parallel randomized trial

SUSTAIN 11

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

Type 2 diabetes (adults)NCT03689374S000363

Design

Randomized: 1,748
Start year: 2018
Treatment: 52 weeks, follow-up 57 weeks
Countries: multinational
Sponsor: Novo Nordisk (industry)
Eligibility: adults; HbA1c above 7.5 to 10.0 percent on insulin glargine plus metformin

Conduct and analysis

Blinding: open label
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	insulin glargine titrated plus metformin; lifestyle: not reported	874	874	826
A2	Insulin aspart (prandial) Insulin aspart TID	insulin glargine titrated plus metformin; lifestyle: not reported	874	874	806

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Semaglutide 1.0 mg subcutaneous once weekly A1	Insulin aspart (prandial) A2
age	mean (years)	60.8	61.5
age	sd (years)	9.4	9.5
asian	n	176	166
asian	percent	20.1	19.0
black	n	21	14
black	percent	2.4	1.6
bmi	mean (kg/m2)	31.4	31.7
bmi	sd (kg/m2)	5.5	5.5
diabetes duration	mean (years)	13.4	13.4
diabetes duration	sd (years)	6.8	6.5
egfr: 15 to 30	n	3	1
egfr: 15 to 30	percent	0.3	0.1
egfr: 30 to 60	n	55	52
egfr: 30 to 60	percent	6.3	5.9
egfr: 60 to 90	n	282	272
egfr: 60 to 90	percent	32.3	31.1
egfr: 90 or more	n	533	549
egfr: 90 or more	percent	61.0	62.8
egfr: less than 15	n	1	0
egfr: less than 15	percent	0.1
established cvd: coronary artery disease	n	51	52
established cvd: coronary artery disease	percent	5.8	5.9
established cvd: macroangiopathy	n	114	100
established cvd: macroangiopathy	percent	13.0	11.4
established cvd: previous myocardial ischemia	n	45	61
established cvd: previous myocardial ischemia	percent	5.1	7.0
female	n	429	425
hba1c	mean (percent)	8.6	8.5
hba1c	sd (percent)	0.7	0.7
hispanic	n	23	22
hispanic	percent	2.6	2.5
insulin dose	mean (U/day)	40.2	40.9
other coronary artery disease	n	51	52
other coronary artery disease	percent	5.8	5.9
other male	n	445	449
other male	percent	50.9	51.4
other metformin dose	mean (mg)	2059	2061
other metformin dose	sd (mg)	473.2	462.9
other race other	n	3	3
other race other	percent	0.3	0.3
weight	mean (kg)	87.6	88.1
weight	sd (kg)	18.1	18.4
white	n	674	691
white	percent	77.1	79.1

Analyses this trial contributes to

Results

73 adjudicated result lines, grouped by outcome. Open an outcome to see its values.

HbA1c change (5 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-1.5 percent	1.0		795	not stated; full analysis; registry:outcomes
52	A1	change	-1.5 percent			874	hypothetical; full analysis; R0022346:Results
52	A1 vs A2	md	-0.29 percent		-0.38 to -0.20		hypothetical; full analysis; R0022346:Results
52	A2	change	-1.2 percent			874	hypothetical; full analysis; R0022346:Results
52	A2	change	-1.2 percent	1.0		783	not stated; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (5 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-4.1 kg			874	hypothetical; full analysis; R0022346:Results
52	A1 vs A2	md	-6.99 kg		-7.41 to -6.57		hypothetical; full analysis; R0022346:Results
52	A1	change	-4.2 kg	4.6		801	not stated; full analysis; registry:outcomes
52	A2	change	2.9 kg	4.1		793	not stated; full analysis; registry:outcomes
52	A2	change	2.8 kg			874	hypothetical; full analysis; R0022346:Results

HbA1c below 7 percent (1 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	or	1.72		1.40 to 2.10		hypothetical; full analysis; R0022346:Results

Level 2 or 3 hypoglycemia (participants) (11 lines; O04)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			4 / 874	while on treatment; safety; R0022346:Table 4
A1	events			330 / 874	while on treatment; full analysis; R0022346:Table 2
A1	events			169 / 874	while on treatment; full analysis; R0022346:Table 2
A1	events			139 / 874	while on treatment; full analysis; R0022346:Table 2
A1	events			4 / 874	while on treatment; full analysis; R0022346:Table 2
A1 vs A2	hr	0.65	0.18 to 2.30		while on treatment; full analysis; R0022346:Results
A2	events			6 / 874	while on treatment; full analysis; R0022346:Table 2
A2	events			379 / 874	while on treatment; full analysis; R0022346:Table 2
A2	events			328 / 874	while on treatment; full analysis; R0022346:Table 2
A2	events			7 / 864	while on treatment; safety; R0022346:Table 4
A2	events			528 / 874	while on treatment; full analysis; R0022346:Table 2

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Estimate	95% CI	Detail
A1 vs A2	rate ratio	0.15	0.12 to 0.19	while on treatment; full analysis; R0022346:Table 2
A1	rate			while on treatment; full analysis; R0022346:Table 2
A1	rate			while on treatment; full analysis; R0022346:Table 2
A1 vs A2	rate ratio	0.58	0.15 to 2.20	while on treatment; full analysis; R0022346:Table 2
A2	rate			while on treatment; full analysis; R0022346:Table 2
A2	rate			while on treatment; full analysis; R0022346:Table 2

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	-3.9 mmHg		-5.0 to -2.7		hypothetical; full analysis; R0022346:Results
52	A1	change	-3.0 mmHg			874	hypothetical; full analysis; R0022346:Results
52	A1	change	-2.8 mmHg	13.8		784	not stated; full analysis; registry:outcomes
52	A2	change	1.0 mmHg	14.0		765	not stated; full analysis; registry:outcomes
52	A2	change	0.9 mmHg			874	hypothetical; full analysis; R0022346:Results

Percent body weight change (1 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	-8.03 percent		-8.52 to -7.55		hypothetical; full analysis; R0022346:Results

Weight loss of 5 percent or more (1 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	or	24.15		15.90 to 36.68		hypothetical; full analysis; R0022346:Results

Weight loss of 10 percent or more (1 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	or	35.98		13.25 to 97.71		hypothetical; full analysis; R0022346:Results

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				12 / 874	treatment policy; safety; R0022346:Table 3
	A2	events				1 / 864	treatment policy; safety; R0022346:Table 3

SF-36 physical component summary change (5 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	0.95 points		0.37 to 1.53		hypothetical; full analysis; R0022346:Results
52	A1	change	1.3 points			874	hypothetical; full analysis; R0022346:Results
52	A1	change	1.4 points	6.4		803	not stated; full analysis; registry:outcomes
52	A2	change	0.4 points	6.7		794	not stated; full analysis; registry:outcomes
52	A2	change	0.4 points			874	hypothetical; full analysis; R0022346:Results

Physical functioning (any instrument) (4 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
52	A1	change	1.4 points	7.7	803	not stated; full analysis; registry:outcomes
52	A1	change	2.4 points	24.6	802	not stated; full analysis; registry:outcomes
52	A2	change	0.2 points	7.8	794	not stated; full analysis; registry:outcomes
52	A2	change	-0.4 points	26.4	795	not stated; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				65 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				84 / 864	while on treatment; safety; R0022346:Table 3

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				32 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				6 / 864	while on treatment; safety; R0022346:Table 3

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				129 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				7 / 864	while on treatment; safety; R0022346:Table 3

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				50 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				5 / 864	while on treatment; safety; R0022346:Table 3

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				65 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				23 / 864	while on treatment; safety; R0022346:Table 3

Discontinuation due to gastrointestinal adverse events (2 lines; O27E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				15 / 874	while on treatment; safety; R0022346:Table 3
	A2	events				0 / 864	while on treatment; safety; R0022346:Table 3

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 874	not stated; safety; registry:adverse_events
	A2	events				2 / 864	not stated; safety; registry:adverse_events

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 874	not stated; safety; diabetic retinopathy; registry:adverse_events
	A2	events				1 / 864	not stated; safety; diabetic retinopathy; registry:adverse_events

Nonarteritic anterior ischemic optic neuropathy (2 lines; O34)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 874	not stated; safety; optic ischaemic neuropathy; registry:adverse_events
	A2	events				0 / 864	not stated; safety; optic ischaemic neuropathy; registry:adverse_events

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 874	not stated; safety; intestinal obstruction; registry:adverse_events
	A2	events				0 / 864	not stated; safety; intestinal obstruction; registry:adverse_events

Pancreatic cancer (6 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 874	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A1	events	0 / 874	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A1	events	0 / 874	not stated; safety; pancreatic carcinoma; registry:adverse_events
A2	events	0 / 864	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A2	events	1 / 864	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	1 / 864	not stated; safety; pancreatic carcinoma; registry:adverse_events