parallel randomized trial

SUSTAIN™

Safety and Efficacy of Semaglutide Once Weekly in Monotherapy or in Combination With One OAD in Japanese Subjects With Type 2 Diabetes Who Are Insufficiently Controlled on Diet/Exercise Therapy or OAD Monotherapy

Type 2 diabetes (adults)NCT02207374S001498

Design

Randomized: 601
Start year: 2014
Treatment: 56 weeks, follow-up 61 weeks
Countries: Japan (41 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: Japanese adults 20 or older; HbA1c 7.0 to 10.5 percent; diet and exercise or OAD monotherapy; eGFR 30 or more

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg	diet and exercise or prestudy OAD monotherapy (SU, glinide, alpha glucosidase inhibitor or TZD); lifestyle: not reported	239	239	224
A2	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	diet and exercise or prestudy OAD monotherapy (SU, glinide, alpha glucosidase inhibitor or TZD); lifestyle: not reported	241	241	207
A3	Additional oad Additional OAD	diet and exercise or prestudy OAD monotherapy (SU, glinide, alpha glucosidase inhibitor or TZD); lifestyle: not reported	121	120	113

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	Additional oad A3	Whole trial ALL
age	mean (years)	58.0	58.7	59.2
age	sd (years)	10.6	10.2	10.1
bmi	mean (kg/m2)	26.2	26.4	26.7
bmi	sd (kg/m2)	4.8	4.7	4.6
diabetes duration	mean (years)	8.1	9.4	9.3
diabetes duration	sd (years)	6.0	6.5	7.0
egfr	mean (mL/min/1.73 m2)	101.4	101.6	102.0
egfr	sd (mL/min/1.73 m2)	21.7	24.0	22.5
female	n	73	67	31
female	percent	30.5	27.8	25.8
hba1c	mean (percent)	8.0	8.1	8.1
hba1c	sd (percent)	0.9	1.0	0.9
other background: alpha glucosidase inhibitor only	n	35	34	18
other background: alpha glucosidase inhibitor only	percent	14.6	14.1	15.0
other background: diet and exercise	n	68	68	35
other background: diet and exercise	percent	28.5	28.2	29.2
other background: glinide only	n	34	36	17
other background: glinide only	percent	14.2	14.9	14.2
other background: sulfonylurea only	n	68	69	33
other background: sulfonylurea only	percent	28.5	28.6	27.5
other background: thiazolidinedione only	n	34	34	17
other background: thiazolidinedione only	percent	14.2	14.1	14.2
sbp	mean (mmHg)				129.2
sbp	sd (mmHg)				13.0
waist	mean (cm)				91.9
waist	sd (cm)				11.9
weight	mean (kg)	71.0	71.7	72.2
weight	sd (kg)	15.4	15.9	14.9

Analyses this trial contributes to

Results

106 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
56	A1	change	-1.7 percent			220	hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	md	-1.08 percent		-1.24 to -0.91		hypothetical; modified itt; R0025024:Table 3
56	A1	change	-1.74 percent	0.05		220	hypothetical; full analysis; registry:outcomes
56	A1 vs A3	md	-1.03 percent		-1.31 to -0.75		hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
56	A1 vs A3	md	-1.10 percent		-1.31 to -0.90		hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
56	A1 vs A3	md	-1.06 percent		-1.27 to -0.84		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
56	A1 vs A3	md	-1.08 percent		-1.33 to -0.83		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
56	A2 vs A3	md	-1.29 percent		-1.55 to -1.03		hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 1
56	A2 vs A3	md	-1.31 percent		-1.60 to -1.02		hypothetical; full analysis; age:65_or_older; R0022277:Figure 1
56	A2 vs A3	md	-1.41 percent		-1.63 to -1.19		hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 1
56	A2 vs A3	md	-1.40 percent		-1.61 to -1.20		hypothetical; full analysis; age:less_than_65; R0022277:Figure 1
56	A2	change	-2.0 percent			204	hypothetical; modified itt; R0025024:Table 3
56	A2	change	-2.03 percent	0.05		204	hypothetical; full analysis; registry:outcomes
56	A2 vs A3	md	-1.37 percent		-1.53 to -1.20		hypothetical; modified itt; R0025024:Table 3
56	A3	change	-0.7 percent	0.1		106	hypothetical; modified itt; R0025024:Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
56	A1 vs A3	md	-2.46 kg		-3.90 to -1.03	hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
56	A1	change	-1.4 kg	0.2		hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	md	-1.84 kg		-2.67 to -1.01	hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	md	-1.55 kg		-2.58 to -0.51	hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
56	A1 vs A3	md	-1.45 kg		-2.56 to -0.35	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
56	A1 vs A3	md	-2.34 kg		-3.62 to -1.06	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
56	A2 vs A3	md	-4.05 kg		-5.52 to -2.58	hypothetical; full analysis; age:65_or_older; R0022277:Figure 2
56	A2 vs A3	md	-3.37 kg		-4.41 to -2.33	hypothetical; full analysis; age:less_than_65; R0022277:Figure 2
56	A2 vs A3	md	-2.90 kg		-4.01 to -1.80	hypothetical; full analysis; bmi:25_or_more; R0022277:Figure 2
56	A2 vs A3	md	-4.45 kg		-5.76 to -3.14	hypothetical; full analysis; bmi:less_than_25; R0022277:Figure 2
56	A2 vs A3	md	-3.59 kg		-4.43 to -2.75	hypothetical; modified itt; R0025024:Table 3
56	A2	change	-3.2 kg	0.2		hypothetical; modified itt; R0025024:Table 3
56	A3	change	0.4 kg	0.3		hypothetical; modified itt; R0025024:Table 3

HbA1c below 7 percent (5 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
56	A1	responders	84		239	hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	or	9.42	5.39 to 16.46		hypothetical; modified itt; R0025024:Table 3
56	A2	responders	91		241	hypothetical; modified itt; R0025024:Table 3
56	A2 vs A3	or	23.06	11.99 to 44.36		hypothetical; modified itt; R0025024:Table 3
56	A3	responders	42		120	hypothetical; modified itt; R0025024:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	3 / 239	while on treatment; safety; R0025024:Table 2
A1	events	0 / 239	while on treatment; safety; R0025024:Results
A2	events	0 / 241	while on treatment; safety; R0025024:Results
A2	events	6 / 241	while on treatment; safety; R0025024:Table 2
A3	events	2 / 120	while on treatment; safety; R0025024:Table 2
A3	events	0 / 120	while on treatment; safety; R0025024:Results

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

Arm	Statistic	Detail
A1	rate	while on treatment; safety; R0025024:Table 2
A2	rate	while on treatment; safety; R0025024:Table 2
A3	rate	while on treatment; safety; R0025024:Table 2

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Detail
56	A1	change	-2.0 mmHg	0.8		hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	md	-2.12 mmHg		-4.81 to 0.57	hypothetical; modified itt; R0025024:Table 3
56	A2	change	-3.7 mmHg	0.8		hypothetical; modified itt; R0025024:Table 3
56	A2 vs A3	md	-3.87 mmHg		-6.59 to -1.15	hypothetical; modified itt; R0025024:Table 3
56	A3	change	0.2 mmHg	1.1		hypothetical; modified itt; R0025024:Table 3

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
56	A1	responders	26		239	hypothetical; modified itt; R0025024:Table 3
56	A1 vs A3	or	5.61	2.51 to 12.51		hypothetical; modified itt; R0025024:Table 3
56	A2	responders	46		241	hypothetical; modified itt; R0025024:Table 3
56	A2 vs A3	or	14.83	6.69 to 32.85		hypothetical; modified itt; R0025024:Table 3
56	A3	responders	6		120	hypothetical; modified itt; R0025024:Table 3

Weight loss of 10 percent or more (5 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
56	A1 vs A3	or	7.41	1.42 to 38.73		hypothetical; modified itt; R0025024:Table 3
56	A1	responders	8		239	hypothetical; modified itt; R0025024:Table 3
56	A2	responders	17		241	hypothetical; modified itt; R0025024:Table 3
56	A2 vs A3	or	17.69	3.48 to 89.99		hypothetical; modified itt; R0025024:Table 3
56	A3	responders	1		120	hypothetical; modified itt; R0025024:Table 3

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 239	while on treatment; safety; R0025024:Table 2
A2	events	0 / 241	while on treatment; safety; R0025024:Table 2
A3	events	1 / 120	while on treatment; safety; R0025024:Table 2

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	1 / 239	while on treatment; safety; R0025024:Table 2
A2	events	0 / 241	while on treatment; safety; R0025024:Table 2
A3	events	0 / 120	while on treatment; safety; R0025024:Table 2

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	19 / 239	while on treatment; safety; R0025024:Table 2
A2	events	12 / 241	while on treatment; safety; R0025024:Table 2
A3	events	8 / 120	while on treatment; safety; R0025024:Table 2

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	14 / 239	while on treatment; safety; R0025024:Table 2
A2	events	26 / 241	while on treatment; safety; R0025024:Table 2
A3	events	4 / 120	while on treatment; safety; R0025024:Table 2

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	29 / 239	while on treatment; safety; R0025024:Table 2
A2	events	46 / 241	while on treatment; safety; R0025024:Table 2
A3	events	1 / 120	while on treatment; safety; R0025024:Table 2

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	13 / 239	while on treatment; safety; R0025024:Table 2
A2	events	14 / 241	while on treatment; safety; R0025024:Table 2
A3	events	2 / 120	while on treatment; safety; R0025024:Table 2

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	24 / 239	while on treatment; safety; R0025024:Table 2
A2	events	38 / 241	while on treatment; safety; R0025024:Table 2
A3	events	8 / 120	while on treatment; safety; R0025024:Table 2

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	45 / 239	while on treatment; safety; R0025024:Table 2
A2	events	36 / 241	while on treatment; safety; R0025024:Table 2
A3	events	5 / 120	while on treatment; safety; R0025024:Table 2

Discontinuation due to gastrointestinal adverse events (3 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	7 / 239	while on treatment; safety; R0025024:Figure 1
A2	events	18 / 241	while on treatment; safety; R0025024:Figure 1
A3	events	0 / 120	while on treatment; safety; R0025024:Figure 1

Gallbladder and biliary disease (3 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	4 / 239	while on treatment; safety; cholelithiasis; R0025024:Results
A2	events	2 / 241	while on treatment; safety; cholelithiasis; R0025024:Results
A3	events	0 / 120	while on treatment; safety; cholelithiasis; R0025024:Results

Acute pancreatitis (3 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 239	while on treatment; safety; R0025024:Results
A2	events	0 / 241	while on treatment; safety; R0025024:Results
A3	events	0 / 120	while on treatment; safety; R0025024:Results

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 239	while on treatment; safety; R0025024:Results
A2	events	0 / 241	while on treatment; safety; R0025024:Results
A3	events	0 / 120	while on treatment; safety; R0025024:Results

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	11 / 239	while on treatment; safety; diabetic retinopathy; R0025024:Table 2
A2	events	16 / 241	while on treatment; safety; diabetic retinopathy; R0025024:Table 2
A3	events	6 / 120	while on treatment; safety; diabetic retinopathy; R0025024:Table 2

Death by suicide (1 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A2	events				0 / 241	while on treatment; safety; R0025024:Table 2

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 239	while on treatment; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 241	while on treatment; safety; intestinal obstruction; registry:adverse_events
A3	events	0 / 120	while on treatment; safety; intestinal obstruction; registry:adverse_events

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 239	while on treatment; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	0 / 241	while on treatment; safety; pancreatic carcinoma metastatic; registry:adverse_events
A3	events	1 / 120	while on treatment; safety; pancreatic carcinoma metastatic; registry:adverse_events

Any cancer (3 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	4 / 239	while on treatment; safety; R0025024:Table 2
A2	events	3 / 241	while on treatment; safety; R0025024:Table 2
A3	events	3 / 120	while on treatment; safety; R0025024:Table 2