parallel randomized trial

SUSTAIN™ 3

Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes (SUSTAIN™ 3 - vs. QW GLP-1)

Type 2 diabetes (adults)NCT01885208S000329

Design

Randomized: 813
Start year: 2013
Treatment: 56 weeks, follow-up 61 weeks
Countries: Argentina, Croatia, Finland, France, Germany, Greece, Italy, Netherlands, Serbia, Switzerland, United Kingdom, United States
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older; T2D on stable 1 to 2 oral drugs; HbA1c 7.0 to 10.5 percent; eGFR 60 or more

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	1 to 2 oral drugs (metformin, thiazolidinedione, sulfonylurea); lifestyle: not reported	406	404	322
A2	Exenatide extended release 2 mg subcutaneous once weekly Exenatide ER 2.0 mg	1 to 2 oral drugs (metformin, thiazolidinedione, sulfonylurea); lifestyle: not reported	407	405	320

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	Exenatide extended release 2 mg subcutaneous once weekly A2	Whole trial ALL
age	mean (years)	56.4	56.7
age	sd (years)	10.3	11.1
asian	n	8	6
asian	percent	2.0	1.5
bmi	mean (kg/m2)			33.8
bmi	sd (kg/m2)			6.7
diabetes duration	mean (years)			9.2
diabetes duration	sd (years)			6.3
egfr	max (mL/min/1.73 m2)	208.0	194.0
egfr	mean (mL/min/1.73 m2)	100.5	100.5
egfr	min (mL/min/1.73 m2)	60.0	60.0
female	n	185	177
hba1c	mean (percent)	8.36	8.33
hba1c	sd (percent)	0.95	0.96
other background: metformin and sulfonylurea	percent			44.9
other background: metformin only	percent			49.6
other tzd use	percent			2.3
sbp	mean (mmHg)	133.35	133.66
sbp	sd (mmHg)	14.87	14.25
weight	mean (kg)	96.21	95.37
weight	sd (kg)	22.5	20.46

Analyses this trial contributes to

Results

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

HbA1c change (10 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1 vs A2	md	-0.62 percent		-0.80 to -0.44		hypothetical; full analysis; R0020680:Supplement Figure S3A
56	A1 vs A2	md	-0.38 percent		-0.63 to -0.12		hypothetical; full analysis; background:metformin_only; R0012216:Figure 1
56	A1	change	-1.75 percent	0.10			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1A
56	A1 vs A2	md	-0.90 percent		-1.16 to -0.64		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
56	A1	change	-1.54 percent	0.06		404	hypothetical; full analysis; registry:outcomes
56	A1 vs A2	md	-0.51 percent		-0.68 to -0.34		treatment policy; other; R0020680:Supplement Figure S3A
56	A1	change	-1.35 percent	0.09			hypothetical; full analysis; background:metformin_only; R0012216:Figure 1A
56	A2	change	-0.92 percent	0.06		405	hypothetical; full analysis; registry:outcomes
56	A2	change	-0.97 percent	0.10			hypothetical; full analysis; background:metformin_only; R0012216:Figure 1A
56	A2	change	-0.85 percent	0.09			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1A

Body weight change in kilograms (diabetes) (10 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1 vs A2	md	-5.07 kg		-6.26 to -3.88		hypothetical; full analysis; background:metformin_su; R0012216:Figure 1
56	A1	change	-5.63 kg	0.29		404	hypothetical; full analysis; registry:outcomes
56	A1 vs A2	md	-3.78 kg		-4.58 to -2.98		hypothetical; full analysis; R0020680:Supplement Figure S3B
56	A1 vs A2	md	-3.04 kg		-3.78 to -2.29		treatment policy; other; R0020680:Supplement Figure S3B
56	A1	change	-5.42 kg	0.41			hypothetical; full analysis; background:metformin_only; R0012216:Figure 1B
56	A1 vs A2	md	-2.96 kg		-4.14 to -1.79		hypothetical; full analysis; background:metformin_only; R0012216:Figure 1
56	A1	change	-6.08 kg	0.44			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1B
56	A2	change	-2.46 kg	0.44			hypothetical; full analysis; background:metformin_only; R0012216:Figure 1B
56	A2	change	-1.85 kg	0.29		405	hypothetical; full analysis; registry:outcomes
56	A2	change	-1.01 kg	0.42			hypothetical; full analysis; background:metformin_su; R0012216:Figure 1B

HbA1c below 7 percent (2 lines; O03)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1	responders	67			404	hypothetical; full analysis; R0013158:Table 1
56	A2	responders	40			405	hypothetical; full analysis; R0013158:Table 1

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events	8.2			404	not stated; safety; R0013158:Figure 5
	A2	events	8.1			405	not stated; safety; R0013158:Figure 5

Systolic blood pressure change (2 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1	change	-4.6 mmHg	0.68		404	hypothetical; full analysis; registry:outcomes
56	A2	change	-2.23 mmHg	0.7		405	hypothetical; 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
56	A1	responders	52			404	hypothetical; full analysis; R0009827:Figure 2
56	A2	responders	17			405	hypothetical; full analysis; R0009827:Figure 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1	responders	21			404	hypothetical; full analysis; R0013158:Table 1
56	A2	responders	4			405	hypothetical; full analysis; R0013158:Table 1

SF-36 physical component summary change (1 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1 vs A2	md	0.46 points		-0.64 to 1.56		hypothetical; full analysis; R0020680:Supplement Figure S5B

Physical functioning (any instrument) (1 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1 vs A2	md	0.43 points		-0.83 to 1.69		hypothetical; full analysis; R0020680:Supplement Figure S5B

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
56	A1	change	4.98 points	0.26		404	hypothetical; full analysis; registry:outcomes
56	A1 vs A2	md	1.02 points		0.28 to 1.76		hypothetical; full analysis; R0020680:Supplement Figure S5A
56	A2	change	3.96 points	0.27		405	hypothetical; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				38 / 404	while on treatment; safety; R0020680:Supplement Table S5
	A2	events				24 / 405	while on treatment; safety; R0020680:Supplement Table S5

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		39 / 404	not stated; safety; R0020680:Supplement Figure S2
A1	events	9	404	not stated; safety; R0013158:Supplement Table S4
A2	events		29 / 405	not stated; safety; R0020680:Supplement Figure S2

Nausea (4 lines; O27A)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		90 / 404	while on treatment; safety; registry:adverse_events
A1	events	22	404	not stated; safety; R0013158:Supplement Table S4
A2	events	12	405	not stated; safety; R0013158:Supplement Table S4
A2	events		48 / 405	while on treatment; safety; registry:adverse_events

Vomiting (4 lines; O27B)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	7	404	not stated; safety; R0013158:Supplement Table S4
A1	events		29 / 404	while on treatment; safety; registry:adverse_events
A2	events	6	405	not stated; safety; R0013158:Supplement Table S4
A2	events		25 / 405	while on treatment; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	11	404	not stated; safety; R0013158:Supplement Table S4
A1	events		46 / 404	while on treatment; safety; registry:adverse_events
A2	events	8	405	not stated; safety; R0013158:Supplement Table S4
A2	events		34 / 405	while on treatment; safety; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				26 / 404	while on treatment; safety; registry:adverse_events
	A2	events				21 / 405	while on treatment; 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	6			404	not stated; safety; R0013158:Supplement Table S4
	A2	events	3			405	not stated; safety; R0013158:Supplement Table S4

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 404	while on treatment; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 404	while on treatment; safety; cholecystitis acute; registry:adverse_events
A1	events	6 / 404	not stated; safety; cholelithiasis; R0013158:Supplement Table S4
A2	events	2 / 405	not stated; safety; cholelithiasis; R0013158:Supplement Table S4
A2	events	0 / 405	while on treatment; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 405	while on treatment; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 404	not stated; safety; pancreatitis; R0013158:Supplement Table S4
A1	events	3 / 404	while on treatment; safety; pancreatitis; registry:adverse_events
A2	events	3 / 405	not stated; safety; pancreatitis; R0013158:Supplement Table S4
A2	events	0 / 405	while on treatment; safety; pancreatitis; registry:adverse_events

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 404	while on treatment; safety; follicular thyroid cancer; registry:adverse_events
	A2	events				0 / 405	while on treatment; safety; follicular thyroid cancer; registry:adverse_events

Suicidal ideation or behavior (1 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				0 / 405	while on treatment; safety; R0020680:Supplement Table S5

Death by suicide (1 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				0 / 405	while on treatment; safety; R0020680:Supplement Table S5

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				8 / 404	not stated; safety; R0013158:Supplement Table S4
	A2	events				2 / 405	not stated; safety; R0013158:Supplement Table S4