%)
Deaths:

Serious adverse events (37 terms)

ReactionSystemSemaglutide 0.5 mgSemaglutide 1.0 mgPlacebo
Acute coronary syndromeCardiac disorders
AnaemiaBlood and lymphatic system disorders
Back painMusculoskeletal and connective tissue disorders
Blood pressure increasedInvestigations
BronchitisInfections and infestations
Cardiac failureCardiac disorders
Carotid artery stenosisNervous system disorders
Carotid endarterectomySurgical and medical procedures
CataractEye disorders
Cholecystitis acuteHepatobiliary disorders
Clostridium difficile colitisInfections and infestations
Coronary arterial stent insertionSurgical and medical procedures
Coronary artery bypassSurgical and medical procedures
Coronary artery diseaseCardiac disorders
DepressionPsychiatric disorders
Diabetes mellitus inadequate controlMetabolism and nutrition disorders
DiverticulitisInfections and infestations
Drug hypersensitivityImmune system disorders
Femoral artery occlusionVascular disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
HypoglycaemiaMetabolism and nutrition disorders
Hypoglycaemic unconsciousnessNervous system disorders
Ischaemic strokeNervous system disorders
Lumbar spinal stenosisMusculoskeletal and connective tissue disorders
Meningitis asepticInfections and infestations
Other adverse events (8 terms — click to expand)

ReactionSystemSemaglutide 0.5 mgSemaglutide 1.0 mgPlacebo
NauseaGastrointestinal disorders
VomitingGastrointestinal disorders
NasopharyngitisInfections and infestations
Lipase increasedInvestigations
DiarrhoeaGastrointestinal disorders
Upper respiratory tract infectionInfections and infestations
Urinary tract infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders

Most-reported serious reactions: Acute coronary syndrome, Anaemia, Back pain, Blood pressure increased, Bronchitis, Cardiac failure, Carotid artery stenosis, Carotid endarterectomy.

Data from ClinicalTrials.gov NCT02305381 adverse events section.

Sponsor's own description

This trial is conducted in Asia, Europe and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of semaglutide once weekly versus placebo as add-on to basal insulin alone or basal insulin in combination with metformin in subjects with type 2 diabetes.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial.
    Rodbard HW, Lingvay I, Reed J, de la Rosa R, et al · · 2018 · cited 273× · PMID 29688502 · DOI 10.1210/jc.2018-00070
  2. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.
    Husain M, Bain SC, Jeppesen OK, Lingvay I, et al · · 2020 · cited 144× · PMID 31903692 · DOI 10.1111/dom.13955
  3. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials.
    Ahrén B, Atkin SL, Charpentier G, Warren ML, et al · · 2018 · cited 98× · PMID 29766634 · DOI 10.1111/dom.13353
  4. Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes.
    Mahapatra MK, Karuppasamy M, Sahoo BM. · · 2022 · cited 92× · PMID 34993760 · DOI 10.1007/s11154-021-09699-1
  5. Therapeutic Potential of Semaglutide, a Newer GLP-1 Receptor Agonist, in Abating Obesity, Non-Alcoholic Steatohepatitis and Neurodegenerative diseases: A Narrative Review.
    Mahapatra MK, Karuppasamy M, Sahoo BM. · · 2022 · cited 84× · PMID 35650449 · DOI 10.1007/s11095-022-03302-1
  6. Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials.
    Karagiannis T, Malandris K, Avgerinos I, Stamati A, et al · · 2024 · cited 64× · PMID 38613667 · DOI 10.1007/s00125-024-06144-1
  7. 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 M, Bain SC, Holst AG, Mark T, et al · · 2020 · cited 29× · PMID 32998732 · DOI 10.1186/s12933-020-01106-4
  8. Impact of baseline characteristics and beta-cell function on the efficacy and safety of subcutaneous once-weekly semaglutide: A patient-level, pooled analysis of the SUSTAIN 1-5 trials.
    Aroda VR, Capehorn MS, Chaykin L, Frias JP, et al · · 2020 · cited 21× · PMID 31608552 · DOI 10.1111/dom.13896

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02305381.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing