NCT03989232: SUSTAIN FORTE

A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes

Completed Phase 3 Results posted Last updated 13 February 2023

What this trial tests

Phase 3 trial testing Semaglutide in Diabetes Mellitus, Type 2 in 961 participants. Completed in 9 November 2020.

Timeline

19 June 2019

Primary endpoint
18 September 2020

9 November 2020

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	treatment
Enrollment	961
Start date	19 June 2019
Primary completion	18 September 2020
Estimated completion	9 November 2020
Sites	129 locations across Japan, Slovakia, Greece, Ukraine, Hungary, Poland, Canada, Puerto Rico

Drugs / interventions tested

• Semaglutide (semaglutide) — full drug profile →
• Placebo (semaglutide)

Conditions studied

• 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 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 40

Change from baseline (week 0) to week 40 in glycosylated haemoglobin (HbA1c) was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first; and 'In-trial' observation period which started at the date of randomisation and ended at the first of the following dates, both inclusive: end-of-treatment visit (week 40), death, participant withdrew informed consent, last contact for participant los

On-treatment without rescue medication

Group	Value	95% CI
Semaglutide 1.0 mg	-2.0	± 1.0
Semaglutide 2.0 mg	-2.2	± 1.0

In-trial

Group	Value	95% CI
Semaglutide 1.0 mg	-1.9	± 1.0
Semaglutide 2.0 mg	-2.2	± 1.1

Change in Body Weight Secondary · Week 0, week 40

Change from baseline (week 0) to week 40 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 of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first; and 'In-trial' observation period which started at the date of randomisation and ended at the first of the following dates, both inclusive: end-of-treatment visit (week 40), death, participant withdrew informed consent, last contact for participant lost to follow-up.

On-treatment without rescue medication

Group	Value	95% CI
Semaglutide 1.0 mg	-6.0	± 5.8
Semaglutide 2.0 mg	-7.0	± 5.8

In-trial

Group	Value	95% CI
Semaglutide 1.0 mg	-5.7	± 5.9
Semaglutide 2.0 mg	-6.7	± 5.9

Change in Fasting Plasma Glucose (FPG) Secondary · Week 0, week 40

Change from baseline (week 0) to week 40 in FPG was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first.

Group	Value	95% CI
Semaglutide 1.0 mg	-3.2	± 2.8
Semaglutide 2.0 mg	-3.4	± 3.1

Change in Body Mass Index (BMI) Secondary · Week 0, week 40

Change from baseline (week 0) to week 40 in BMI was evaluated. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first.

Group	Value	95% CI
Semaglutide 1.0 mg	-2.1	± 2.1
Semaglutide 2.0 mg	-2.5	± 2.1

Change in Waist Circumference Secondary · Week 0, week 40

Change from baseline (week 0) to week 40 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 of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first.

Group	Value	95% CI
Semaglutide 1.0 mg	-5.2	± 6.1
Semaglutide 2.0 mg	-5.9	± 6.2

Participants Who Achieved HbA1c < 7.0% Secondary · Week 40

Percentage of participants who achieved HbA1c \< 7.0% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing HbA1c assessment at week 40 was imputed using observed data from participants within same treatment group.

Group	Value	95% CI
Semaglutide 1.0 mg	57.5
Semaglutide 2.0 mg	67.6

Participants Who Achieved HbA1c ≤ 6.5% Secondary · Week 40

Percentage of participants who achieved HbA1c ≤ 6.5% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing HbA1c assessment at week 40 was imputed using observed data from participants within same treatment group.

Group	Value	95% CI
Semaglutide 1.0 mg	38.5
Semaglutide 2.0 mg	51.7

Participants Who Achieved Weight Loss ≥5% Secondary · Week 40

Percentage of participants who achieved weight loss ≥5% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing body weight assessment at week 40 was imputed using observed data from participants within same treatment group.

Group	Value	95% CI
Semaglutide 1.0 mg	51.3
Semaglutide 2.0 mg	59.2

Participants Who Achieved Weight Loss ≥10% Secondary · Week 40

Percentage of participants who achieved weight loss ≥10% is presented. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product to either first initiation of rescue medication or the day of last dose of trial product, whichever came first. Missing body weight assessment at week 40 was imputed using observed data from participants within same treatment group.

Group	Value	95% CI
Semaglutide 1.0 mg	22.6
Semaglutide 2.0 mg	28.4

Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes Secondary · Week 0 to week 47

Hypoglycaemic episodes defined as treatment-emergent if the onset of the episode occurs within the on-treatment observation period. Severe or BG-confirmed symptomatic hypoglycaemia is an episode that required assistance from another person for recovery and blood glucose-confirmed by a plasma glucose value \<3.1 mmol/L (56 milligrams per deciliter (mg/dL)) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: the follow-up visit (week 4

Group	Value	95% CI
Semaglutide 1.0 mg	28
Semaglutide 2.0 mg	21

Change in Pulse Rate Secondary · Week 0, week 40

Change from baseline (week 0) to week 40 in pulse rate is presented. Results are based on the 'on-treatment' observation period, which started at the date of first dose of trial product and ended at the endpoint-specific end-date.

Group	Value	95% CI
Semaglutide 1.0 mg	2.8	± 10.0
Semaglutide 2.0 mg	3.3	± 9.5

Adverse events — posted to ClinicalTrials.gov

Time frame: Weeks 0-47. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Semaglutide 1.0 mg

Serious: 25/480 (5%)

Deaths: 1/480

Semaglutide 2.0 mg

Serious: 21/479 (4%)

Deaths: 2/479

Serious adverse events (56 terms)

Reaction	System	Semaglutide 1.0 mg	Semaglutide 2.0 mg
Coronary artery stenosis	Cardiac disorders	—	—
Acute kidney injury	Renal and urinary disorders	—	—
Acute myocardial infarction	Cardiac disorders	—	—
Dehydration	Metabolism and nutrition disorders	—	—
Hypokalaemia	Metabolism and nutrition disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Adenocarcinoma pancreas	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Adenomyosis	Reproductive system and breast disorders	—	—
Anaemia	Blood and lymphatic system disorders	—	—
Angina pectoris	Cardiac disorders	—	—
Aortic dilatation	Vascular disorders	—	—
Aortic dissection	Vascular disorders	—	—
Aortic valve incompetence	Cardiac disorders	—	—
Asthma	Respiratory, thoracic and mediastinal disorders	—	—
Asymptomatic bacteriuria	Infections and infestations	—	—
Atrial fibrillation	Cardiac disorders	—	—
B-cell lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
COVID-19 pneumonia	Infections and infestations	—	—
Chest discomfort	General disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Chronic kidney disease	Renal and urinary disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Coronary artery disease	Cardiac disorders	—	—
Death; reason unknown	General disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Semaglutide 1.0 mg	Semaglutide 2.0 mg
Nausea	Gastrointestinal disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—

Most-reported serious reactions: Coronary artery stenosis, Acute kidney injury, Acute myocardial infarction, Dehydration, Hypokalaemia, Abdominal pain, Adenocarcinoma pancreas, Adenomyosis.

Data from ClinicalTrials.gov NCT03989232 adverse events section.

Sponsor's own description

This study compares the effect of two doses of semaglutide (1.0 mg and 2.0 mg) in people with type 2 diabetes (T2D). People taking part in the study will take the medicine together with their current diabetes medicine (sulphonylurea and/or metformin). Participants will get a dose of either 1.0 mg or 2.0 mg semaglutide once a week - which dose is decided by chance. Participants will inject semaglutide under the skin once a week. The study will last for about 49 weeks. Participants will have 9 clinic visits and 2 phone calls with the study doctor. At the visits participants will have blood taken and eye tests done. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period. Female participants who can get pregnant will be checked 11 times for pregnancy via urine tests.

Publications & conference data

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

1. Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial.
   Frías JP, Auerbach P, Bajaj HS, Fukushima Y, et al · · 2021 · cited 126× · PMID 34293304 · DOI 10.1016/s2213-8587(21)00174-1
2. 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
3. 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
4. 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
5. An Indirect Treatment Comparison of Semaglutide 2.0 mg vs Dulaglutide 3.0 mg and 4.5 mg Using Multilevel Network Meta-regression.
   Lingvay I, Bauer R, Baker-Knight J, Lawson J, et al · · 2022 · cited 14× · PMID 34922383 · DOI 10.1210/clinem/dgab905
6. 58^th EASD Annual Meeting of the European Association for the Study of Diabetes : Stockholm, Sweden, 19 - 23 September 2022.
   · 2022 · cited 6× · PMID 35920845 · DOI 10.1007/s00125-022-05755-w