parallel randomized trial

SUSTAIN™

Safety and Efficacy of Semaglutide Once Weekly Versus Sitagliptin Once Daily, Both as Monotherapy in Japanese Subjects With Type 2 Diabetes

Type 2 diabetes (adults)NCT02254291S002082

Design

Randomized: 308
Start year: 2014
Treatment: 30 weeks, follow-up 35 weeks
Countries: Japan
Sponsor: Novo Nordisk (industry)
Eligibility: Japanese; age 20 or older; HbA1c 6.5 to 9.5 percent on one OAD or 7.0 to 10.5 percent on diet and exercise

Conduct and analysis

Blinding: open label
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: while on treatment
Analysis population: safety
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg once weekly	diet and exercise therapy; monotherapy; lifestyle: not reported	103	103	100
A2	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg once weekly	diet and exercise therapy; monotherapy; lifestyle: not reported	102	102	87
A3	Sitagliptin Sitagliptin 100 mg once daily	diet and exercise therapy; monotherapy; lifestyle: not reported	103	103	100

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	Sitagliptin A3	Whole trial ALL
age	mean (years)	58.8	58.1	57.9
age	sd (years)	10.4	11.6	10.1
bmi	mean (kg/m2)	25.1	26.1	25.1
bmi	sd (kg/m2)	3.8	5.2	3.6
diabetes duration	mean (years)	8.0	7.8	8.1
diabetes duration	sd (years)	5.2	6.9	6.7
female	n	24	27	22
female	percent	23.3	26.5	21.4
hba1c	mean (percent)	8.2	8.0	8.2
hba1c	sd (percent)	1.0	0.9	0.9
sbp	mean (mmHg)				129.1
sbp	sd (mmHg)				14.8
waist	mean (cm)				89.7
waist	sd (cm)				10.8
weight	mean (kg)	67.8	70.8	69.4
weight	sd (kg)	11.7	16.4	12.9

Analyses this trial contributes to

Results

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

HbA1c change (27 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-1.13 percent		-1.32 to -0.94		hypothetical; full analysis; R0014736:Table 3
30	A1	change	-1.9 percent	0.1		103	hypothetical; full analysis; R0014736:Table 3
30	A1 vs A3	md	-1.04 percent		-1.24 to -0.83		treatment policy; full analysis; R0014736:Supplement Figure S4A
30	A1	change	-1.8 percent			37	hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
30	A1 vs A3	md	-0.99 percent		-1.33 to -0.65		hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
30	A1	change	-1.9 percent			66	hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
30	A1 vs A3	md	-1.18 percent		-1.41 to -0.95		hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
30	A1	change	-1.8 percent			46	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
30	A1 vs A3	md	-1.14 percent		-1.43 to -0.84		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
30	A1	change	-1.9 percent			57	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
30	A1 vs A3	md	-1.13 percent		-1.39 to -0.87		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
30	A2 vs A3	md	-1.06 percent		-1.41 to -0.71		hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
30	A2	change	-2.2 percent			56	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
30	A2 vs A3	md	-1.18 percent		-1.39 to -0.97		treatment policy; full analysis; R0014736:Supplement Figure S4A
30	A2	change	-2.2 percent			46	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
30	A2 vs A3	md	-1.48 percent		-1.78 to -1.19		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
30	A2	change	-1.8 percent			39	hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
30	A2 vs A3	md	-1.41 percent		-1.68 to -1.14		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
30	A2	change	-2.4 percent			63	hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
30	A2 vs A3	md	-1.62 percent		-1.86 to -1.38		hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
30	A2	change	-2.2 percent	0.1		102	hypothetical; full analysis; R0014736:Table 3
30	A2 vs A3	md	-1.44 percent		-1.63 to -1.24		hypothetical; full analysis; R0014736:Table 3
30	A3	change	-0.7 percent			44	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
30	A3	change	-0.7 percent	0.1		103	hypothetical; full analysis; R0014736:Table 3
30	A3	change	-0.7 percent			59	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
30	A3	change	-0.8 percent			30	hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
30	A3	change	-0.7 percent			73	hypothetical; full analysis; age:less_than_65; R0022277:Figure 1

Body weight change in kilograms (diabetes) (27 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-2.49 kg		-3.47 to -1.52		hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
30	A1	change	-2.2 kg	0.3		103	hypothetical; full analysis; R0014736:Table 3
30	A1 vs A3	md	-2.22 kg		-3.02 to -1.42		hypothetical; full analysis; R0014736:Table 3
30	A1 vs A3	md	-2.20 kg		-2.99 to -1.41		treatment policy; full analysis; R0014736:Supplement Figure S4B
30	A1	change	-2.1 kg			37	hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
30	A1 vs A3	md	-1.58 kg		-3.00 to -0.16		hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
30	A1	change	-2.3 kg			66	hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
30	A1	change	-2.1 kg			46	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
30	A1 vs A3	md	-2.25 kg		-3.46 to -1.03		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
30	A1	change	-2.3 kg			57	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
30	A1 vs A3	md	-2.21 kg		-3.28 to -1.15		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
30	A2 vs A3	md	-3.67 kg		-5.11 to -2.23		hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
30	A2	change	-3.9 kg	0.3		102	hypothetical; full analysis; R0014736:Table 3
30	A2	change	-3.7 kg			63	hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
30	A2 vs A3	md	-3.86 kg		-4.86 to -2.87		hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
30	A2	change	-4.2 kg			46	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
30	A2 vs A3	md	-4.36 kg		-5.58 to -3.14		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
30	A2	change	-3.5 kg			56	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
30	A2 vs A3	md	-3.47 kg		-4.57 to -2.37		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
30	A2 vs A3	md	-3.88 kg		-4.70 to -3.07		hypothetical; full analysis; R0014736:Table 3
30	A2 vs A3	md	-3.52 kg		-4.32 to -2.73		treatment policy; full analysis; R0014736:Supplement Figure S4B
30	A2	change	-4.2 kg			39	hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
30	A3	change	0.0 kg	0.3		103	hypothetical; full analysis; R0014736:Table 3
30	A3	change	0.1 kg			44	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
30	A3	change	-0.5 kg			30	hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
30	A3	change	-0.1 kg			59	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
30	A3	change	0.2 kg			73	hypothetical; full analysis; age:less_than_65; R0022277:Figure 2

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1 vs A3	or	16.53	7.39 to 36.99		hypothetical; full analysis; R0014736:Figure 2C
30	A1	responders	84		103	hypothetical; full analysis; R0014736:Table 3
30	A2	responders	95		102	hypothetical; full analysis; R0014736:Table 3
30	A2 vs A3	or	43.66	15.67 to 121.62		hypothetical; full analysis; R0014736:Figure 2C
30	A3	responders	35		103	hypothetical; full analysis; R0014736:Table 3

Level 2 or 3 hypoglycemia (participants) (6 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Results
A1	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5
A2	events	0 / 102	while on treatment; safety; R0014736:Results
A2	events	1 / 102	while on treatment; safety; R0014736:Supplement Table S5
A3	events	0 / 103	while on treatment; safety; R0014736:Results
A3	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5

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

Arm	Statistic	Events / N	Detail
A1	rate	103	while on treatment; safety; registry:outcomes
A2	rate	102	while on treatment; safety; registry:outcomes
A3	rate	103	while on treatment; safety; registry:outcomes

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-5.3 mmHg	1.1		103	hypothetical; full analysis; R0014736:Table 3
30	A1 vs A3	md	-2.54 mmHg		-5.64 to 0.55		hypothetical; full analysis; R0014736:Table 3
30	A2	change	-8.8 mmHg	1.2		102	hypothetical; full analysis; R0014736:Table 3
30	A2 vs A3	md	-6.01 mmHg		-9.16 to -2.85		hypothetical; full analysis; R0014736:Table 3
30	A3	change	-2.8 mmHg	1.1		103	hypothetical; full analysis; R0014736:Table 3

Weight loss of 5 percent or more (3 lines; O11A)

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	29	103	hypothetical; full analysis; R0014736:Table 3
30	A2	responders	57	102	hypothetical; full analysis; R0014736:Table 3
30	A3	responders	7	103	hypothetical; full analysis; R0014736:Table 3

Weight loss of 10 percent or more (3 lines; O11B)

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	7	103	hypothetical; full analysis; R0014736:Table 3
30	A2	responders	19	102	hypothetical; full analysis; R0014736:Table 3
30	A3	responders	0	103	hypothetical; full analysis; R0014736:Table 3

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Table 2
A2	events	0 / 102	while on treatment; safety; R0014736:Table 2
A3	events	0 / 103	while on treatment; safety; R0014736:Table 2

Three point MACE (3 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	2 / 103	while on treatment; safety; R0014736:Supplement Table S5
A2	events	0 / 102	while on treatment; safety; R0014736:Supplement Table S5
A3	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5
A2	events	0 / 102	while on treatment; safety; R0014736:Supplement Table S5
A3	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	6 / 103	while on treatment; safety; R0014736:Table 2
A2	events	2 / 102	while on treatment; safety; R0014736:Table 2
A3	events	2 / 103	while on treatment; safety; R0014736:Table 2

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	3 / 103	while on treatment; safety; R0014736:Table 2
A2	events	11 / 102	while on treatment; safety; R0014736:Table 2
A3	events	2 / 103	while on treatment; safety; R0014736:Table 2

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	11 / 103	while on treatment; safety; R0014736:Supplement Table S4
A2	events	13 / 102	while on treatment; safety; R0014736:Supplement Table S4
A3	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S4

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	7 / 103	while on treatment; safety; R0014736:Supplement Table S4
A2	events	9 / 102	while on treatment; safety; R0014736:Supplement Table S4
A3	events	2 / 103	while on treatment; safety; R0014736:Supplement Table S4

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	15 / 103	while on treatment; safety; R0014736:Supplement Table S4
A2	events	12 / 102	while on treatment; safety; R0014736:Supplement Table S4
A3	events	4 / 103	while on treatment; safety; R0014736:Supplement Table S4

Gallbladder and biliary disease (9 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; cholelithiasis; R0014736:Supplement Table S5
A1	events	0 / 103	while on treatment; safety; cholecystitis; registry:adverse_events
A1	events	1 / 103	while on treatment; safety; R0014736:Supplement Table S5
A2	events	1 / 102	while on treatment; safety; cholecystitis; registry:adverse_events
A2	events	1 / 102	while on treatment; safety; cholelithiasis; R0014736:Supplement Table S5
A2	events	3 / 102	while on treatment; safety; R0014736:Supplement Table S5
A3	events	0 / 103	while on treatment; safety; cholecystitis; registry:adverse_events
A3	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5
A3	events	0 / 103	while on treatment; safety; cholelithiasis; R0014736:Supplement Table S5

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Results
A2	events	0 / 102	while on treatment; safety; R0014736:Results
A3	events	0 / 103	while on treatment; safety; R0014736:Results

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Results
A2	events	0 / 102	while on treatment; safety; R0014736:Results
A3	events	0 / 103	while on treatment; safety; R0014736:Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Results
A2	events	0 / 102	while on treatment; safety; R0014736:Results
A3	events	0 / 103	while on treatment; safety; R0014736:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Table 2
A2	events	0 / 102	while on treatment; safety; R0014736:Table 2
A3	events	0 / 103	while on treatment; safety; R0014736:Table 2

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Results
A2	events	0 / 102	while on treatment; safety; R0014736:Results
A3	events	1 / 103	while on treatment; safety; R0014736:Results

Any cancer (3 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	0 / 103	while on treatment; safety; R0014736:Supplement Table S5
A2	events	1 / 102	while on treatment; safety; R0014736:Supplement Table S5
A3	events	1 / 103	while on treatment; safety; R0014736:Supplement Table S5