parallel randomized trial

SUSTAIN 9

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus. A 30-week Randomised, Double-blind, Placebo-controlled Trial

Type 2 diabetes (adults)NCT03086330S000483

Design

Randomized: 302
Start year: 2017
Treatment: 30 weeks, follow-up 36 weeks
Countries
Sponsor: Novo Nordisk A/S (industry)
Eligibility: adults 18 or older (20 in Japan); HbA1c 7.0 to 10.5 percent; stable SGLT2i with or without metformin or SU

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
Outcome adjudication: not reported
Primary estimand: not stated
Analysis population: full analysis
Missing data: ANCOVA with multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	SGLT2i with or without metformin or sulfonylurea; lifestyle: not reported	151	151
A2	Placebo Placebo	SGLT2i with or without metformin or sulfonylurea; lifestyle: not reported	151	151

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	Placebo A2	Whole trial ALL
age	mean (years)	57.5	56.6
age	sd (years)	8.9	10.1
asian	n	36	35
black	n	9	4
bmi	mean (kg/m2)			31.9
bmi	sd (kg/m2)			6.6
diabetes duration	mean (years)			9.7
diabetes duration	sd (years)			6.1
egfr	mean (mL/min/1.73 m2)			95.2
egfr	sd (mL/min/1.73 m2)			15.2
female	n	62	64
hba1c	mean (percent)	8.0	8.1
hba1c	sd (percent)	0.8	0.8
hispanic	n	9	13
other fpg	mean (mmol/L)			9.0
other race american indian alaska native	n	2	0
other race native hawaiian pacific islander	n	0	0
other race other	n	4	3
weight	mean (kg)			91.7
weight	sd (kg)			21.0
white	n	100	109

Analyses this trial contributes to

Results

50 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
30	A1	change	-1.6 percent	0.8		151	not stated; full analysis; registry:outcomes
30	A1 vs A2	md	-1.42 percent		-1.61 to -1.24		hypothetical; full analysis; R0021710:Figure 1
30	A1 vs A2	md	-1.42 percent		-1.61 to -1.24		not stated; full analysis; registry:outcomes
30	A1 vs A2	md	-2.00 percent		-2.36 to -1.65		hypothetical; full analysis; region:japan; R0021710:Figure 1
30	A2	change	-0.2 percent	0.9		151	not stated; full analysis; registry:outcomes

Body weight change in kilograms (diabetes) (4 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-3.81 kg		-4.70 to -2.93		hypothetical; full analysis; R0021710:Figure 3b
30	A1	change	-4.7 kg	4.3		151	not stated; full analysis; registry:outcomes
30	A1 vs A2	md	-3.81 kg		-4.70 to -2.93		not stated; full analysis; registry:outcomes
30	A2	change	-1.0 kg	3.1		151	not stated; full analysis; registry:outcomes

HbA1c below 7 percent (4 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	79	151	hypothetical; full analysis; R0021710:Figure 2
30	A1	responders	82.5	120	not stated; full analysis; registry:outcomes
30	A2	responders	20.5	127	not stated; full analysis; registry:outcomes
30	A2	responders	19	151	hypothetical; full analysis; R0021710:Figure 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 150	while on treatment; safety; R0021710:Table 2
	A2	events				0 / 151	while on treatment; safety; R0021710:Table 2

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-4.3 mmHg	14.5		151	not stated; full analysis; registry:outcomes
30	A2	change	1.1 mmHg	12.3		151	not stated; full analysis; registry:outcomes

Percent body weight change (3 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A2	md	-4.38 percent		-5.36 to -3.39		hypothetical; full analysis; R0021710:Figure 3a
30	A1	percent change	-5.4 percent	4.8		151	not stated; full analysis; registry:outcomes
30	A2	percent change	-1.0 percent	3.1		151	not stated; full analysis; registry:outcomes

Weight loss of 5 percent or more (2 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	responders	50.4			121	not stated; full analysis; registry:outcomes
30	A2	responders	7.8			128	not stated; full analysis; registry:outcomes

Weight loss of 10 percent or more (2 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	responders	15.7			121	not stated; full analysis; registry:outcomes
30	A2	responders	1.6			128	not stated; full analysis; registry:outcomes

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 150	not stated; safety; registry:adverse_events
	A2	events				0 / 151	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 150	not stated; safety; registry:adverse_events
	A2	events				0 / 151	not stated; safety; registry:adverse_events

SF-36 physical component summary change (2 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	1.9 points	4.9		151	hypothetical; full analysis; registry:outcomes
30	A2	change	0.7 points	5.4		151	hypothetical; full analysis; registry:outcomes

Physical functioning (any instrument) (2 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	1.3 points	4.1		151	hypothetical; full analysis; registry:outcomes
30	A2	change	1.1 points	5.2		151	hypothetical; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (2 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	4.2 points	6.6		151	not stated; full analysis; registry:outcomes
30	A2	change	1.9 points	7.0		151	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				7 / 150	while on treatment; safety; R0021710:Table 2
	A2	events				6 / 151	while on treatment; safety; R0021710:Table 2

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				13 / 150	while on treatment; safety; R0021710:Table 2
	A2	events				3 / 151	while on treatment; safety; R0021710:Table 2

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				29 / 150	not stated; safety; registry:adverse_events
	A2	events				5 / 151	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				14 / 150	not stated; safety; registry:adverse_events
	A2	events				3 / 151	not stated; safety; registry:adverse_events

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 150	not stated; safety; registry:adverse_events
	A2	events				9 / 151	not stated; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 150	not stated; safety; registry:adverse_events
	A2	events				0 / 151	not stated; safety; registry:adverse_events

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 150	while on treatment; safety; R0021710:Table 2
	A2	events				0 / 151	while on treatment; safety; R0021710:Table 2

Diabetic retinopathy complications (2 lines; O33)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 150	not stated; safety; diabetic retinopathy; registry:adverse_events
	A2	events				8 / 151	not stated; safety; diabetic retinopathy; registry:adverse_events