Phase 3 · Semaglutide

SUSTAIN 6 trial results

A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes (SUSTAIN™ 6 - Long-term Outcomes)

Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Stroke (percentage of subjects), Time from randomisation up to end of follow-up (scheduled at week 109). Semaglutide: 6.6; Placebo: 8.9.

Participants: 3,297
Status: completed
Completed: 2016-03-15
Sponsor: Novo Nordisk A/S

As posted on ClinicalTrials.gov (NCT01720446), updated at source Jun 27, 2019. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What SUSTAIN 6 measured first

Time From Randomisation to First Occurrence of a MACE, Defined as Cardiovascular Death, Non-fatal Myocardial Infarction, or Non-fatal Strokepercentage of subjects · Time from randomisation up to end of follow-up (scheduled at week 109) · number

Semaglutiden=1,648	Placebon=1,649
6.6	8.9

Side effects by arm

Side effects in SUSTAIN 6

Percent of participants affected, Adverse events from the first trial-related activity after the subject had signed the informed consent (week -2) until the end of the posttreatment follow-up period (week 109).. The most common events the registry lists.

Event	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo 0.5 mg	Placebo 1.0 mg
Any serious event	35%	33.6%	39.9%	36.1%
Nausea	17.3%	21.8%	7.5%	8%
Diarrhoea	17.9%	18%	11.8%	10.5%
Vomiting	10.5%	14.8%	5.1%	4%
Lipase increased	11.4%	10.9%	8%	8.4%
Decreased appetite	10.4%	9.1%	2.3%	1.1%
Constipation	5.6%	9.6%	4.5%	4.4%
Nasopharyngitis	8%	7.3%	9.5%	8%
Urinary tract infection	9.4%	8.6%	7.8%	8.2%
Headache	6.5%	7.1%	8.1%	9%
Upper respiratory tract infection	6.4%	6.2%	7.6%	7.9%
Dyspepsia	6.2%	7.7%	2.8%	2.2%
Arthralgia	5%	4.3%	6.9%	7%
Diabetic retinopathy	5.6%	6.8%	4.7%	4.6%
Cataract	6.7%	5.2%	4.5%	5.5%
Back pain	6.5%	6%	5.9%	5.8%
Dizziness	6.4%	5.6%	4.6%	4.6%
Bronchitis	5.6%	4.6%	5.9%	6.2%
Influenza	6.2%	5.8%	5.8%	5.6%
Amylase increased	3.8%	5.8%	3.4%	3.4%
Anaemia	5%	4%	5.3%	5.8%
Cough	4.4%	3.9%	4.9%	5.6%
Microalbuminuria	3.3%	4%	5.6%	5.1%
Pain in extremity	4.6%	3.5%	5.6%	5.1%
Abdominal pain	5.4%	4.3%	4%	3.8%
Abdominal pain upper	4.2%	5.1%	2.3%	2.3%

Secondary outcomes

What else it measured

Time From Randomisation to First Occurrence of an Expanded Composite Cardiovascular Outcomepercentage of subjects · Time from randomisation up to end of follow-up (scheduled at week 109) · number

Semaglutiden=1,648	Placebon=1,649
12.1	16.0

Time From Randomisation to Each Individual Component of the Expanded Composite Cardiovascular Outcomepercentage of subjects · Time from randomisation up to end of follow-up (scheduled at week 109) · number

Measure	Semaglutiden=1,648	Placebon=1,649
Cardiovascular death	1.6	1.9
Non-fatal MI	2.5	3.7
Non-fatal Stroke	1.5	2.5
Revascularisation	2.6	4.2
UAP requiring hospitalisation	1.1	1.3
Hospitalisation for heart failure	2.7	2.4

Time From Randomisation to First Occurrence of All-cause Death, Non-fatal MI, or Non-fatal Strokepercentage of subjects · Time from randomisation up to end of follow-up (scheduled at week 109) · number

Semaglutiden=1,648	Placebon=1,649
7.4	9.6

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Glycosylated Haemoglobin (HbA1c)percentage of glycosylated haemoglobin · Week 0, up to week 104 · least squares mean

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
-1.09(0.05)	-1.41(0.05)	-0.44(0.05)	-0.36(0.05)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Fasting Plasma Glucosemmol/L · Week 0, up to week 104 · least squares mean

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
-1.75(0.12)	-2.11(0.12)	-1.02(0.12)	-0.88(0.12)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Body Weightkg · Week 0, up to week 104 · least squares mean

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebon=1,649
-3.57(0.21)	-4.88(0.22)	-0.62(0.15)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Lipid Profilemg/dL · Week 0, up to week 104 · least squares mean

Measure	Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
Total cholesterol (mg/dL)	0.97(0.01)	0.97(0.01)	1.00(0.01)	0.99(0.01)
HDL-cholesterol (mg/dL)	0.99(0.01)	1.01(0.01)	0.99(0.01)	0.97(0.01)
LDL-cholesterol (mg/dL)	0.97(0.01)	0.98(0.01)	1.01(0.01)	0.99(0.01)
Triglycerides (mg/dL)	0.93(0.01)	0.92(0.01)	0.96(0.01)	0.98(0.01)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Urinary Albumin to Creatinine Ratiomg/g · Week 0, up to week 104 · least squares mean

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
1.02(0.05)	0.91(0.05)	1.32(0.07)	1.29(0.06)

Change From Baseline to Last Assessment in the Trial in Other Treatment Outcomes: Vital SignsmmHg · Week 0, up to week 104 · least squares mean

Measure	Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
Diastolic blood pressure (mmHg)	-1.37(0.32)	-1.57(0.32)	-1.42(0.32)	-1.71(0.32)
Systolic blood pressure (mmHg)	-3.44(0.54)	-5.37(0.54)	-2.17(0.54)	-2.78(0.54)

Incidence During the Trial in Other Treatment Outcomes: Hypoglycaemic EventsEvent rate per 100 exposure years · Week 0 - 109 · number

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
37.5	36.2	35.3	39.7

Incidence During the Trial in Other Treatment Outcomes: Adverse EventsEvent rate per 100 years of exposure · Weeks 0-109 · number

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822	Placebo 0.5 mgn=824	Placebo 1.0 mgn=825
330.5	337.0	317.4	298.3

Occurrence During the Trial in Other Treatment Outcomes: Anti-semaglutide AntibodiesPercentage of subjects · Weeks 0-109 · number

Semaglutide 0.5 mgn=826	Semaglutide 1.0 mgn=822
1.4	2.3

The trial

How SUSTAIN 6 was run

This trial is conducted globally. The aim of the trial is to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes. The trial is event-driven, i.e. the maximum trial duration (up to max. 148 weeks) will depend on the accrual of major adverse cardiovascular events (MACE) in this trial and the remaining research programme. The incidence of MACE will be monitored throughout the trial which will be terminated according to plan when pre-specified stopping criteria are met.

Semaglutide 0.5 mg
Semaglutide 1.0 mg
Semaglutide placebo 0.5 mg
Semaglutide placebo 1.0 mg

Who could join the trial

Inclusion Criteria: - Men and women with type 2 diabetes mellitus - Age above or equal to 50 years at screening and clinical evidence of cardiovascular disease or age above or equal to 60 years at screening and subclinical evidence of cardiovascular disease - Anti-diabetic drug naïve, or treated with one or two oral antidiabetic drug (OADs), or treated with human Neutral Protamin Hagedorn (NPH) insulin or long-acting insulin analogue or pre-mixed insulin, both types of insulin either alone or in combination with one or two OADs - HbA1c above or equal to 7.0% at screening Exclusion Criteria: - Type 1 diabetes mellitus - Use of glucagon-like peptide-1 (GLP-1) receptor agonist (exenatide, liraglutide, or other) or pramlintide within 90 days prior to screening - Use of any dipeptidyl peptidase 4 (DPP-IV) inhibitor within 30 days prior to screening - Treatment with insulin other than basal and pre-mixed insulin within 90 days prior to screening - except for short-term use in connection with intercurrent illness - Acute decompensation of glycaemic control requiring immediate intensification of treatment to prevent acute complications of diabetes (eg diabetes ketoacidosis) within 90 days prior to screening - History of chronic pancreatitis or idiopathic acute pancreatitis - Acute coronary or cerebro-vascular event within 90 days prior to randomisation - Currently planned coronary, carotid or peripheral artery revascularisation - Chronic heart failure New York Heart Association (NYHA) class IV - Personal or family history of multiple endocrine neoplasia type 2 (MEN2) or familial medullary thyroid carcinoma - Personal history of non-familial medullary thyroid carcinoma - Screening calcitonin above or equal to 50 ng/L

Published papers

Papers from SUSTAIN 6

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

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