parallel randomized trial

SUSTAIN™ 5

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to Basal Insulin Alone or Basal Insulin in Combination With Metformin in Subjects With Type 2 Diabetes

Type 2 diabetes (adults)NCT02305381S001872

Design

Randomized: 397
Start year: 2014
Treatment: 30 weeks, follow-up 35 weeks
Countries: Germany, Japan, Serbia, Slovakia, United States (90 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older (20 in Japan); HbA1c 7.0 to 10.0 percent; stable basal insulin with or without metformin; eGFR 30 or more

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed
A1	Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg weekly	basal insulin with or without metformin; lifestyle: not reported	132	132
A2	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg weekly	basal insulin with or without metformin; lifestyle: not reported	132	131
A3	Placebo Placebo	basal insulin with or without metformin; lifestyle: not reported	133	133

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	Placebo A3	Whole trial ALL
age: 18 to 64	n	93	102	86
age: 65 to 84	n	39	29	46
age: 85 or more	n	0	0	1
age	max (years)	84	80	86
age	mean (years)	59.1	58.5	58.8
age	min (years)	28	33	19
age	sd (years)	10.3	9.0	10.9
asian	n	19	23	24
asian	percent	14.4	17.6	18.0
black	n	4	9	8
black	percent	3.0	6.9	6.0
bmi	max (kg/m2)	51.4	51.6	48.8
bmi	mean (kg/m2)	32.8	32.0	31.8
bmi	min (kg/m2)	21.1	19.5	21.0
diabetes duration	max (years)	37.1	36.9	39.6
diabetes duration	mean (years)	12.9	13.7	13.3
diabetes duration	min (years)	0.4	0.6	0.8
egfr: 15 to 30	percent				0.0
egfr: 30 to 60	n				29
egfr: 30 to 60	percent				7.3
egfr: 60 to 90	n				138
egfr: 60 to 90	percent				34.8
egfr: 90 or more	n				229
egfr: 90 or more	percent				57.8
egfr	mean (mL/min/1.73 m2)				90.3
egfr	sd (mL/min/1.73 m2)				18.6
female	n	58	54	62
hba1c	max (percent)	10.3	10.8	11.1
hba1c	mean (percent)	8.4	8.3	8.4
hba1c	min (percent)	7.0	6.9	6.8
hba1c	sd (percent)	0.83	0.82	0.88
insulin dose	mean (IU)	39.3	37.4	36.6
insulin dose	median (IU)	35.00	36.00	36.00
metformin use	n	110	110	110
metformin use	percent	83.3	84.0	82.7
other race other	n	0	1	0
other race other	percent	0.0	0.8	0.0
sbp	mean (mmHg)	134.87	134.40	134.99
sbp	sd (mmHg)	15.00	16.32	16.68
uacr	mean (mg/g)				23.1
weight	max (kg)	162.8	165.6	157.3
weight	mean (kg)	92.7	92.5	89.9
weight	min (kg)	50.4	48.5	47.5
weight	sd (kg)	19.57	22.23	21.06
white	n	108	98	101
white	percent	81.8	74.8	75.9

Analyses this trial contributes to

Results

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

HbA1c change (19 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	final	6.9 percent			132	hypothetical; full analysis; R0012671:Results
30	A1 vs A3	md	-1.93 percent		-2.49 to -1.38		hypothetical; full analysis; region:japan; R0021710:Figure 1
30	A1	change	-1.4 percent			132	hypothetical; full analysis; R0012671:Results
30	A1	change	-1.45 percent	0.09		132	not stated; full analysis; registry:outcomes
30	A1 vs A3	md	-1.35 percent		-1.61 to -1.10		hypothetical; full analysis; R0012671:Results
30	A1	change	-0.88 percent	0.94			not stated; full analysis; hba1c:8_or_less; R0012671:Results
30	A1	change	-1.83 percent	1.00			not stated; full analysis; hba1c:more_than_8; R0012671:Results
30	A2	change	-1.85 percent	0.09		131	not stated; full analysis; registry:outcomes
30	A2	change	-2.19 percent	0.86			not stated; full analysis; hba1c:more_than_8; R0012671:Results
30	A2	final	6.5 percent			131	hypothetical; full analysis; R0012671:Results
30	A2	change	-1.32 percent	0.71			not stated; full analysis; hba1c:8_or_less; R0012671:Results
30	A2 vs A3	md	-2.50 percent		-3.06 to -1.95		hypothetical; full analysis; region:japan; R0021710:Figure 1
30	A2 vs A3	md	-1.75 percent		-2.01 to -1.50		hypothetical; full analysis; R0012671:Results
30	A2	change	-1.8 percent			131	hypothetical; full analysis; R0012671:Results
30	A3	change	-0.04 percent	0.98			not stated; full analysis; hba1c:8_or_less; R0012671:Results
30	A3	change	-0.1 percent			133	hypothetical; full analysis; R0012671:Results
30	A3	final	8.3 percent			133	hypothetical; full analysis; R0012671:Results
30	A3	change	-0.09 percent	0.09		133	not stated; full analysis; registry:outcomes
30	A3	change	-0.28 percent	1.12			not stated; full analysis; hba1c:more_than_8; R0012671:Results

Body weight change in kilograms (diabetes) (22 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-3.7 kg			132	hypothetical; full analysis; R0012671:Results
30	A1 vs A3	md	-2.31 kg		-3.33 to -1.29		hypothetical; full analysis; R0012671:Results
30	A1	change	-3.7 kg			38	hypothetical; full analysis; bmi:25_to_30; R0018825:Figure 1
30	A1 vs A3	md	-2.00 kg		-4.03 to 0.03		hypothetical; full analysis; region:japan; R0021710:Figure 3
30	A1	change	-4.5 kg			10	hypothetical; full analysis; bmi:less_than_25; R0018825:Figure 1
30	A1	change	-3.67 kg	0.36		132	not stated; full analysis; registry:outcomes
30	A1	change	-3.7 kg			41	hypothetical; full analysis; bmi:30_to_35; R0018825:Figure 1
30	A1	change	-3.9 kg			43	hypothetical; full analysis; bmi:35_or_more; R0018825:Figure 1
30	A2 vs A3	md	-5.06 kg		-6.08 to -4.04		hypothetical; full analysis; R0012671:Results
30	A2	change	-6.4 kg			131	hypothetical; full analysis; R0012671:Results
30	A2	change	-6.42 kg	0.36		131	not stated; full analysis; registry:outcomes
30	A2	change	-5.1 kg			36	hypothetical; full analysis; bmi:25_to_30; R0018825:Figure 1
30	A2	change	-6.6 kg			43	hypothetical; full analysis; bmi:30_to_35; R0018825:Figure 1
30	A2	change	-7.5 kg			36	hypothetical; full analysis; bmi:35_or_more; R0018825:Figure 1
30	A2	change	-6.3 kg			16	hypothetical; full analysis; bmi:less_than_25; R0018825:Figure 1
30	A2 vs A3	md	-6.74 kg		-8.68 to -4.81		hypothetical; full analysis; region:japan; R0021710:Figure 3
30	A3	change	-1.4 kg			40	hypothetical; full analysis; bmi:25_to_30; R0018825:Figure 1
30	A3	change	-1.4 kg			133	hypothetical; full analysis; R0012671:Results
30	A3	change	-2.3 kg			37	hypothetical; full analysis; bmi:35_or_more; R0018825:Figure 1
30	A3	change	-1.36 kg	0.37		133	not stated; full analysis; registry:outcomes
30	A3	change	0.4 kg			15	hypothetical; full analysis; bmi:less_than_25; R0018825:Figure 1
30	A3	change	-1.0 kg			41	hypothetical; full analysis; bmi:30_to_35; R0018825:Figure 1

HbA1c below 7 percent (3 lines; O03)

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	61	132	hypothetical; full analysis; R0012671:Results
30	A2	responders	79	131	hypothetical; full analysis; R0012671:Results
30	A3	responders	11	133	hypothetical; full analysis; R0012671:Results

Level 2 or 3 hypoglycemia (participants) (12 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	while on treatment; safety; hypoglycaemia; registry:adverse_events
A1	events	0 / 132	while on treatment; safety; hypoglycaemic unconsciousness; registry:adverse_events
A1	events	11 / 132	not stated; safety; R0012671:Table 2
A1	events	0 / 132	while on treatment; safety; R0021710:Table 2
A2	events	14 / 131	not stated; safety; R0012671:Table 2
A2	events	2 / 131	while on treatment; safety; R0021710:Table 2
A2	events	1 / 131	while on treatment; safety; hypoglycaemia; registry:adverse_events
A2	events	1 / 131	while on treatment; safety; hypoglycaemic unconsciousness; registry:adverse_events
A3	events	0 / 133	while on treatment; safety; hypoglycaemic unconsciousness; registry:adverse_events
A3	events	0 / 133	while on treatment; safety; hypoglycaemia; registry:adverse_events
A3	events	1 / 133	while on treatment; safety; R0021710:Table 2
A3	events	7 / 133	not stated; safety; R0012671:Table 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1 vs A3	rate ratio	2.08		0.67 to 6.51		not stated; safety; R0012671:Results
	A2 vs A3	rate ratio	2.41		0.84 to 6.96		not stated; safety; R0012671:Results

Systolic blood pressure change (8 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-4.29 mmHg	1.26		132	not stated; full analysis; registry:outcomes
30	A1	final	130.5 mmHg			132	hypothetical; full analysis; R0012671:Results
30	A1 vs A3	md	-3.31 mmHg		-6.92 to 0.31		hypothetical; full analysis; R0012671:Results
30	A2	final	127.5 mmHg			131	hypothetical; full analysis; R0012671:Results
30	A2 vs A3	md	-6.29 mmHg		-9.91 to -2.66		hypothetical; full analysis; R0012671:Results
30	A2	change	-7.27 mmHg	1.27		131	not stated; full analysis; registry:outcomes
30	A3	change	-0.99 mmHg	1.34		133	not stated; full analysis; registry:outcomes
30	A3	final	133.8 mmHg			133	hypothetical; full analysis; R0012671:Results

Percent body weight change (2 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-2.90 percent		-3.98 to -1.82		hypothetical; full analysis; R0021710:Figure 3
30	A2 vs A3	md	-5.97 percent		-7.06 to -4.88		hypothetical; full analysis; R0021710:Figure 3

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

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	42	132	hypothetical; full analysis; R0012671:Results
30	A2	responders	66	131	hypothetical; full analysis; R0012671:Results
30	A3	responders	11	133	hypothetical; full analysis; R0012671:Results

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

Week	Arm	Statistic	Estimate	Events / N	Detail
30	A1	responders	9	132	hypothetical; full analysis; R0012671:Results
30	A2	responders	26	131	hypothetical; full analysis; R0012671:Results
30	A3	responders	3	133	hypothetical; full analysis; R0012671:Results

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Table 2
A2	events	0 / 131	not stated; safety; R0012671:Table 2
A3	events	0 / 133	not stated; safety; R0012671:Table 2

Health related quality of life total score (any instrument) (5 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	2.73 points	0.46		132	not stated; full analysis; registry:outcomes
30	A1 vs A3	md	1.48 points		0.14 to 2.82		hypothetical; full analysis; R0012671:Results
30	A2 vs A3	md	2.22 points		0.87 to 3.56		hypothetical; full analysis; R0012671:Results
30	A2	change	3.47 points	0.46		131	not stated; full analysis; registry:outcomes
30	A3	change	1.25 points	0.50		133	not stated; full analysis; registry:outcomes

Serious adverse events (3 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	8 / 132	not stated; safety; R0012671:Table 2
A2	events	12 / 131	not stated; safety; R0012671:Table 2
A3	events	9 / 133	not stated; safety; R0012671:Table 2

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	6 / 132	not stated; safety; R0012671:Table 2
A2	events	8 / 131	not stated; safety; R0012671:Table 2
A3	events	1 / 133	not stated; safety; R0012671:Table 2

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	15 / 132	not stated; safety; R0012671:Table 2
A2	events	22 / 131	not stated; safety; R0012671:Table 2
A3	events	6 / 133	not stated; safety; R0012671:Table 2

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	8 / 132	not stated; safety; R0012671:Table 2
A2	events	15 / 131	not stated; safety; R0012671:Table 2
A3	events	4 / 133	not stated; safety; R0012671:Table 2

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	6 / 132	not stated; safety; R0012671:Table 2
A2	events	9 / 131	not stated; safety; R0012671:Table 2
A3	events	2 / 133	not stated; safety; R0012671:Table 2

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

Arm	Statistic	Events / N	Detail
A1	events	3 / 132	while on treatment; safety; R0021710:Table 2
A2	events	6 / 131	while on treatment; safety; R0021710:Table 2
A3	events	0 / 133	while on treatment; safety; R0021710:Table 2

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	3 / 132	not stated; safety; R0012671:Table 2
A1	events	0 / 132	while on treatment; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 131	while on treatment; safety; cholecystitis acute; registry:adverse_events
A2	events	1 / 131	not stated; safety; R0012671:Table 2
A3	events	0 / 133	while on treatment; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 133	not stated; safety; R0012671:Table 2

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Results
A1	events	1 / 132	not stated; safety; R0012671:Results
A2	events	0 / 131	not stated; safety; R0012671:Results
A3	events	0 / 133	not stated; safety; R0012671:Results

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Results
A2	events	0 / 131	not stated; safety; R0012671:Results
A3	events	0 / 133	not stated; safety; R0012671:Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Results
A2	events	0 / 131	not stated; safety; R0012671:Results
A3	events	0 / 133	not stated; safety; R0012671:Results

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	3.0	132	not stated; safety; R0012671:Results
A2	events	0.8	131	not stated; safety; R0012671:Results
A3	events		0 / 133	not stated; safety; R0012671:Results

Death by suicide (3 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Table 2
A2	events	0 / 131	not stated; safety; R0012671:Table 2
A3	events	0 / 133	not stated; safety; R0012671:Table 2

Pancreatic cancer (3 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 132	not stated; safety; R0012671:Table 2
A2	events	0 / 131	not stated; safety; R0012671:Table 2
A3	events	0 / 133	not stated; safety; R0012671:Table 2

Any cancer (3 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	1 / 132	not stated; safety; R0012671:Table 2
A2	events	0 / 131	not stated; safety; R0012671:Table 2
A3	events	0 / 133	not stated; safety; R0012671:Table 2