parallel randomized trial

STEP 1

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

Overweight or obesity without diabetes (adults)NCT03548935S000144

Design

Randomized: 1,961
Start year: 2018
Treatment: 68 weeks, follow-up 75 weeks
Countries: multinational (129 sites)
Sponsor: Novo Nordisk (industry)
Eligibility: adults; BMI 30 or more, or 27 or more with a weight related condition; no diabetes; HbA1c below 6.5 percent

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
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	lifestyle: standard	1,306	1,306
A2	Placebo Placebo	lifestyle: standard	655	655

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)	46	47
age	sd (years)	13	12
asian	n	181	80
asian	percent	13.9	12.2
black	n	72	39
black	percent	5.5	6.0
bmi: 30 to less than 35	n	436	207
bmi: 30 to less than 35	percent	33.4	31.6
bmi: 35 to less than 40	n	406	208
bmi: 35 to less than 40	percent	31.1	31.8
bmi: 40 or more	n	383	204
bmi: 40 or more	percent	29.3	31.1
bmi: less than 30	n	81	36
bmi: less than 30	percent	6.2	5.5
bmi	mean (kg/m2)	37.8	38.0
bmi	sd (kg/m2)	6.7	6.5
egfr	mean (mL/min/1.73 m2)	96.3	95.9
established cvd: coronary artery disease	n	32	17
established cvd: coronary artery disease	percent	2.5	2.6
female	n	955	498
female	percent	73.1	76.0
hba1c	mean (percent)	5.7	5.7
hba1c	sd (percent)	0.3	0.3
hispanic	n	150	86
hispanic	percent	11.5	13.1
other race other	n	80	37
other race other	percent	6.1	5.6
sbp	mean (mmHg)	126	127
sbp	sd (mmHg)	14	14
waist	mean (cm)	114.6	114.8
waist	sd (cm)	14.8	14.4
weight	mean (kg)	105.4	105.2
weight	sd (kg)	22.1	21.5
white	n	973	499
white	percent	74.5	76.2

Analyses this trial contributes to

Results

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

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	-7 mmHg	14		1210	treatment policy; full analysis; registry:outcomes
68	A1	change	-6.16 mmHg			1306	treatment policy; full analysis; R0023399:Table 2
68	A1 vs A2	md	-5.10 mmHg		-6.34 to -3.87		treatment policy; full analysis; R0023399:Table 2
68	A2	change	-1.06 mmHg			655	treatment policy; full analysis; R0023399:Table 2
68	A2	change	-1 mmHg	13		574	treatment policy; full analysis; registry:outcomes
120	A1	final	131 mmHg	15		197	not stated; other; R0022757:Table 2
120	A2	final	132 mmHg	15		93	not stated; other; R0022757:Table 2

Percent body weight change (12 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1 vs A2	md	-12.44 percent		-13.37 to -11.51		treatment policy; full analysis; R0023399:Table 2
68	A1	percent change	-16.9 percent				hypothetical; full analysis; R0023399:p6
68	A1 vs A2	md	-14.4 percent		-15.3 to -13.5		hypothetical; full analysis; R0023399:Results
68	A1	percent change	-14.85 percent			1306	treatment policy; full analysis; R0023399:Table 2
68	A1	percent change	-15.6 percent	10.1		1306	treatment policy; full analysis; registry:outcomes
68	A1	percent change	-16.9 percent	9.4		1306	while on treatment; full analysis; registry:outcomes
68	A2	percent change	-2.41 percent			655	treatment policy; full analysis; R0023399:Table 2
68	A2	percent change	-2.8 percent	6.5		655	treatment policy; full analysis; registry:outcomes
68	A2	percent change	-2.4 percent				hypothetical; full analysis; R0023399:p6
68	A2	percent change	-3.1 percent	6.4		655	while on treatment; full analysis; registry:outcomes
120	A1	percent change	-5.6 percent	8.9		197	not stated; other; R0022757:Results
120	A2	percent change	-0.1 percent	5.8		93	not stated; other; R0022757:Results

Weight loss of 5 percent or more (10 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
68	A1	responders			978 / 1306	while on treatment; full analysis; registry:outcomes
68	A1 vs A2	or	37.03	28.02 to 48.95		not stated; full analysis; registry:outcomes
68	A1	responders			1047 / 1212	treatment policy; full analysis; R0023399:p7
68	A1 vs A2	or	11.2	8.9 to 14.2		treatment policy; full analysis; R0023399:Table 2
68	A1	responders	92.4		1059	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders			182 / 577	treatment policy; full analysis; R0023399:p7
68	A2	responders	33.1		499	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders			165 / 655	while on treatment; full analysis; registry:outcomes
120	A1	responders			95 / 197	not stated; other; R0022757:Results
120	A2	responders			21 / 93	not stated; other; R0022757:Results

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
68	A1 vs A2	or	14.7	11.1 to 19.4		treatment policy; full analysis; R0023399:Table 2
68	A1	responders			838 / 1212	treatment policy; full analysis; R0023399:p7
68	A1	responders	74.8		1059	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders	11.8		499	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders			69 / 577	treatment policy; full analysis; R0023399:p7

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
68	A1 vs A2	or	19.3	12.9 to 28.8		treatment policy; full analysis; R0023399:Table 2
68	A1	responders			612 / 1212	treatment policy; full analysis; R0023399:p7
68	A1	responders	54.8		1059	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders	5.0		499	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders			28 / 577	treatment policy; full analysis; R0023399:p7

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
68	A1	responders			388 / 1212	treatment policy; full analysis; R0023399:p7
68	A1 vs A2	or	26.9	14.2 to 51.0		treatment policy; full analysis; R0023399:Table 2
68	A1	responders	34.8		1059	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders	2.0		499	while on treatment; full analysis; R0023399:Figure 1D
68	A2	responders			10 / 577	treatment policy; full analysis; R0023399:p7

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 1306	while on treatment; safety; R0023399:Table 3
	A2	events				2 / 655	while on treatment; safety; R0023399:Table 3

Progression to type 2 diabetes (4 lines; O14)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		2 / 120	not stated; other; glycemic_status:prediabetes; R0022757:Figure 3
A1	events	0.5	554	treatment policy; other; glycemic_status:prediabetes; R0021798:Figure 1A
A2	events	3.0	230	treatment policy; other; glycemic_status:prediabetes; R0021798:Figure 1A
A2	events		3 / 47	not stated; other; glycemic_status:prediabetes; R0022757:Figure 3

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 1306	treatment policy; safety; R0023399:Table 3
	A2	events				1 / 655	treatment policy; safety; R0023399:Table 3

SF-36 physical component summary change (2 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	2.4 points	6.7		1195	treatment policy; full analysis; registry:outcomes
68	A2	change	0.2 points	7.1		566	treatment policy; full analysis; registry:outcomes

Physical functioning (any instrument) (10 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	14.67 points			1306	treatment policy; full analysis; R0023399:Table 2
68	A1 vs A2	md	1.80 points		1.18 to 2.42		treatment policy; full analysis; R0023399:Table 2
68	A1	change	15.0 points	21.6		1193	treatment policy; full analysis; registry:outcomes
68	A1	change	2.21 points			1306	treatment policy; full analysis; R0023399:Table 2
68	A1	change	2.3 points	6.6		1195	treatment policy; full analysis; registry:outcomes
68	A1 vs A2	md	9.43 points		7.50 to 11.35		treatment policy; full analysis; R0023399:Table 2
68	A2	change	0.41 points			655	treatment policy; full analysis; R0023399:Table 2
68	A2	change	5.25 points			655	treatment policy; full analysis; R0023399:Table 2
68	A2	change	6.0 points	21.1		566	treatment policy; full analysis; registry:outcomes
68	A2	change	0.4 points	7.4		566	treatment policy; full analysis; registry:outcomes

Health related quality of life total score (any instrument) (2 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
68	A1	change	16.2 points	17.8		1193	treatment policy; full analysis; registry:outcomes
68	A2	change	6.3 points	16.8		566	treatment policy; full analysis; registry:outcomes

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				128 / 1306	while on treatment; safety; R0023399:Table 3
	A2	events				42 / 655	while on treatment; safety; R0023399:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 1306	not stated; randomized; registry:flow
A1	events	92 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; randomized; registry:flow
A2	events	20 / 655	while on treatment; safety; R0023399:Table 3

Nausea (5 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 1306	not stated; safety; registry:adverse_events
A1	events	576 / 1306	not stated; safety; registry:adverse_events
A1	events	577 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	114 / 655	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; registry:adverse_events

Vomiting (5 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	4 / 1306	not stated; safety; registry:adverse_events
A1	events	321 / 1306	not stated; safety; registry:adverse_events
A1	events	324 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; registry:adverse_events
A2	events	43 / 655	while on treatment; safety; R0023399:Table 3

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	412 / 1306	while on treatment; safety; R0023399:Table 3
A1	events	411 / 1306	not stated; safety; registry:adverse_events
A1	events	1 / 1306	not stated; safety; registry:adverse_events
A2	events	104 / 655	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; registry:adverse_events

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	305 / 1306	not stated; safety; registry:adverse_events
A1	events	1 / 1306	not stated; safety; registry:adverse_events
A1	events	306 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; registry:adverse_events
A2	events	62 / 655	while on treatment; safety; R0023399:Table 3

Discontinuation due to gastrointestinal adverse events (4 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 1306	not stated; randomized; registry:flow
A1	events	59 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; randomized; registry:flow
A2	events	5 / 655	while on treatment; safety; R0023399:Table 3

Gallbladder and biliary disease (12 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	3 / 1306	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	4 / 1306	not stated; safety; cholecystitis; registry:adverse_events
A1	events	12 / 1306	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 1306	not stated; safety; bile duct stone; registry:adverse_events
A1	events	23 / 1306	while on treatment; safety; cholelithiasis; R0023399:Table 3
A1	events	34 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; cholecystitis; registry:adverse_events
A2	events	1 / 655	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	8 / 655	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	4 / 655	while on treatment; safety; cholelithiasis; R0023399:Table 3
A2	events	0 / 655	not stated; safety; bile duct stone; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	2 / 1306	not stated; safety; registry:adverse_events
A1	events	3 / 1306	while on treatment; safety; R0023399:Table 3
A2	events	0 / 655	not stated; safety; registry:adverse_events
A2	events	0 / 655	while on treatment; safety; R0023399:Table 3

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 1306	not stated; safety; papillary thyroid cancer; registry:adverse_events
	A2	events				0 / 655	not stated; safety; papillary thyroid cancer; registry:adverse_events

Nonarteritic anterior ischemic optic neuropathy (2 lines; O34)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 1306	not stated; safety; optic ischaemic neuropathy; registry:adverse_events
	A2	events				0 / 655	not stated; safety; optic ischaemic neuropathy; registry:adverse_events

Suicidal ideation or behavior (4 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 1306	not stated; safety; suicidal ideation; registry:adverse_events
A1	events	0 / 1306	not stated; safety; suicide attempt; registry:adverse_events
A2	events	0 / 655	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	1 / 655	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 1306	treatment policy; safety; R0023399:Table 3
	A2	events				0 / 655	treatment policy; safety; R0023399:Table 3

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				14 / 1306	treatment policy; safety; R0023399:Table 3
	A2	events				7 / 655	treatment policy; safety; R0023399:Table 3