NCT03191396: SUSTAIN 10

Research Study Comparing a New Medicine Semaglutide to Liraglutide in People With Type 2 Diabetes

Completed Phase 3 Results posted Last updated 15 October 2019

What this trial tests

Phase 3 trial testing Semaglutide in Diabetes in 577 participants. Completed in 13 August 2018.

Timeline

27 June 2017

Primary endpoint
9 July 2018

13 August 2018

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	577
Start date	27 June 2017
Primary completion	9 July 2018
Estimated completion	13 August 2018
Sites	92 locations across France, Italy, Finland, Sweden, United Kingdom, Germany, Hungary, Poland

Drugs / interventions tested

• Semaglutide (semaglutide) — full drug profile →
• Liraglutide (liraglutide) — full drug profile →

Conditions studied

• Diabetes — all drugs for Diabetes →
• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

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 Primary · Week 0, week 30

Mean change from baseline (week 0) to week 30 in glycosylated haemoglobin (HbA1c) %. The endpoint was evaluated based on the 'on-treatment without rescue medication period' where subjects were considered treated with trial product, but had not yet initiated rescue medication. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-1.7	± 0.9
Liraglutide 1.2 mg	-1.1	± 1.0

Change in Body Weight (kg) Secondary · Week 0, week 30

Mean change from baseline (week 0) to week 30 in body weight measured in kilograms. Results are based on the 'on-treatment without rescue medication' observation period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-5.8	± 4.7
Liraglutide 1.2 mg	-2.0	± 4.1

Change in Fasting Plasma Glucose (FPG) Secondary · Week 0, week 30

Mean change from baseline in fasting plasma glucose measured in mmol/L. Results are based on the 'on-treatment without rescue medication' observation period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-2.65	± 2.19
Liraglutide 1.2 mg	-1.46	± 2.42

Change in Self-measured Plasma Glucose (SMPG), 7 Point Profile: Mean 7-point Profile Secondary · Week 0, week 30

Mean change from baseline in 7-point profile. 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. The mean of the 7-point SMPG profile, defined as the area under the profile, was calculated using the trapezoidal method and divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period. Missing data were imputed using observed data from subjects within the same group defined by randomised

Group	Value	95% CI
Semaglutide 1.0 mg	-3.0	± 2.0
Liraglutide 1.2 mg	-2.1	± 2.3

Change in Self-measured Plasma Glucose (SMPG), 7 Point Profile: Mean Post Prandial Increment (Over All Meals) Secondary · Week 0, week 30

Mean post prandial glucose incrememts over all meals. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-1.0	± 1.8
Liraglutide 1.2 mg	-0.4	± 1.9

Change in Fasting Blood Lipids: Total Cholesterol Secondary · Week 0, week 30

The change from baseline in total cholesterol (measured in mmol/L) is presented as ratio to baseline. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	0.96	± 16.8
Liraglutide 1.2 mg	0.98	± 16.9

Change in Fasting Blood Lipids: Low-density Lipoprotein (LDL)-Cholesterol Secondary · Week 0, week 30

The change from baseline in LDL cholesterol is presented as ratio to baseline. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	0.99	± 28.3
Liraglutide 1.2 mg	0.99	± 27.2

Change in Fasting Blood Lipids: High-density Lipoprotein (HDL)-Cholesterol Secondary · Week 0, week 30

The change from baseline in HDL cholesterol is presented as ratio to baseline. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	1.01	± 14.6
Liraglutide 1.2 mg	0.99	± 12.9

Change in Fasting Blood Lipids: Triglycerides Secondary · Week 0, week 30

The change from baseline in triglycerides is presented as ratio to baseline. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	0.83	± 41.5
Liraglutide 1.2 mg	0.91	± 39.5

Change in Body Mass Index (BMI) Secondary · Week 0, week 30

Mean change from baseline (week 0) to week 30 in BMI. BMI was calculated as 'body weight in kg/(height in meters) x (height in meters)'. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-2.0	± 1.6
Liraglutide 1.2 mg	-0.7	± 1.4

Change in Waist Circumference Secondary · Week 0, week 30

Mean change in waist circumference (cm) from baseline (week 0) to week 30. Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-5.2	± 5.6
Liraglutide 1.2 mg	-2.4	± 4.6

Change in Systolic Blood Pressure Secondary · Week 0, week 30

Change in systolic blood pressure from baseline (week 0) to week 30 . Results are based on the on-treatment without rescue medication period. Missing data were imputed using observed data from subjects within the same group defined by randomised treatment, using a regression model including stratification factor as categorical effect and data from baseline and all previous visits as covariates.

Group	Value	95% CI
Semaglutide 1.0 mg	-4.3	± 13.4
Liraglutide 1.2 mg	-3.7	± 13.8

Adverse events — posted to ClinicalTrials.gov

Time frame: From the date of first dose of trial product (week 0) to end of treatment (week 30) + post treatment follow-up of 42 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide 1.0 mg

Serious: 17/289 (6%)

Deaths: 0/289

Liraglutide 1.2 mg

Serious: 22/287 (8%)

Deaths: 0/287

Serious adverse events (48 terms)

Reaction	System	Semaglutide 1.0 mg	Liraglutide 1.2 mg
Pyelonephritis	Infections and infestations	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Benign neoplasm of bladder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Bradycardia	Cardiac disorders	—	—
Calculus urinary	Renal and urinary disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Cardiovascular examination	Investigations	—	—
Cholecystitis	Hepatobiliary disorders	—	—
Cholecystitis acute	Hepatobiliary disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Cognitive disorder	Nervous system disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Confusional state	Psychiatric disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Depression	Psychiatric disorders	—	—
Device related infection	Infections and infestations	—	—
Diabetes mellitus inadequate control	Metabolism and nutrition disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Duodenal ulcer haemorrhage	Gastrointestinal disorders	—	—
Facial pain	General disorders	—	—
Haematuria	Renal and urinary disorders	—	—
Hepatic steatosis	Hepatobiliary disorders	—	—
Inguinal hernia	Gastrointestinal disorders	—	—

Other adverse events (9 terms — click to expand)

Reaction	System	Semaglutide 1.0 mg	Liraglutide 1.2 mg
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Nasopharyngitis	Infections and infestations	—	—
Vomiting	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Influenza	Infections and infestations	—	—

Most-reported serious reactions: Pyelonephritis, Abdominal pain upper, Acute kidney injury, Benign neoplasm of bladder, Bradycardia, Calculus urinary, Cardiac failure congestive, Cardiovascular examination.

Data from ClinicalTrials.gov NCT03191396 adverse events section.

Sponsor's own description

This study is conducted in Europe. The aim of the study is to compare the effect of semaglutide subcutaneous (s.c., under the skin) 1.0 mg once-weekly to liraglutide s.c.1.2 mg once-daily on blood sugar levels after 30 weeks of treatment in people with type 2 diabetes. The study will last approximately 9 months (37 weeks). Each participant will have 7 visits at the clinic and 3 phone calls with the study doctor. At the visits, participants will have a number of tests, for example: general health checks, blood samples, heart and eye checks etc. Participants will also fill in some forms about their health and satisfaction with their diabetes treatment.

Publications & conference data

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

1. 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
2. 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
3. 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
4. Superior weight loss with once-weekly semaglutide versus other glucagon-like peptide-1 receptor agonists is independent of gastrointestinal adverse events.
   Lingvay I, Hansen T, Macura S, Marre M, et al · · 2020 · cited 34× · PMID 33115821 · DOI 10.1136/bmjdrc-2020-001706
5. Hemoglobin A1c Reduction With the GLP-1 Receptor Agonist Semaglutide Is Independent of Baseline eGFR: <i>post hoc</i> Analysis of the SUSTAIN and PIONEER Programs.
   Cherney DZI, Hadjadj S, Lawson J, Mosenzon O, et al · · 2022 · cited 13× · PMID 36531884 · DOI 10.1016/j.ekir.2022.07.167
6. A model-based simulation of glycaemic control and body weight when switching from semaglutide to 3.0- and 4.5-mg doses of once-weekly dulaglutide.
   Tham LS, Pantalone KM, Dungan K, Munir K, et al · · 2022 · cited 11× · PMID 34697882 · DOI 10.1111/dom.14582
7. 57^th EASD Annual Meeting of the European Association for the Study of Diabetes.
   · 2021 · cited 11× · PMID 34468792 · DOI 10.1007/s00125-021-05519-y
8. 56^th EASD Annual Meeting of the European Association for the Study of Diabetes : 21-25 September 2020.
   · 2020 · cited 9× · PMID 32840677 · DOI 10.1007/s00125-020-05221-5