parallel randomized trial

STEP 5

Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

Overweight or obesity without diabetes (adults)NCT03693430S000214

Design

Randomized: 304
Start year: 2018
Treatment: 104 weeks, follow-up 111 weeks
Countries: Canada, Italy, Hungary, Spain, United States (41 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; HbA1c below 6.5 percent

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 2.4 mg subcutaneous once weekly Semaglutide 2.4 mg	reduced calorie diet and physical activity counseling every 4 weeks; lifestyle: standard	152	152
A2	Placebo Placebo	reduced calorie diet and physical activity counseling every 4 weeks; lifestyle: standard	152	152

Baseline characteristics

As printed in the trial reports or registry, per arm or for the whole trial.

Characteristic	Statistic	Semaglutide 2.4 mg subcutaneous once weekly A1	Placebo A2
age	mean (years)	47.3	47.4
age	sd (years)	11.7	10.3
asian	n	2	0
asian	percent	1.3	0.0
black	n	7	5
black	percent	4.6	3.3
bmi	mean (kg/m2)	38.6	38.5
bmi	sd (kg/m2)	6.7	7.2
egfr	mean (mL/min/1.73 m2)	95.7	92.9
established cvd: coronary artery disease	n	2	3
established cvd: coronary artery disease	percent	1.3	2.0
female	n	123	113
female	percent	80.9	74.3
hba1c	mean (percent)	5.7	5.7
hba1c	sd (percent)	0.3	0.4
hispanic	n	18	21
hispanic	percent	11.8	13.8
other coronary artery disease	n	2	3
other coronary artery disease	percent	1.3	2.0
other hypertension	n	56	62
other hypertension	percent	36.8	40.8
other prediabetes	n	77	64
other prediabetes	percent	50.7	42.1
other race american indian alaska native	n	2	1
other race american indian alaska native	percent	1.3	0.7
other race other	n	0	4
other race other	percent	0.0	2.6
sbp	mean (mmHg)	126	125
sbp	sd (mmHg)	14	15
waist	mean (cm)	115.8	115.7
waist	sd (cm)	14.3	15.5
weight	mean (kg)	105.6	106.5
weight	sd (kg)	20.8	23.1
white	n	141	142
white	percent	92.8	93.4

Analyses this trial contributes to

Results

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

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
104	A1	change	-5.7 mmHg	1.1		152	treatment policy; full analysis; R0021896:Table 2
104	A1	change	-6 mmHg	13		142	not stated; full analysis; registry:outcomes
104	A1 vs A2	md	-4.2 mmHg		-7.3 to -1.0		treatment policy; full analysis; R0021896:Table 2
104	A2	change	-1.6 mmHg	1.2		152	treatment policy; full analysis; R0021896:Table 2
104	A2	change	-1 mmHg	15		125	not stated; full analysis; registry:outcomes

Percent body weight change (13 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	percent change	-15.8 percent	9.3		149	not stated; full analysis; registry:outcomes
52	A1	percent change	-15.6 percent	0.7		152	treatment policy; full analysis; R0021896:Table 2
52	A1 vs A2	md	-12.6 percent		-14.5 to -10.7		treatment policy; full analysis; R0021896:Table 2
52	A2	percent change	-3.0 percent	0.7		152	treatment policy; full analysis; R0021896:Table 2
52	A2	percent change	-3.3 percent	6.4		129	not stated; full analysis; registry:outcomes
104	A1 vs A2	md	-12.6 percent		-15.3 to -9.8		treatment policy; full analysis; R0021896:Table 2
104	A1	percent change	-16.7 percent	0.9		152	hypothetical; full analysis; R0021896:Results
104	A1 vs A2	md	-16.0 percent		-18.6 to -13.5		hypothetical; full analysis; R0021896:Results
104	A1	percent change	-15.2 percent	0.9		152	treatment policy; full analysis; R0021896:Table 2
104	A1	percent change	-15.9 percent	12.3		144	treatment policy; full analysis; registry:outcomes
104	A2	percent change	-1.9 percent	8.9		128	treatment policy; full analysis; registry:outcomes
104	A2	percent change	-2.6 percent	1.1		152	treatment policy; full analysis; R0021896:Table 2
104	A2	percent change	-0.6 percent	0.9		152	hypothetical; full analysis; R0021896:Results

Weight loss of 5 percent or more (8 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders			132 / 149	not stated; full analysis; registry:outcomes
52	A2	responders			38 / 129	not stated; full analysis; registry:outcomes
104	A1 vs A2	or	18.1	10.0 to 32.5		hypothetical; full analysis; R0021896:Results
104	A1	responders			110 / 132	hypothetical; full analysis; R0021896:Results
104	A1	responders			111 / 144	treatment policy; full analysis; R0021896:Table 2
104	A1 vs A2	or	5.0	3.0 to 8.4		treatment policy; full analysis; R0021896:Table 2
104	A2	responders			38 / 109	hypothetical; full analysis; R0021896:Results
104	A2	responders			44 / 128	treatment policy; full analysis; R0021896:Table 2

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders			102 / 149	not stated; full analysis; registry:outcomes
52	A2	responders			17 / 129	not stated; full analysis; registry:outcomes
104	A1	responders			89 / 144	treatment policy; full analysis; R0021896:Table 2
104	A1 vs A2	or	7.2	4.0 to 13.2		treatment policy; full analysis; R0021896:Table 2
104	A2	responders			17 / 128	treatment policy; full analysis; R0021896:Table 2

Weight loss of 15 percent or more (5 lines; O11C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders			78 / 149	not stated; full analysis; registry:outcomes
52	A2	responders			7 / 129	not stated; full analysis; registry:outcomes
104	A1	responders			75 / 144	treatment policy; full analysis; R0021896:Table 2
104	A1 vs A2	or	9.4	4.4 to 20.0		treatment policy; full analysis; R0021896:Table 2
104	A2	responders			9 / 128	treatment policy; full analysis; R0021896:Table 2

Weight loss of 20 percent or more (5 lines; O11D)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders			52 / 149	not stated; full analysis; registry:outcomes
52	A2	responders			3 / 129	not stated; full analysis; registry:outcomes
104	A1 vs A2	or	12.8	3.9 to 41.9		treatment policy; full analysis; R0021896:Table 2
104	A1	responders			52 / 144	treatment policy; full analysis; R0021896:Table 2
104	A2	responders			3 / 128	treatment policy; full analysis; R0021896:Table 2

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 152	while on treatment; safety; acute renal failure; R0021896:Table 3
	A2	events				0 / 152	while on treatment; safety; acute renal failure; R0021896:Table 3

Progression to type 2 diabetes (4 lines; O14)

Arm	Statistic	Events / N	Detail
A1	events	0 / 74	not stated; full analysis; glycemic_status:prediabetes; R0021896:Table 2
A1	events	0 / 71	not stated; full analysis; glycemic_status:normoglycemia; R0021896:Table 2
A2	events	1 / 77	not stated; full analysis; glycemic_status:normoglycemia; R0021896:Table 2
A2	events	2 / 54	not stated; full analysis; glycemic_status:prediabetes; R0021896:Table 2

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 152	treatment policy; safety; R0021896:Table 3
	A2	events				0 / 152	treatment policy; safety; R0021896:Table 3

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				12 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				18 / 152	while on treatment; safety; R0021896:Table 3

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				9 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				7 / 152	while on treatment; safety; R0021896:Table 3

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				81 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				33 / 152	while on treatment; safety; R0021896:Table 3

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				46 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				7 / 152	while on treatment; safety; R0021896:Table 3

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				53 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				36 / 152	while on treatment; safety; R0021896:Table 3

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				47 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				17 / 152	while on treatment; safety; R0021896:Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				6 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				1 / 152	while on treatment; safety; R0021896:Table 3

Gallbladder and biliary disease (5 lines; O28)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			4 / 152	while on treatment; safety; R0021896:Table 3
A1	events			3 / 152	while on treatment; safety; cholelithiasis; R0021896:Table 3
A1 vs A2	rr	2.00	0.37 to 10.76		not stated; safety; R0013578:Table 1
A2	events			2 / 152	while on treatment; safety; cholelithiasis; R0021896:Table 3
A2	events			2 / 152	while on treatment; safety; R0021896:Table 3

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 152	while on treatment; safety; R0021896:Table 3
	A2	events				0 / 152	while on treatment; safety; R0021896:Table 3

Suicidal ideation or behavior (2 lines; O35A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 152	treatment policy; safety; R0019370:Table 3
	A2	events				2 / 146	treatment policy; safety; R0019370:Table 3

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 152	treatment policy; safety; R0021896:Table 3
	A2	events				4 / 152	treatment policy; safety; R0021896:Table 3