parallel randomized trial

SUSTAIN™ 4

Efficacy and Safety of Semaglutide Once Weekly Versus Insulin Glargine Once Daily as Add on to Metformin With or Without Sulphonylurea in Insulin-naïve Subjects With Type 2 Diabetes

Type 2 diabetes (adults)NCT02128932S001219

Design

Randomized: 1,089
Start year: 2014
Treatment: 30 weeks, follow-up 35 weeks
Countries
Sponsor: Novo Nordisk A/S (industry)
Eligibility: adults with T2D, insulin naive, on metformin with or without SU; HbA1c 7.0 to 10.0 percent

Conduct and analysis

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

Arms

Arm	Treatment	Background	Analyzed
A1	Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg	metformin with or without sulfonylurea; lifestyle: not reported	362
A2	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	metformin with or without sulfonylurea; lifestyle: not reported	360
A3	Insulin glargine Insulin glargine	metformin with or without sulfonylurea; lifestyle: not reported	360

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 0.5 mg subcutaneous once weekly A1	Semaglutide 1.0 mg subcutaneous once weekly A2	Insulin glargine A3	Whole trial ALL
age	mean (years)	56.5	56.7	56.2
age	sd (years)	10.3	10.4	10.6
bmi	mean (kg/m2)				33.0
bmi	sd (kg/m2)				6.5
diabetes duration	mean (years)				8.6
diabetes duration	sd (years)				6.3
egfr	mean (mL/min/1.73 m2)				96.1
egfr	sd (mL/min/1.73 m2)				17.8
female	n	165	178	165
female	percent				47.0
hba1c	mean (percent)	8.13	8.25	8.13
hba1c	sd (percent)	0.85	0.94	0.88
metformin use	n				1082
metformin use	percent				100
other background metformin and su	percent				51.6
other background metformin only	percent				48.3
other egfr below 60	n				43
other egfr below 60	percent				4.0
other retinopathy history	n				50
other retinopathy history	percent				4.6
sbp	mean (mmHg)	131.57	132.21	132.38
sbp	sd (mmHg)	14.06	16.05	15.77
uacr	mean (mg/g)				14.7
weight	mean (kg)	93.73	94.00	92.61
weight	sd (kg)	21.39	22.48	21.52

Analyses this trial contributes to

Results

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

HbA1c change (15 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-0.32 percent		-0.52 to -0.12		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A1 vs A3	md	-0.38 percent		-0.52 to -0.24		not stated; full analysis; registry:outcomes
30	A1	change	-1.21 percent	0.05		362	not stated; full analysis; registry:outcomes
30	A1	change	-1.18 percent	0.08			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A1 vs A3	md	-0.45 percent		-0.66 to -0.24		hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A1	change	-1.23 percent	0.07			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A2	change	-1.68 percent	0.07			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A2	change	-1.64 percent	0.05		360	not stated; full analysis; registry:outcomes
30	A2 vs A3	md	-0.81 percent		-0.96 to -0.67		not stated; full analysis; registry:outcomes
30	A2 vs A3	md	-0.77 percent		-0.97 to -0.57		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A2	change	-1.62 percent	0.08			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A2 vs A3	md	-0.89 percent		-1.09 to -0.68		hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A3	change	-0.73 percent	0.07			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A3	change	-0.91 percent	0.07			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A3	change	-0.83 percent	0.05		360	not stated; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (13 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-3.36 kg	0.33			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A1	change	-3.47 kg	0.24		362	not stated; full analysis; registry:outcomes
30	A1 vs A3	md	-4.72 kg		-5.63 to -3.81		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A1	change	-3.60 kg	0.35			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A1 vs A3	md	-4.58 kg		-5.53 to -3.64		hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A2	change	-5.78 kg	0.35			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A2 vs A3	md	-6.76 kg		-7.72 to -5.81		hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A2	change	-4.56 kg	0.34			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A2	change	-5.17 kg	0.24		360	not stated; full analysis; registry:outcomes
30	A2 vs A3	md	-5.90 kg		-6.82 to -4.99		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A3	change	0.98 kg	0.34			hypothetical; full analysis; background:metformin; R0012216:Figure 1
30	A3	change	1.35 kg	0.32			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
30	A3	change	1.15 kg	0.23		360	not stated; full analysis; registry:outcomes

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
30	A1	change	-4.65 mmHg	0.72	362	not stated; full analysis; registry:outcomes
30	A2	change	-5.17 mmHg	0.73	360	not stated; full analysis; registry:outcomes
30	A3	change	-1.68 mmHg	0.68	360	not stated; full analysis; registry:outcomes

Acute kidney injury (3 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 362	not stated; safety; registry:adverse_events
A2	events	1 / 360	not stated; safety; registry:adverse_events
A3	events	0 / 360	not stated; safety; registry:adverse_events

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	2 / 362	not stated; full analysis; registry:flow
A2	events	0 / 360	not stated; full analysis; registry:flow
A3	events	2 / 360	not stated; full analysis; registry:flow

SF-36 physical component summary change (3 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
30	A1	change	1.18 points	0.36	362	not stated; full analysis; registry:outcomes
30	A2	change	2.09 points	0.36	360	not stated; full analysis; registry:outcomes
30	A3	change	1.18 points	0.34	360	not stated; full analysis; registry:outcomes

Physical functioning (any instrument) (3 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
30	A1	change	1.64 points	0.43	362	not stated; full analysis; registry:outcomes
30	A2	change	1.49 points	0.43	360	not stated; full analysis; registry:outcomes
30	A3	change	0.69 points	0.41	360	not stated; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
30	A1	change	4.86 points	0.28	362	not stated; full analysis; registry:outcomes
30	A2	change	5.37 points	0.29	360	not stated; full analysis; registry:outcomes
30	A3	change	3.99 points	0.27	360	not stated; full analysis; registry:outcomes

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	22 / 362	not stated; safety; registry:adverse_events
A2	events	17 / 360	not stated; safety; registry:adverse_events
A3	events	18 / 360	not stated; safety; registry:adverse_events

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	77 / 362	not stated; safety; registry:adverse_events
A1	events	0 / 362	not stated; safety; registry:adverse_events
A2	events	80 / 360	not stated; safety; registry:adverse_events
A2	events	0 / 360	not stated; safety; registry:adverse_events
A3	events	12 / 360	not stated; safety; registry:adverse_events
A3	events	1 / 360	not stated; safety; registry:adverse_events

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	24 / 362	not stated; safety; registry:adverse_events
A1	events	0 / 362	not stated; safety; registry:adverse_events
A2	events	37 / 360	not stated; safety; registry:adverse_events
A2	events	0 / 360	not stated; safety; registry:adverse_events
A3	events	10 / 360	not stated; safety; registry:adverse_events
A3	events	1 / 360	not stated; safety; registry:adverse_events

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	59 / 362	not stated; safety; registry:adverse_events
A2	events	69 / 360	not stated; safety; registry:adverse_events
A3	events	16 / 360	not stated; safety; registry:adverse_events

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 362	not stated; safety; registry:adverse_events
A2	events	0 / 360	not stated; safety; registry:adverse_events
A3	events	0 / 360	not stated; safety; registry:adverse_events

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 362	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 360	not stated; safety; intestinal obstruction; registry:adverse_events
A3	events	0 / 360	not stated; safety; intestinal obstruction; registry:adverse_events

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 362	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	0 / 360	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A3	events	0 / 360	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events