Phase 3 · Semaglutide

SUSTAIN 11 trial results

Effect of Semaglutide Once-weekly Versus Insulin Aspart Three Times Daily, Both as Add on to Metformin and Optimised Insulin Glargine (U100) in Subjects With Type 2 Diabetes A 52-week, Multi-centre, Multinational, Open-label, Active-controlled, Two Armed, Parallel-group, Randomised Trial in Subjects With Type 2 Diabetes

Change From Baseline in Glycated Haemoglobin (HbA1c) (Percentage of HbA1c), Baseline (week 0), week 52. Semaglutide: -1.5; Insulin Aspart: -1.2.

Participants: 2,274
Status: completed
Completed: 2021-02-22
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT03689374), updated at source Nov 14, 2022. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What SUSTAIN 11 measured first

Change From Baseline in Glycated Haemoglobin (HbA1c)Percentage of HbA1c · Baseline (week 0), week 52 · mean

Semaglutiden=795	Insulin Aspartn=783
-1.5(1.0)	-1.2(1.0)

Side effects by arm

Side effects in SUSTAIN 11

Percent of participants affected, From week 0 to week 52. The most common events the registry lists.

Event	Semaglutide	Insulin Aspart
Any serious event	7.4%	9.7%
Nausea	14.8%	0.8%
Diarrhoea	7.4%	2.7%
Nasopharyngitis	6.5%	5.9%
Vomiting	5.7%	0.6%

Secondary outcomes

What else it measured

Time to First Event Adjudication Committee (EAC)-Confirmed Severe Hypoglycaemic Episode American Diabetes Association (ADA) From Randomization up to Week 52First event per 100 years of exposure · From randomization (week 0) up to week 52 · number

Semaglutiden=874	Insulin Aspartn=864
0.4	0.7

Time to First Event Adjudication Committee-confirmed Severe Hypoglycaemic Episode (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening Randomization up to Week 52First event per 100 years of exposure · From randomization (week 0) up to week 52 · number

Semaglutiden=874	Insulin Aspartn=864
0.2	0.4

Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) From Randomization to Week 52Episodes · From randomization (week 0) to week 52 · number

Semaglutiden=874	Insulin Aspartn=874
4	7

Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose (BG) Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose Less Than (<) 3.1 mmol/L (56 mg/dL)) From Randomization to Week 52Episodes · From randomization (week 0) to week 52 · number

Semaglutiden=874	Insulin Aspartn=874
254	1744

Number of Event Adjudication Committee-confirmed Severe (ADA) or Blood Glucose Confirmed, Symptomatic Hypoglycaemic Episodes (Plasma Glucose <= 3.9 mmol/L (70 mg/dL)) From Randomization to Week 52Episodes · From randomization (week 0) to week 52 · number

Semaglutiden=874	Insulin Aspartn=874
1420	5616

Number of Event Adjudication Committee-confirmed Severe Hypoglycaemic Episodes (ADA) Requiring Hospitalization, Documented Medical Help, or is Life-threatening From Randomization to Week 52Episodes · From randomization (week 0) to week 52 · number

Semaglutiden=874	Insulin Aspartn=874
2	4

Number of Event Adjudication Committee-confirmed Severe (ADA) or Clinically Significant Hypoglycaemic Episodes (Plasma Glucose < 3.0 mmol/L (54 mg/dL)) From Randomization to Week 52Episodes · From randomization (week 0) to week 52 · number

Semaglutiden=874	Insulin Aspartn=874
339	2270

Daily Basal Insulin Dose at Week 52Units of insulin · At week 52 · mean

Semaglutiden=803	Insulin Aspartn=794
35.8(19.4)	40.7(22.0)

Total Daily Insulin Dose at Week 52Units of insulin · At week 52 · mean

Semaglutiden=803	Insulin Aspartn=797
35.8(19.4)	77.7(40.0)

Change From Baseline to Week 52 in Body Weight (Kilogram (kg))kilograms · Baseline (week 0), week 52 · mean

Semaglutiden=801	Insulin Aspartn=793
-4.2(4.6)	2.9(4.1)

Change From Baseline to Week 52 in Fasting Plasma Glucose (FPG)millimoles per liter (mmol/L) · Baseline (week 0), week 52 · mean

Semaglutiden=770	Insulin Aspartn=762
-1.3(2.9)	-0.8(3.1)

Change From Baseline to Week 52 in 7-point Self-measured Plasma Glucose Profile (SMPG ): Mean 7-point Profile (7-PP)mmol/L · Baseline (week 0), week 52 · mean

Semaglutiden=757	Insulin Aspartn=737
-2.1(2.0)	-2.1(2.0)

The trial

How SUSTAIN 11 was run

This study will compare the effect of semaglutide once weekly to insulin aspart 3 times daily as add on to metformin and insulin glargine in people with type 2 diabetes. Participants will either get insulin glargine and semaglutide or insulin glargine and insulin aspart - which treatment the participant get is decided by chance. Insulin glargine is taken once a day and semaglutide once a week. Insulin aspart is taken three times per day before a meal. All three medicines come in pre-filled pens for injection under the skin. The study will last for about 71 weeks. If participant's blood sugar gets under or over certain values participant will only participate in 14 weeks. The study doctor will inform the participant about this. The participant will have 15 clinic visits and 22 phone calls with the study doctor.

Semaglutide: Run-in period (12 weeks): subjects will be treated with metformin and insulin glargine (IGlar) U100. Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in will receive semaglutide for 52 weeks in addition to metformin and IGlar U100. Metformin will be considered as background therapy during the trial.
Insulin aspart: Run-in period (12 weeks): subjects will be treated with metformin and insulin IGlar U100. Treatment period: Participants who are not in glycaemic control (defined as HbA1c of more than or equal to 7.5% to less than or equal to 10%) after run-in receive insulin aspart for 52 weeks in addition to metformin and IGlar U100. Metformin will be considered as background therapy during the trial.

Who could join the trial

Inclusion Criteria: * Male or female, age greater than or equal to 18 years at the time of signing informed consent * Diagnosed with type 2 diabetes greater than or equal to 180 days prior to the day of screening * Treated with basal insulin once daily or twice daily for greater than or equal to 90 days prior to the day of screening * Stable daily dose for 90 days prior to the day of screening of the following anti-diabetic drugs or combination regimens: Any metformin formulations (greater than or equal to 1500 mg to less than or equal to 3000 mg or maximum tolerated or effective dose documented in subject's medical record), alone or in combination (including fixed-dose drug combination) with up to one additional of the following oral antidiabetic drugs: sulfonylureas, meglitinides, dipeptidyl peptidase-4 inhibitors or alpha-glucosidase inhibitors * Glycated haemoglobin (HbA1c) of greater than 7.5% to less than or less than or equal to 10.0% (greater than 58 mmol/mol to less than or equal to 86 mmol/mol) Exclusion Criteria: * History or presence of pancreatitis (acute or chronic) * Any of the following: myocardial infarction, 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 Class IV * Planned coronary, carotid or peripheral artery revascularisation known on the day of 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 bolus insulin treatment for a maximum of 14 days prior to the day of screening is allowed * Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (for example, optometrist) within the past 90 days prior to run-in

Published papers

Papers from SUSTAIN 11

Kellerer M, Kaltoft MS, Lawson J, Nielsen LL, Strojek K, Tabak O, Jacob S. Effect of once-weekly semaglutide versus thrice-daily insulin aspart, both as add-on to metformin and optimized insulin glargine treatment in participants with type 2 diabetes (SUSTAIN 11): A randomized, open-label, multinational, phase 3b trial. Diabetes Obes Metab. 2022 Sep;24(9):1788-1799. doi: 10.1111/dom.14765. Epub 2022 Jun 29.

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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