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Trial · Interventional

CompletedPhase 3Results postedRegistry data

Efficacy and Safety of Semaglutide Versus Canagliflozin as add-on to Metformin in Subjects With Type 2 Diabetes

Short name SUSTAIN 8

NCTNCT03136484 (opens ClinicalTrials.gov in a new tab)Other idNN9535-4270Other id2016-000989-35Other idU1111-1180-3651Other id2016
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
788 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
12 countries

United States, Argentina, Brazil, Canada, India, Ireland, Italy, Lebanon, Malaysia, Mexico, Sweden, United Kingdom

Start
15 Mar 2017
Primary completion
16 Oct 2018
Completion
16 Nov 2018
First posted
2 May 2017
Last update posted
21 Jan 2020
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
201720182019
  1. Ph 3

    SUSTAIN 8

    NCT03136484

    15 Mar 2017 to 16 Nov 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

This trial is conducted in Africa, Asia, Europe, North and South America. The aim of the trial is to compare the effect of once-weekly (OW) dosing of subcutaneous semaglutide (1.0 mg) versus once-daily dosing of oral canagliflozin (300 mg) on glycaemic control in subjects with type 2 diabetes (T2D) on a background treatment of metformin

Interventions

  • SemaglutideDrug
  • CanagliflozinDrug
  • Placebo (canagliflozin)Drug
  • Placebo (semaglutide)Drug

Arms2

  • Experimental

    Semaglutide + canagliflozin placebo

  • Active comparator

    Canagliflozin + semaglutide placebo

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in HbA1c

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in HbA1c (glycosylated haemoglobin) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first; and 'In-trial' observation period which started at the date of randomisation and include the period after initiation of rescue medication and/or premature trial product discontinuation, if any and ended at the last contact, withdrawal of consent or death, whichever came first.

Secondary outcomes(20)

  1. Change in Body Weight (kg)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  2. Change in Total Fat Mass (kg)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  3. Change in FPG (Fasting Plasma Glucose)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  4. Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in SMPG- mean 7-point profile was evaluated. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  5. Change in SMPG- Mean Postprandial Increment Over All Meals

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in SMPG- mean postprandial increment over all meals was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  6. Change in Fasting Total Cholesterol

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in fasting total cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  7. Change in Fasting LDL-cholesterol

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in fasting low-density lipoprotein (LDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  8. Change in Fasting HDL-cholesterol

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in fasting high-density lipoprotein (HDL) cholesterol (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  9. Change in Fasting Triglycerides

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in fasting triglycerides (mmol/L) is presented as ratio to baseline. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  10. Change in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in systolic blood pressure and diastolic blood pressure. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  11. Percentage Change in Body Weight (%)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in body weight was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  12. Change in Body Mass Index (BMI)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  13. Change in Waist Circumference

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in waist circumference was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  14. Percentage Change in Total Fat Mass (%)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in total fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  15. Change in Total Lean Mass (kg)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  16. Percentage Change in Total Lean Mass (%)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  17. Change in Visceral Fat Mass (kg)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  18. Percentage Change in Visceral Fat Mass (%)

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in visceral fat mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  19. Change in Ratio Between Total Fat Mass and Total Lean Mass

    Time frame · Week 0, week 52

    Registry description

    Change from baseline (week 0) to week 52 in ratio between total fat mass and total lean mass was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

  20. Participants Who Achieved HbA1c < 7.0% (53 mmol/Mol), American Diabetes Association (ADA) Target (Yes/no)

    Time frame · Week 52

    Registry description

    Percentage of participants who achieved HbA1c \< 7.0% (53 millimoles per mole \[mmol/mol\]), ADA target (yes/no) is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose to either the day of last dose plus 7 days or first initiation of rescue medication, whichever came first.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Week 0, week 52

Change in HbA1c

GroupValue (Percentage (%) of HbA1c)Spread
Semaglutide + Canagliflozin Placebo-1.71.1
Canagliflozin + Semaglutide Placebo-1.01.0
Secondary and other outcome results(7)
Secondary outcomeMean· Week 0, week 52

Change in Body Weight (kg)

GroupValue (Kilogram (kg))Spread
Semaglutide + Canagliflozin Placebo-5.75.4
Canagliflozin + Semaglutide Placebo-4.34.0
Secondary outcomeMean· Week 0, week 52

Change in Total Fat Mass (kg)

GroupValue (kg)Spread
Semaglutide + Canagliflozin Placebo-3.724.50
Canagliflozin + Semaglutide Placebo-2.633.30
Secondary outcomeMean· Week 0, week 52

Change in FPG (Fasting Plasma Glucose)

GroupValue (Millimoles per liter (mmol/L))Spread
Semaglutide + Canagliflozin Placebo-2.542.77
Canagliflozin + Semaglutide Placebo-2.002.53
Secondary outcomeMean· Week 0, week 52

Change in SMPG (Self-measured Plasma Glucose)- Mean 7-point Profile

GroupValue (mmol/L)Spread
Semaglutide + Canagliflozin Placebo-2.82.3
Canagliflozin + Semaglutide Placebo-1.92.7
Secondary outcomeMean· Week 0, week 52

Change in SMPG- Mean Postprandial Increment Over All Meals

GroupValue (mmol/L)Spread
Semaglutide + Canagliflozin Placebo-0.62.1
Canagliflozin + Semaglutide Placebo-0.62.0
Secondary outcomeGeometric mean· Week 0, week 52

Change in Fasting Total Cholesterol

GroupValue (Ratio of total cholesterol)Spread
Semaglutide + Canagliflozin Placebo0.9619.3
Canagliflozin + Semaglutide Placebo1.0318.2
Secondary outcomeGeometric mean· Week 0, week 52

Change in Fasting LDL-cholesterol

GroupValue (Ratio of LDL-cholesterol)Spread
Semaglutide + Canagliflozin Placebo0.9632.2
Canagliflozin + Semaglutide Placebo1.0529.0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
Semaglutide + Canagliflozin PlaceboParticipants received s.c. injection of semaglutide once-weekly for 52 weeks: 0.25 milligrams (mg) during 0-4 weeks followed by 0.5 mg during 5-8 weeks and then 1.0 mg during 9-52 weeks. Participants also received placebo matched to canagliflozin tablet once-daily for 52 weeks.1 / 39218 / 392185 / 392
Canagliflozin + Semaglutide PlaceboParticipants received canagliflozin tablet once-daily orally for 52 weeks: 100 mg tablet during 0-8 weeks followed by 300 mg tablet during 9-52 weeks. Participants also received placebo matched to semaglutide s.c. injection once-weekly for 52 weeks.0 / 39421 / 394120 / 394

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

Studies5

Studies that cite this trial.

Studies with results

4 studies on this page

Indexing hint: Meta-analysis (pooled) · 2025

15 results

Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes.

Natale et al. 2025The Cochrane database of systematic reviewscited by 8

PMID 39963952PMC11834151DOI 10.1002/14651858.cd015849.pub2PUB-39963952

Rights unknown15 results
Source linkSee results (15)

Indexing hint: Randomized controlled trial · 2020

5 results

Effects of once-weekly semaglutide vs once-daily canagliflozin on body composition in type 2 diabetes: a substudy of the SUSTAIN 8 randomised controlled clinical trial.

McCrimmon et al. 2020Diabetologiacited by 153

PMID 31897524PMC6997246DOI 10.1007/s00125-019-05065-8PUB-31897524

CC BY5 results
Download PDFSee results (5)

Indexing hint: Meta-analysis (pooled) · 2020

4 results

Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis.

Lingvay et al. 2020The Journal of clinical endocrinology and metabolismcited by 19

PMID 32827435PMC7549924DOI 10.1210/clinem/dgaa577PUB-32827435

CC BY4 results
Download PDFSee results (4)

Indexing hint: Randomized controlled trial · 2019

5 results

Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial.

Lingvay et al. 2019The lancet. Diabetes & endocrinologycited by 233

PMID 31540867DOI 10.1016/s2213-8587(19)30311-0PUB-31540867

Rights unknown5 results
Source linkSee results (5)

More studies

1 study on this page

PubMed tag: none · 2023

Cost-Effectiveness of Semaglutide vs. Empagliflozin, Canagliflozin, and Sitagliptin for Treatment of Patients with Type 2 Diabetes in Denmark: A Decision-Analytic Modelling Study.

Pulleyblank et al. 2023PharmacoEconomics - opencited by 1

PMID 37178435PMC10333151DOI 10.1007/s41669-023-00416-zPUB-37178435

Free to read · publisher termsCC BY-NC
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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 above18 years at the time of signing informed consent - Diagnosed with type 2 diabetes mellitus (T2D) - HbA1c of 7.0-10.5% (53-91 mmol/mol, both inclusive) - Stable daily dose of metformin (equal to or above1500 mg or maximum tolerated dose as documented in the subject medical record and in compliance with current local label) for at least 90 days prior to the day of screening Exclusion Criteria: - Known or suspected hypersensitivity to trial product(s) or related products - Previous participation in this trial. Participation is defined as signed informed consent - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice) - Participation in any clinical trial of an approved or non-approved investigational medicinal product within 90 days prior to the day of screening - Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol - Subject with alanine aminotransferase (ALT) above 2.5 x upper normal limit (UNL) - Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative - History or presence of pancreatitis (acute or chronic) - History of diabetic ketoacidosis (DKA) - Any of the following: myocardial infarction (MI), stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening - Subjects presently classified as being in New York Heart Association (NYHA) Class IV - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening - Renal impairment measured as eGFR below 60 ml/min/1.73 m\^2 as defined by Kidney Disease Improving global outcomes (KDIGO 2012) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening - Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed - Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within the past 90 days prior to randomisation - Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed - Medical history of diabetes-related lower limb amputations or signs of critical lower limb ischemia, (e.g. skin ulcer, osteomyelitis, or gangrene) within the last 26 weeks prior to screening

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