parallel randomized trial

SURMOUNT-OSA

A Master Protocol to Investigate the Efficacy and Safety of Tirzepatide Once Weekly in Participants Who Have Obstructive Sleep Apnea and Obesity: A Randomized, Double-Blind, Placebo-Controlled Trial

Overweight or obesity without diabetes (adults)Obstructive sleep apnea NCT05412004S000156

Design

Randomized: 469
Start year: 2022
Treatment: 52 weeks, follow-up 56 weeks
Countries: Australia, Brazil, China, Czech Republic, Germany, Japan, Mexico, Taiwan, United States (60 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults; AHI 15 or more; BMI 30 or more (27 in Japan); no diabetes

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: modified itt
Missing data: multiple imputation

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg Tirzepatide MTD, trial 1 (no PAP)	no PAP therapy; lifestyle: standard	114	114	97
A2	Placebo Placebo, trial 1 (no PAP)	no PAP therapy; lifestyle: standard	120	120	84
A3	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg Tirzepatide MTD, trial 2 (on PAP)	PAP therapy; lifestyle: standard	120	119	108
A4	Placebo Placebo, trial 2 (on PAP)	PAP therapy; lifestyle: standard	115	114	85

Baseline characteristics

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

Characteristic	Statistic	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg A1	Placebo A2	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg A3	Placebo A4
age: 50 or older	n	51	58	66	70
age: 50 or older	percent	44.7	48.3	55.0	60.9
age: less than 50	n	63	62	54	45
age: less than 50	percent	55.3	51.7	45.0	39.1
age	mean (years)	47.3	48.4	50.8	52.7
age	sd (years)	11.0	11.9	10.7	11.3
ahi: 15 to less than 30	n	39	43	35	37
ahi: 15 to less than 30	percent	34.2	36.1	29.4	32.5
ahi: 30 or more	n	74	73	84	75
ahi: 30 or more	percent	64.9	61.3	70.6	65.8
ahi: less than 15	n	1	2	0	2
ahi: less than 15	percent	0.9	1.7		1.8
ahi: no apnea	n	0	1
ahi: no apnea	percent		0.8
ahi	mean (events per hour)	52.9	50.1	46.1	53.1
ahi	sd (events per hour)	30.5	31.5	22.4	30.2
asian	n	23	24	17	16
asian	percent	20.2	20.0	14.2	14.0
black	n	6	7	8	3
black	percent	5.3	5.8	6.7	2.6
bmi: 35 to less than 40	n	39	35	47	41
bmi: 35 to less than 40	percent	34.2	29.2	39.5	36.0
bmi: 40 or more	n	42	41	39	40
bmi: 40 or more	percent	36.8	34.2	32.8	35.1
bmi: less than 35	n	33	44	33	33
bmi: less than 35	percent	28.9	36.7	27.7	28.9
bmi	mean (kg/m2)	39.7	38.6	38.6	38.7
bmi	sd (kg/m2)	7.3	6.7	6.1	6.0
female	n	36	41	33	32
female	percent	31.6	34.2	27.5	27.8
hba1c	mean (percent)	5.69	5.64	5.62	5.65
hba1c	sd (percent)	0.37	0.35	0.37	0.44
hispanic	n	51	47	38	38
hispanic	percent	44.7	39.2	31.7	33.0
other race american indian alaska native	n	9	9	10	9
other race american indian alaska native	percent	7.9	7.5	8.3	7.9
other race multiple	n	2	0	0	0
other race multiple	percent	1.8
other race native hawaiian pacific islander	n	0	0	0	0
sbp	mean (mmHg)	128.4	130.3	130.5	130.5
sbp	sd (mmHg)	12.2	10.7	14.3	12.8
waist	mean (cm)	122.6	119.8	120.7	121.0
waist	sd (cm)	16.6	14.8	13.1	14.0
weight	mean (kg)	116.7	112.8	115.8	115.1
weight	sd (kg)	24.6	22.6	21.5	22.7
white	n	74	80	85	86
white	percent	64.9	66.7	70.8	75.4

Results

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

Systolic blood pressure change (18 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
48	A1	change	-9.6 mmHg	1.1			hypothetical; modified itt; R0016217:Table 2
48	A1	change	-9.5 mmHg		-11.5 to -7.5	114	treatment policy; modified itt; R0018977:Table 2
48	A1 vs A2	md	-7.6 mmHg		-10.5 to -4.8		treatment policy; modified itt; R0018977:Table 2
48	A1 vs A2	md	-7.9 mmHg		-11.0 to -4.9		hypothetical; modified itt; R0016217:Table 2
48	A2	change	-1.8 mmHg		-3.9 to 0.2	120	treatment policy; modified itt; R0018977:Table 2
48	A2	change	-1.7 mmHg	1.1			hypothetical; modified itt; R0016217:Table 2
48	A3	change	-7.6 mmHg	1.1			hypothetical; modified itt; R0016217:Table 2
48	A3	change	-7.6 mmHg		-9.7 to -5.6	120	treatment policy; modified itt; R0018977:Table 2
48	A3 vs A4	md	-4.3 mmHg		-7.3 to -1.2		hypothetical; modified itt; R0016217:Table 2
48	A3 vs A4	md	-3.7 mmHg		-6.8 to -0.7		treatment policy; modified itt; R0018977:Table 2
48	A4	change	-3.9 mmHg		-6.3 to -1.6	115	treatment policy; modified itt; R0018977:Table 2
48	A4	change	-3.3 mmHg	1.2			hypothetical; modified itt; R0016217:Table 2
52	A1 vs A2	md	-6.8 mmHg		-9.6 to -4.0		hypothetical; modified itt; R0005976:Supplement Table S2
52	A1	change	-9.7 mmHg	0.97			hypothetical; modified itt; R0005976:Supplement Table S2
52	A2	change	-2.9 mmHg	1.04			hypothetical; modified itt; R0005976:Supplement Table S2
52	A3	change	-8.7 mmHg	1.01			hypothetical; modified itt; R0005976:Supplement Table S2
52	A3 vs A4	md	-7.2 mmHg		-10.2 to -4.2		hypothetical; modified itt; R0005976:Supplement Table S2
52	A4	change	-1.6 mmHg	1.13			hypothetical; modified itt; R0005976:Supplement Table S2

Percent body weight change (102 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
20	A1	percent change	-11.00 percent	0.44			hypothetical; modified itt; R0011011:Table 2
20	A1 vs A2	md	-8.8 percent		-10.1 to -7.6		hypothetical; modified itt; R0011011:Results
20	A2	percent change	-2.20 percent	0.45			hypothetical; modified itt; R0011011:Table 2
20	A3	percent change	-12.60 percent	0.44			hypothetical; modified itt; R0011011:Table 2
20	A3 vs A4	md	-10.0 percent		-11.3 to -8.8		hypothetical; modified itt; R0011011:Results
20	A4	percent change	-2.60 percent	0.46			hypothetical; modified itt; R0011011:Table 2
24	A1	percent change	-12.80 percent	0.49			hypothetical; modified itt; R0011011:Table 2
24	A2	percent change	-2.30 percent	0.50			hypothetical; modified itt; R0011011:Table 2
24	A3	percent change	-14.50 percent	0.49			hypothetical; modified itt; R0011011:Table 2
24	A4	percent change	-2.30 percent	0.52			hypothetical; modified itt; R0011011:Table 2
36	A1	percent change	-15.90 percent	0.59			hypothetical; modified itt; R0011011:Table 2
36	A2	percent change	-2.20 percent	0.61			hypothetical; modified itt; R0011011:Table 2
36	A3	percent change	-17.80 percent	0.64			hypothetical; modified itt; R0011011:Table 2
36	A4	percent change	-2.50 percent	0.68			hypothetical; modified itt; R0011011:Table 2
48	A1	percent change	-17.60 percent	0.68			hypothetical; modified itt; R0011011:Table 2
48	A2	percent change	-1.90 percent	0.71			hypothetical; modified itt; R0011011:Table 2
48	A3	percent change	-19.40 percent	0.72			hypothetical; modified itt; R0011011:Table 2
48	A4	percent change	-2.30 percent	0.77			hypothetical; modified itt; R0011011:Table 2
52	A1	percent change	-17.2 percent	1.02			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A1	percent change	-16.3 percent	1.39			hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A1 vs A2	md	-14.6 percent		-18.5 to -10.7		hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A1	percent change	-19.0 percent	0.80			hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A1 vs A2	md	-17.7 percent		-20.1 to -15.4		hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A1	percent change	-18.10 percent	0.71			hypothetical; modified itt; R0011011:Table 2
52	A1 vs A2	md	-16.8 percent		-18.8 to -14.7		hypothetical; modified itt; R0011011:Results
52	A1	percent change	-17.7 percent		-19.0 to -16.3	114	treatment policy; modified itt; R0018977:Table 2
52	A1 vs A2	md	-16.1 percent		-18.0 to -14.2		treatment policy; modified itt; R0018977:Table 2
52	A1	percent change	-18.8 percent	1.04			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A1 vs A2	md	-16.8 percent		-19.6 to -13.9		hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A1	percent change	-18.7 percent			7	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A1 vs A2	md	-17.1 percent		-23.3 to -10.9		hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A1	percent change	-17.6 percent	0.97			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A1 vs A2	md	-16.8 percent		-19.7 to -13.9		hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A1	percent change	-18.2 percent			105	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A1 vs A2	md	-16.9 percent		-19.0 to -14.8		hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A1	percent change	-18.4 percent	1.26			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A1 vs A2	md	-16.1 percent		-19.7 to -12.5		hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A1	percent change	-18.9 percent	1.07			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A1 vs A2	md	-19.8 percent		-22.9 to -16.7		hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A1	percent change	-16.9 percent	1.34			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A1 vs A2	md	-13.6 percent		-17.6 to -9.6		hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A1 vs A2	md	-16.0 percent		-20.3 to -11.7		hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A1 vs A2	md	-16.5 percent		-19.3 to -13.6		hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A1	percent change	-20.2 percent	0.96			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A1 vs A2	md	-17.8 percent		-20.7 to -15.0		hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A1	percent change	-17.0 percent	1.46			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A2	percent change	-2.4 percent	1.03			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A2	percent change	-3.3 percent	1.46			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A2	percent change	-2.0 percent	0.99			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A2	percent change	-0.7 percent	1.01			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A2	percent change	-1.6 percent	1.37			hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A2	percent change	-1.30 percent	0.73			hypothetical; modified itt; R0011011:Table 2
52	A2	percent change	-2.3 percent	1.26			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A2	percent change	-1.2 percent	0.85			hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A2	percent change	-1.6 percent			12	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A2	percent change	-1.6 percent		-2.9 to -0.2	120	treatment policy; modified itt; R0018977:Table 2
52	A2	percent change	-1.0 percent	1.58			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A2	percent change	0.9 percent	1.12			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A2	percent change	-1.3 percent			103	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A2	percent change	-0.7 percent	1.09			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A3 vs A4	md	-16.3 percent		-19.5 to -13.2		hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A3 vs A4	md	-17.8 percent		-19.9 to -15.7		hypothetical; modified itt; R0011011:Results
52	A3 vs A4	md	-18.6 percent		-23.0 to -14.2		hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A3	percent change	-19.6 percent		-21.0 to -18.2	120	treatment policy; modified itt; R0018977:Table 2
52	A3 vs A4	md	-17.3 percent		-19.3 to -15.3		treatment policy; modified itt; R0018977:Table 2
52	A3	percent change	-20.10 percent	0.73			hypothetical; modified itt; R0011011:Table 2
52	A3	percent change	-19.9 percent	0.98			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A3 vs A4	md	-16.8 percent		-19.6 to -14.0		hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A3	percent change	-19.6 percent	1.88			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A3 vs A4	md	-16.9 percent		-21.7 to -12.2		hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A3	percent change	-20.6 percent			12	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A3 vs A4	md	-15.2 percent		-19.7 to -10.8		hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A3 vs A4	md	-16.4 percent		-18.9 to -13.8		hypothetical; modified itt; sex:male; R0005976:Supplement Table S11
52	A3	percent change	-18.9 percent	0.87			hypothetical; modified itt; sex:male; R0005976:Supplement Table S11
52	A3	percent change	-20.5 percent	1.08			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A3	percent change	-20.3 percent	1.11			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A3 vs A4	md	-19.0 percent		-22.3 to -15.6		hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A3 vs A4	md	-21.4 percent		-25.0 to -17.9		hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A3 vs A4	md	-17.3 percent		-20.5 to -14.1		hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A3	percent change	-20.0 percent			106	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A3 vs A4	md	-18.2 percent		-20.6 to -15.9		hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A3	percent change	-23.1 percent	1.23			hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A3	percent change	-19.0 percent	1.22			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15
52	A3 vs A4	md	-17.9 percent		-21.4 to -14.4		hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15
52	A3	percent change	-21.8 percent	1.35			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A3 vs A4	md	-20.3 percent		-24.2 to -16.5		hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A3	percent change	-20.8 percent	1.51			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A3	percent change	-19.2 percent	0.95			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A4	percent change	-2.7 percent	1.46			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A4	percent change	-2.30 percent	0.78			hypothetical; modified itt; R0011011:Table 2
52	A4	percent change	-2.3 percent		-3.8 to -0.9	115	treatment policy; modified itt; R0018977:Table 2
52	A4	percent change	-3.1 percent	1.00			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A4	percent change	-5.4 percent			19	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A4	percent change	-1.3 percent	1.28			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A4	percent change	-1.8 percent			94	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A4	percent change	-1.5 percent	1.39			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A4	percent change	-2.9 percent	1.26			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A4	percent change	-1.1 percent	1.25			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15
52	A4	percent change	-3.2 percent	1.21			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A4	percent change	-2.2 percent	1.61			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A4	percent change	-1.7 percent	1.29			hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A4	percent change	-2.5 percent	0.95			hypothetical; modified itt; sex:male; R0005976:Supplement Table S11

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; registry:adverse_events
A2	events	0 / 120	not stated; safety; registry:adverse_events
A3	events	1 / 119	not stated; safety; registry:adverse_events
A4	events	0 / 114	not stated; safety; registry:adverse_events

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; R0018977:Table 4

Three point MACE (3 lines; O21)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4

Four point MACE including unstable angina (7 lines; O21B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A4	events	1 / 114	not stated; safety; R0018977:Table 4

Hospitalization for heart failure (3 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4

SF-36 physical component summary change (1 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
20	A1 vs A2	md	2.2 points		0.5 to 3.9		treatment policy; modified itt; R0016265:Results

Physical functioning (any instrument) (1 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
20	A1 vs A2	md	2.1 points		0.5 to 3.7		treatment policy; modified itt; R0016265:Results

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	0.04 points		0.00 to 0.08		treatment policy; modified itt; R0016265:Results
52	A3 vs A4	md	0.05 points		0.01 to 0.09		treatment policy; modified itt; R0016265:Results

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	9 / 114	not stated; safety; R0018977:Table 4
A2	events	7 / 120	not stated; safety; R0018977:Table 4
A3	events	7 / 119	not stated; safety; R0018977:Table 4
A4	events	12 / 114	not stated; safety; R0018977:Table 4

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	5 / 114	not stated; safety; R0018977:Table 4
A1	events	0 / 114	not stated; randomized; R0018977:Supplement Figure S3
A2	events	2 / 120	not stated; randomized; R0018977:Supplement Figure S3
A2	events	2 / 120	not stated; safety; R0018977:Table 4
A3	events	1 / 120	not stated; randomized; R0018977:Supplement Figure S3
A3	events	4 / 119	not stated; safety; R0018977:Table 4
A4	events	5 / 115	not stated; randomized; R0018977:Supplement Figure S3
A4	events	8 / 114	not stated; safety; R0018977:Table 4

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	29 / 114	not stated; safety; R0018977:Table 4
A2	events	12 / 120	not stated; safety; R0018977:Table 4
A3	events	26 / 119	not stated; safety; R0018977:Table 4
A4	events	6 / 114	not stated; safety; R0018977:Table 4

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	20 / 114	not stated; safety; R0018977:Table 4
A2	events	5 / 120	not stated; safety; R0018977:Table 4
A3	events	11 / 119	not stated; safety; R0018977:Table 4
A4	events	1 / 114	not stated; safety; R0018977:Table 4

Diarrhea (8 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	30 / 114	not stated; safety; R0018977:Table 4
A1	events	1 / 114	not stated; safety; registry:adverse_events
A2	events	15 / 120	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; registry:adverse_events
A3	events	26 / 119	not stated; safety; R0018977:Table 4
A3	events	1 / 119	not stated; safety; registry:adverse_events
A4	events	10 / 114	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	18 / 114	not stated; safety; R0018977:Table 4
A2	events	3 / 120	not stated; safety; R0018977:Table 4
A3	events	18 / 119	not stated; safety; R0018977:Table 4
A4	events	5 / 114	not stated; safety; R0018977:Table 4

Gallbladder and biliary disease (16 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	0 / 114	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 114	not stated; safety; gallbladder polyp; registry:adverse_events
A1	events	0 / 114	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	1 / 120	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	0 / 120	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	1 / 120	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 120	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 119	not stated; safety; gallbladder polyp; registry:adverse_events
A3	events	0 / 119	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	2 / 119	not stated; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 119	not stated; safety; gallbladder polyp; registry:adverse_events
A4	events	0 / 114	not stated; safety; gallbladder polyp; registry:adverse_events
A4	events	0 / 114	not stated; safety; gallbladder polyp; registry:adverse_events
A4	events	0 / 114	not stated; safety; cholelithiasis; registry:adverse_events
A4	events	1 / 114	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (12 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A1	events	0 / 114	not stated; safety; registry:adverse_events
A1	events	0 / 114	not stated; safety; registry:adverse_events
A2	events	0 / 120	not stated; safety; registry:adverse_events
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; registry:adverse_events
A3	events	2 / 119	not stated; safety; R0018977:Table 4
A3	events	1 / 119	not stated; safety; registry:adverse_events
A3	events	1 / 119	not stated; safety; registry:adverse_events
A4	events	0 / 114	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; registry:adverse_events
A4	events	0 / 114	not stated; safety; registry:adverse_events

Medullary thyroid carcinoma (4 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; R0018977:Table 4

Thyroid cancer (any) (4 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; R0018977:Table 4

Suicidal ideation or behavior (4 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	2 / 114	not stated; safety; suicide attempt; registry:adverse_events
A2	events	0 / 120	not stated; safety; suicide attempt; registry:adverse_events
A3	events	0 / 119	not stated; safety; suicide attempt; registry:adverse_events
A4	events	0 / 114	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (4 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 114	not stated; safety; R0018977:Table 4
A2	events	0 / 120	not stated; safety; R0018977:Table 4
A3	events	0 / 119	not stated; safety; R0018977:Table 4
A4	events	0 / 114	not stated; safety; R0018977:Table 4

Apnea hypopnea index change (78 lines; O70)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-27.4 events per hour		-31.6 to -23.2		hypothetical; modified itt; R0018977:Results
52	A1 vs A2	md	-22.5 events per hour		-28.7 to -16.4		hypothetical; modified itt; R0018977:Results
52	A1	change	-12.1 events per hour	2.11			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A1 vs A2	md	-23.9 events per hour		-31.6 to -16.3		hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A1	change	-30.6 events per hour	2.59			hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A1 vs A2	md	-18.8 events per hour		-29.9 to -7.6		hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A1	change	-25.3 events per hour		-29.3 to -21.2	114	treatment policy; modified itt; R0018977:Table 2
52	A1	percent change	-50.7 percent		-62.3 to -39.1	114	treatment policy; modified itt; R0018977:Table 2
52	A1 vs A2	md	-20.0 events per hour		-25.8 to -14.2		treatment policy; modified itt; R0018977:Table 2
52	A1 vs A2	md	-47.7 percent		-65.8 to -29.6		treatment policy; modified itt; R0018977:Table 2
52	A1 vs A2	md	-11.3 events per hour		-17.4 to -5.2		hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A1	change	-28.3 events per hour	3.88			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A1	change	-19.8 events per hour	3.86			hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A1 vs A2	md	-26.4 events per hour		-39.3 to -13.5		hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A1	change	-27.9 events per hour	4.31			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A1 vs A2	md	-23.5 events per hour		-32.6 to -14.3		hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A1	change	-29.2 events per hour	3.11			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A1 vs A2	md	-19.0 events per hour		-29.2 to -8.8		hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A1	change	-27.8 events per hour	3.08			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A1 vs A2	md	-23.7 events per hour		-32.3 to -15.2		hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A1 vs A2	md	-30.5 events per hour		-41.8 to -19.3		hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A1	change	-25.2 events per hour	3.49			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A1 vs A2	md	-26.2 events per hour		-40.8 to -11.7		hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A1	change	-43.3 events per hour	4.74			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A1	change	-27.9 events per hour	3.01			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A1 vs A2	md	-22.9 events per hour		-32.2 to -13.7		hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A2	change	-4.8 events per hour		-9.3 to -0.3		hypothetical; modified itt; R0018977:Results
52	A2	change	-5.3 events per hour		-9.4 to -1.1	120	treatment policy; modified itt; R0018977:Table 2
52	A2	percent change	-3.0 percent		-16.9 to 10.9	120	treatment policy; modified itt; R0018977:Table 2
52	A2	change	-4.0 events per hour	2.94			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S8
52	A2	change	-4.9 events per hour	3.54			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S8
52	A2	change	-0.8 events per hour	2.23			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S12
52	A2	change	2.2 events per hour	4.04			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S12
52	A2	change	-17.1 events per hour	5.36			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S12
52	A2	change	-6.2 events per hour	3.67			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S14
52	A2	change	-5.7 events per hour	3.35			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S14
52	A2	change	-1.4 events per hour	4.77			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S14
52	A2	change	-1.1 events per hour	3.90			hypothetical; modified itt; sex:female; R0005976:Supplement Table S10
52	A2	change	-6.6 events per hour	2.85			hypothetical; modified itt; sex:male; R0005976:Supplement Table S10
52	A3	change	-30.9 events per hour	2.52			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A3 vs A4	md	-22.5 events per hour		-30.9 to -14.1		hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A3 vs A4	md	-23.8 events per hour		-29.6 to -17.9		treatment policy; modified itt; R0018977:Table 2
52	A3	percent change	-58.7 percent		-69.1 to -48.4	120	treatment policy; modified itt; R0018977:Table 2
52	A3	change	-32.6 events per hour	2.48			hypothetical; modified itt; sex:male; R0005976:Supplement Table S11
52	A3	change	-26.0 events per hour	3.47			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A3 vs A4	md	-21.8 events per hour		-32.4 to -11.2		hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A3	change	-29.3 events per hour		-33.2 to -25.4	120	treatment policy; modified itt; R0018977:Table 2
52	A3 vs A4	md	-25.1 events per hour				hypothetical; modified itt; sex:male; R0005976:Supplement Table S11
52	A3	change	-24.8 events per hour	3.24			hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A3 vs A4	md	-23.1 events per hour		-32.6 to -13.5		hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A3	change	-12.6 events per hour	2.84			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A3 vs A4	md	-17.1 events per hour		-25.5 to -8.7		hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A3 vs A4	md	-28.6 events per hour		-38.6 to -18.5		hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A3	change	-34.1 events per hour	3.14			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A3 vs A4	md	-21.9 events per hour		-29.3 to -14.5		hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A3 vs A4	md	-24.4 events per hour		-30.3 to -18.6		hypothetical; modified itt; R0018977:Results
52	A3	change	-52.2 events per hour	6.15			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A3 vs A4	md	-34.0 events per hour		-50.1 to -17.8		hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A3	change	-27.7 events per hour	2.58			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A3	change	-30.4 events per hour		-34.3 to -26.5		hypothetical; modified itt; R0018977:Results
52	A3	change	-30.3 events per hour	3.35			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15
52	A3 vs A4	md	-23.0 events per hour		-32.9 to -13.0		hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15
52	A3 vs A4	md	-56.2 percent		-73.7 to -38.7		treatment policy; modified itt; R0018977:Table 2
52	A3	change	-34.4 events per hour	3.49			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A3 vs A4	md	-27.8 events per hour		-38.5 to -17.1		hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A4	change	-8.4 events per hour	3.38			hypothetical; modified itt; ahi:30_to_less_than_70; R0005976:Supplement Table S13
52	A4	change	-5.8 events per hour	2.68			hypothetical; modified itt; age:50_or_older; R0005976:Supplement Table S9
52	A4	change	-5.5 events per hour		-9.9 to -1.2	115	treatment policy; modified itt; R0018977:Table 2
52	A4	change	-6.0 events per hour		-10.3 to -1.6		hypothetical; modified itt; R0018977:Results
52	A4	change	-7.5 events per hour	2.78			hypothetical; modified itt; sex:male; R0005976:Supplement Table S11
52	A4	change	-1.8 events per hour	3.49			hypothetical; modified itt; sex:female; R0005976:Supplement Table S11
52	A4	change	-18.2 events per hour	5.09			hypothetical; modified itt; ahi:70_or_more; R0005976:Supplement Table S13
52	A4	change	4.5 events per hour	3.07			hypothetical; modified itt; ahi:15_to_less_than_30; R0005976:Supplement Table S13
52	A4	percent change	-2.5 percent		-16.2 to 11.2	115	treatment policy; modified itt; R0018977:Table 2
52	A4	change	-6.6 events per hour	4.04			hypothetical; modified itt; bmi:35_to_less_than_40; R0005976:Supplement Table S15
52	A4	change	-4.2 events per hour	3.91			hypothetical; modified itt; bmi:40_or_more; R0005976:Supplement Table S15
52	A4	change	-5.6 events per hour	3.86			hypothetical; modified itt; age:less_than_50; R0005976:Supplement Table S9
52	A4	change	-7.4 events per hour	3.54			hypothetical; modified itt; bmi:30_to_less_than_35; R0005976:Supplement Table S15