parallel randomized trial

AWARD-11

A Randomized, Double-Blind, Parallel Arm Study of the Efficacy and Safety of Investigational Dulaglutide Doses When Added to Metformin in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT03495102S000046

Design

Randomized: 1,842
Start year: 2018
Treatment: 52 weeks, follow-up 56 weeks
Countries: Argentina, Austria, Canada, Greece, Hungary, Israel, Italy, Mexico, Poland, Romania, Russia, Slovakia, Spain, Taiwan, United States (203 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 18 or older; HbA1c 7.5 to 11.0%; BMI 25 or more; metformin 1500 mg/day or more; GLP-1 RA and insulin naive

Conduct and analysis

Blinding: double blind
Sequence generation: not reported
Allocation concealment: not reported
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	Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg	metformin 1500 mg daily or more; lifestyle: not reported	612	612	533
A2	Dulaglutide 3.0 mg subcutaneous once weekly Dulaglutide 3.0 mg	metformin 1500 mg daily or more; lifestyle: not reported	616	616	523
A3	Dulaglutide 4.5 mg subcutaneous once weekly Dulaglutide 4.5 mg	metformin 1500 mg daily or more; lifestyle: not reported	614	614	520

Baseline characteristics

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

Characteristic	Statistic	Dulaglutide 1.5 mg subcutaneous once weekly A1	Dulaglutide 3.0 mg subcutaneous once weekly A2	Dulaglutide 4.5 mg subcutaneous once weekly A3
age: 65 or older	n	156	150	132
age: 65 or older	percent	25.5	24.4	21.5
age: 75 or older	n	20	14	21
age: 75 or older	percent	3.3	2.3	3.4
age	mean (years)	57.8	56.9	56.6
age	sd (years)	9.7	10.2	10.2
asian	n	13	18	14
asian	percent	2.1	2.9	2.3
black	n	28	31	23
black	percent	4.6	5.0	3.7
bmi	mean (kg/m2)	34.4	34.3	34.0
bmi	sd (kg/m2)	6.4	6.2	6.2
diabetes duration	mean (years)	7.6	7.6	7.7
diabetes duration	sd (years)	5.8	5.5	5.8
egfr: 30 to less than 60	n	33	25	33
egfr: 30 to less than 60	percent	5.4	4.1	5.4
egfr: 60 to less than 90	n	171	198	184
egfr: 60 to less than 90	percent	27.9	32.1	30.0
egfr: 90 or more	n	408	393	397
egfr: 90 or more	percent	66.7	63.8	64.7
egfr	mean (mL/min/1.73 m2)	93.4	93.3	93.7
egfr	sd (mL/min/1.73 m2)	18.2	17.8	18.3
established cvd	n	99	93	84
established cvd	percent	16.2	15.1	13.7
female	n	314	288	296
female	percent	51.3	46.8	48.2
hba1c	mean (percent)	8.6	8.6	8.6
hba1c	sd (percent)	0.9	1.0	0.9
hispanic	n	214	214	213
other race american indian alaska native	n	30	26	32
other race american indian alaska native	percent	4.9	4.2	5.2
other race multiple	n	11	19	12
other race multiple	percent	1.8	3.1	2.0
other race native hawaiian pacific islander	n	1	1	3
other race native hawaiian pacific islander	percent	0.2	0.2	0.5
sbp	mean (mmHg)	132.1	131.1	132.1
sbp	sd (mmHg)	14.2	14.1	14.0
weight	mean (kg)	95.5	96.3	95.4
weight	sd (kg)	20.2	20.1	20.6
white	n	529	521	530
white	percent	86.4	84.6	86.3

Analyses this trial contributes to

Results

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

HbA1c change (55 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
36	A1	change	-1.53 percent			591	hypothetical; modified itt; R0022783:Figure 2
36	A1	change	-1.6 percent			466	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A1	change	-1.4 percent				hypothetical; modified itt; hba1c:8_to_less_than_9; R0022091:Results
36	A1	change	-1.54 percent			612	treatment policy; modified itt; R0022783:Figure 2A
36	A1	change	-2.1 percent				hypothetical; modified itt; hba1c:9_to_less_than_10; R0022091:Results
36	A1	change	-1.59 percent			389	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A1	change	-1.4 percent			57	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A1	change	-2.2 percent				hypothetical; modified itt; hba1c:10_or_more; R0022091:Results
36	A1	change	-1.0 percent				hypothetical; modified itt; hba1c:less_than_8; R0022091:Results
36	A1	change	-1.53 percent	0.04		523	hypothetical; modified itt; registry:outcomes
36	A1	change	-1.33 percent			134	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A2	change	-2.5 percent				hypothetical; modified itt; hba1c:10_or_more; R0022091:Results
36	A2 vs A1	md	-0.17 percent		-0.29 to -0.06		hypothetical; modified itt; R0022783:Results
36	A2	change	-2.2 percent				hypothetical; modified itt; hba1c:9_to_less_than_10; R0022091:Results
36	A2	change	-1.6 percent			46	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A2	change	-1.74 percent			391	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A2	change	-1.64 percent			616	treatment policy; modified itt; R0022783:Figure 2A
36	A2	change	-1.7 percent			475	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A2 vs A1	md	-0.10 percent		-0.23 to 0.02		treatment policy; modified itt; R0022783:Results
36	A2	change	-1.2 percent				hypothetical; modified itt; hba1c:less_than_8; R0022091:Results
36	A2	change	-1.58 percent			130	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A2	change	-1.6 percent				hypothetical; modified itt; hba1c:8_to_less_than_9; R0022091:Results
36	A2	change	-1.71 percent			595	hypothetical; modified itt; R0022783:Figure 2
36	A2	change	-1.71 percent	0.04		521	hypothetical; modified itt; registry:outcomes
36	A3	change	-1.6 percent			46	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A3	change	-1.87 percent	0.04		526	hypothetical; modified itt; registry:outcomes
36	A3	change	-1.2 percent				hypothetical; modified itt; hba1c:less_than_8; R0022091:Results
36	A3 vs A1	md	-0.34 percent		-0.45 to -0.22		hypothetical; modified itt; R0022783:Results
36	A3	change	-1.77 percent			614	treatment policy; modified itt; R0022783:Figure 2A
36	A3 vs A1	md	-0.24 percent		-0.36 to -0.11		treatment policy; modified itt; R0022783:Results
36	A3	change	-1.87 percent			594	hypothetical; modified itt; R0022783:Figure 2
36	A3	change	-1.65 percent			113	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A3	change	-2.3 percent				hypothetical; modified itt; hba1c:9_to_less_than_10; R0022091:Results
36	A3	change	-1.94 percent			413	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A3	change	-1.9 percent			480	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A3	change	-3.2 percent				hypothetical; modified itt; hba1c:10_or_more; R0022091:Results
36	A3	change	-1.8 percent				hypothetical; modified itt; hba1c:8_to_less_than_9; R0022091:Results
52	A1	change	-1.55 percent			612	treatment policy; modified itt; R0022783:Figure 2A
52	A1	change	-1.52 percent			591	hypothetical; modified itt; R0022783:Figure 2
52	A2 vs A1	md	-0.19 percent		-0.31 to -0.07		hypothetical; modified itt; R0022783:Figure 2
52	A2	change	-1.71 percent			595	hypothetical; modified itt; R0022783:Figure 2
52	A2 vs A1	md	-0.22 percent				hypothetical; modified itt; hba1c:9_to_less_than_10; R0022091:Supplementary Figure 2
52	A2 vs A1	md	-0.15 percent				hypothetical; modified itt; hba1c:8_to_less_than_9; R0022091:Supplementary Figure 2
52	A2 vs A1	md	-0.06 percent		-0.20 to 0.08		treatment policy; modified itt; R0022783:Figure 2A
52	A2 vs A1	md	-0.19 percent				hypothetical; modified itt; hba1c:less_than_8; R0022091:Supplementary Figure 2
52	A2	change	-1.61 percent			616	treatment policy; modified itt; R0022783:Figure 2A
52	A2 vs A1	md	-0.39 percent				hypothetical; modified itt; hba1c:10_or_more; R0022091:Supplementary Figure 2
52	A3	change	-1.83 percent			594	hypothetical; modified itt; R0022783:Figure 2
52	A3 vs A1	md	-0.31 percent		-0.43 to -0.19		hypothetical; modified itt; R0022783:Figure 2
52	A3	change	-1.72 percent			614	treatment policy; modified itt; R0022783:Figure 2A
52	A3 vs A1	md	-0.17 percent		-0.31 to -0.03		treatment policy; modified itt; R0022783:Figure 2A
52	A3 vs A1	md	-0.87 percent				hypothetical; modified itt; hba1c:10_or_more; R0022091:Figure 1C
52	A3 vs A1	md	-0.29 percent				hypothetical; modified itt; hba1c:8_to_less_than_9; R0022091:Figure 1C
52	A3 vs A1	md	-0.36 percent				hypothetical; modified itt; hba1c:9_to_less_than_10; R0022091:Figure 1C
52	A3 vs A1	md	-0.10 percent				hypothetical; modified itt; hba1c:less_than_8; R0022091:Figure 1C

Body weight change in kilograms (diabetes) (94 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
36	A1	change	-3.1 kg	0.19		601	hypothetical; modified itt; R0022086:Results
36	A1	change	-3.1 kg			601	hypothetical; modified itt; R0022783:Figure 2
36	A1	change	-3.9 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3B
36	A1	change	-3.1 kg			134	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A1	change	-2.8 kg			57	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A1	change	-3.1 kg			388	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A1	change	-3.3 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3D
36	A1	change	-2.9 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3D
36	A1	change	-3.0 kg			612	treatment policy; modified itt; R0022783:Figure 2F
36	A1	change	-3.2 kg			465	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A1	change	-2.7 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
36	A1	change	-2.3 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3B
36	A1	change	-1.9 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
36	A1	change	-4.9 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
36	A1	change	-3.8 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
36	A2	change	-4.2 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
36	A2	change	-4.0 kg	0.19		604	hypothetical; modified itt; R0022086:Results
36	A2	change	-4.0 kg			604	hypothetical; modified itt; R0022783:Figure 2
36	A2 vs A1	md	-0.9 kg		-1.4 to -0.4		hypothetical; modified itt; R0022783:Results
36	A2	change	-3.8 kg			616	treatment policy; modified itt; R0022783:Figure 2F
36	A2 vs A1	md	-0.9 kg		-1.4 to -0.4		treatment policy; modified itt; R0022783:Figure 2F
36	A2	change	-4.3 kg			130	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A2	change	-4.7 kg			46	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A2	change	-3.9 kg			390	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A2	change	-3.9 kg			474	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A2	change	-3.7 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
36	A2	change	-4.6 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3B
36	A2 vs A1	md	-0.7 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3B
36	A2	change	-5.6 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
36	A2	change	-3.2 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
36	A2	change	-3.4 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3B
36	A2 vs A1	md	-1.1 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3B
36	A2	change	-3.3 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3D
36	A2 vs A1	md	-0.4 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3D
36	A2	change	-4.7 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3D
36	A2 vs A1	md	-1.3 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3D
36	A3	change	-4.8 kg			46	hypothetical; modified itt; age:70_or_older; R0021968:Figure 2
36	A3 vs A1	md	-1.0 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3D
36	A3	change	-4.7 kg			480	hypothetical; modified itt; age:less_than_70; R0021968:Figure 2
36	A3	change	-4.7 kg			604	hypothetical; modified itt; R0022783:Figure 2
36	A3 vs A1	md	-2.2 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3D
36	A3	change	-5.5 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3D
36	A3	change	-4.8 kg			413	hypothetical; modified itt; age:less_than_65; R0021968:Figure 1
36	A3	change	-3.9 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3D
36	A3	change	-5.6 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3B
36	A3 vs A1	md	-1.7 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3B
36	A3	change	-4.5 kg			113	hypothetical; modified itt; age:65_or_older; R0021968:Figure 1
36	A3	change	-5.3 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
36	A3	change	-6.0 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
36	A3	change	-4.4 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
36	A3 vs A1	md	-1.6 kg		-2.2 to -1.1		treatment policy; modified itt; R0022783:Results
36	A3	change	-3.8 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
36	A3	change	-4.6 kg			614	treatment policy; modified itt; R0022783:Figure 2F
36	A3	change	-3.9 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3B
36	A3 vs A1	md	-1.6 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3B
36	A3 vs A1	md	-1.6 kg		-2.1 to -1.1		hypothetical; modified itt; R0022783:Results
36	A3	change	-4.7 kg	0.19		604	hypothetical; modified itt; R0022086:Results
52	A1	change	-2.0 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
52	A1	change	-3.0 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3C
52	A1	change	-3.3 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
52	A1	change	-4.3 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3A
52	A1	change	-3.9 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3C
52	A1	change	-3.5 kg	0.21		601	hypothetical; modified itt; R0022086:Table 1
52	A1	change	-3.5 kg			601	hypothetical; modified itt; R0022783:Figure 2
52	A1	change	-5.3 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
52	A1	change	-3.4 kg			612	treatment policy; modified itt; R0022783:Figure 2F
52	A1	change	-4.1 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
52	A1	change	-2.5 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3A
52	A2	change	-3.3 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3A
52	A2 vs A1	md	-0.8 kg		-1.4 to -0.2		hypothetical; modified itt; R0022783:Figure 2
52	A2	change	-4.7 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
52	A2 vs A1	md	-0.6 kg		-1.2 to 0.0		treatment policy; modified itt; R0022783:Figure 2F
52	A2	change	-5.1 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3C
52	A2	change	-3.5 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3C
52	A2	change	-6.2 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
52	A2	change	-3.9 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
52	A2	change	-4.0 kg			616	treatment policy; modified itt; R0022783:Figure 2F
52	A2	change	-4.3 kg	0.21		604	hypothetical; modified itt; R0022086:Table 1
52	A2	change	-3.2 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
52	A2	change	-5.2 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3A
52	A2	change	-4.3 kg			604	hypothetical; modified itt; R0022783:Figure 2
52	A3 vs A1	md	-1.5 kg		-2.2 to -0.9		treatment policy; modified itt; R0022783:Figure 2F
52	A3	change	-4.7 kg				hypothetical; modified itt; bmi:30_to_less_than_35; R0022086:Figure 2A
52	A3	change	-5.7 kg				hypothetical; modified itt; bmi:33.2_or_more; R0022086:Supplementary Figure S3A
52	A3	change	-5.5 kg				hypothetical; modified itt; bmi:35_to_less_than_40; R0022086:Figure 2A
52	A3	change	-6.3 kg				hypothetical; modified itt; bmi:40_or_more; R0022086:Figure 2A
52	A3	change	-4.3 kg				hypothetical; modified itt; bmi:less_than_30; R0022086:Figure 2A
52	A3	change	-4.4 kg				hypothetical; modified itt; bmi:less_than_33.2; R0022086:Supplementary Figure S3A
52	A3	change	-4.1 kg				hypothetical; modified itt; hba1c:8.5_or_more; R0022086:Supplementary Figure S3C
52	A3	change	-6.0 kg				hypothetical; modified itt; hba1c:less_than_8.5; R0022086:Supplementary Figure S3C
52	A3	change	-4.9 kg			614	treatment policy; modified itt; R0022783:Figure 2F
52	A3 vs A1	md	-1.6 kg		-2.2 to -1.0		hypothetical; modified itt; R0022783:Figure 2
52	A3	change	-5.0 kg			604	hypothetical; modified itt; R0022783:Figure 2
52	A3	change	-5.0 kg	0.21		604	hypothetical; modified itt; R0022086:Table 1

HbA1c below 7 percent (20 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
36	A1	responders	57.0		591	hypothetical; modified itt; R0022783:Figure 2
36	A1	responders	49.7		612	treatment policy; modified itt; R0022783:Figure 2D
36	A2 vs A1	or	1.49	1.12 to 1.98		hypothetical; modified itt; R0022783:Figure 2
36	A2	responders	55.8		616	treatment policy; modified itt; R0022783:Figure 2D
36	A2	responders	64.7		595	hypothetical; modified itt; R0022783:Figure 2
36	A2 vs A1	or	1.32	1.03 to 1.68		treatment policy; modified itt; R0022783:Figure 2D
36	A3	responders	71.5		594	hypothetical; modified itt; R0022783:Figure 2
36	A3	responders	62.2		614	treatment policy; modified itt; R0022783:Figure 2D
36	A3 vs A1	or	1.78	1.39 to 2.27		treatment policy; modified itt; R0022783:Figure 2D
36	A3 vs A1	or	2.23	1.65 to 3.01		hypothetical; modified itt; R0022783:Figure 2
52	A1	responders	49.3		612	treatment policy; modified itt; R0022783:Figure 2D
52	A1	responders	58.6		591	hypothetical; modified itt; R0022783:Figure 2
52	A2 vs A1	or	1.23	0.96 to 1.56		treatment policy; modified itt; R0022783:Figure 2D
52	A2	responders	65.4		595	hypothetical; modified itt; R0022783:Figure 2
52	A2	responders	54.1		616	treatment policy; modified itt; R0022783:Figure 2D
52	A2 vs A1	or	1.41	1.06 to 1.88		hypothetical; modified itt; R0022783:Figure 2
52	A3	responders	71.7		594	hypothetical; modified itt; R0022783:Figure 2
52	A3	responders	59.4		614	treatment policy; modified itt; R0022783:Figure 2D
52	A3 vs A1	or	1.58	1.24 to 2.01		treatment policy; modified itt; R0022783:Figure 2D
52	A3 vs A1	or	2.00	1.47 to 2.72		hypothetical; modified itt; R0022783:Figure 2

Level 2 or 3 hypoglycemia (participants) (9 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	8 / 612	not stated; safety; R0022783:Table 2
A1	events	1 / 612	not stated; safety; R0022783:Table 2
A1	events	1 / 612	not stated; safety; registry:adverse_events
A2	events	0 / 616	not stated; safety; registry:adverse_events
A2	events	0 / 616	not stated; safety; R0022783:Table 2
A2	events	2 / 616	not stated; safety; R0022783:Table 2
A3	events	1 / 614	not stated; safety; registry:adverse_events
A3	events	7 / 614	not stated; safety; R0022783:Table 2
A3	events	1 / 614	not stated; safety; R0022783:Table 2

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Estimate	SE or SD	Events / N	Detail
A1	rate	0.017		612	not stated; safety; R0022783:Results
A1	rate	0.02	0.01	612	hypothetical; modified itt; registry:outcomes
A2	rate	0.00	0.00	616	hypothetical; modified itt; registry:outcomes
A2	rate	0.003		616	not stated; safety; R0022783:Results
A3	rate	0.02		614	not stated; safety; R0022783:Results
A3	rate	0.02	0.01	614	hypothetical; modified itt; registry:outcomes

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Detail
52	A1	change	-3.2 mmHg	0.5	hypothetical; safety; R0021508:Table 2
52	A2	change	-3.6 mmHg	0.5	hypothetical; safety; R0021508:Table 2
52	A3	change	-4.1 mmHg	0.5	hypothetical; safety; R0021508:Table 2

Percent body weight change (6 lines; O10)

Week	Arm	Statistic	Estimate	Detail
36	A1	percent change	-3.3 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4
36	A2	percent change	-4.2 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4
36	A3	percent change	-5.0 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4
52	A1	percent change	-3.6 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4
52	A2	percent change	-4.4 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4
52	A3	percent change	-5.4 percent	hypothetical; modified itt; R0022086:Supplementary Figure S4

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
36	A1	responders	31		601	hypothetical; modified itt; R0022086:Figure 1B
36	A2	responders	40		604	hypothetical; modified itt; R0022086:Figure 1B
36	A2 vs A1	or	1.5	1.2 to 1.9		hypothetical; modified itt; R0022086:Figure 1B
36	A3	responders	49		604	hypothetical; modified itt; R0022086:Figure 1B
36	A3 vs A1	or	2.2	1.7 to 2.8		hypothetical; modified itt; R0022086:Figure 1B
52	A1	responders	34		601	hypothetical; modified itt; R0022086:Figure 1B
52	A2	responders	44		604	hypothetical; modified itt; R0022086:Figure 1B
52	A2 vs A1	or	1.6	1.2 to 2.0		hypothetical; modified itt; R0022086:Figure 1B
52	A3	responders	51		604	hypothetical; modified itt; R0022086:Figure 1B
52	A3 vs A1	or	2.1	1.6 to 2.7		hypothetical; modified itt; R0022086:Figure 1B

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
36	A1	responders	6		601	hypothetical; modified itt; R0022086:Figure 1B
36	A2	responders	12		604	hypothetical; modified itt; R0022086:Figure 1B
36	A2 vs A1	or	2.1	1.4 to 3.3		hypothetical; modified itt; R0022086:Figure 1B
36	A3	responders	14		604	hypothetical; modified itt; R0022086:Figure 1B
36	A3 vs A1	or	2.4	1.5 to 3.7		hypothetical; modified itt; R0022086:Figure 1B
52	A1	responders	10		601	hypothetical; modified itt; R0022086:Figure 1B
52	A2	responders	13		604	hypothetical; modified itt; R0022086:Figure 1B
52	A2 vs A1	or	1.3	0.9 to 1.9		hypothetical; modified itt; R0022086:Figure 1B
52	A3	responders	17		604	hypothetical; modified itt; R0022086:Figure 1B
52	A3 vs A1	or	1.8	1.2 to 2.6		hypothetical; modified itt; R0022086:Figure 1B

Acute kidney injury (6 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	6 / 612	not stated; safety; R0022783:Table 2
A1	events	1 / 612	not stated; safety; registry:adverse_events
A2	events	1 / 616	not stated; safety; registry:adverse_events
A2	events	6 / 616	not stated; safety; R0022783:Table 2
A3	events	0 / 614	not stated; safety; registry:adverse_events
A3	events	5 / 614	not stated; safety; R0022783:Table 2

All cause mortality (3 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	3 / 612	not stated; safety; R0022783:Table 2
A2	events	4 / 616	not stated; safety; R0022783:Table 2
A3	events	4 / 614	not stated; safety; R0022783:Table 2

Hospitalization for heart failure (9 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 612	not stated; safety; Cardiac failure congestive; registry:adverse_events
A1	events	1 / 612	not stated; safety; Cardiac failure; registry:adverse_events
A1	events	0 / 612	not stated; safety; Left ventricular failure; registry:adverse_events
A2	events	0 / 616	not stated; safety; Cardiac failure congestive; registry:adverse_events
A2	events	0 / 616	not stated; safety; Cardiac failure; registry:adverse_events
A2	events	0 / 616	not stated; safety; Left ventricular failure; registry:adverse_events
A3	events	1 / 614	not stated; safety; Cardiac failure congestive; registry:adverse_events
A3	events	1 / 614	not stated; safety; Cardiac failure; registry:adverse_events
A3	events	1 / 614	not stated; safety; Left ventricular failure; registry:adverse_events

Physical functioning (any instrument) (6 lines; O24B)

Week	Arm	Statistic	Estimate	Detail
36	A1	change	2.1 points	hypothetical; modified itt; R0022086:Supplementary Table S3
36	A2	change	3.7 points	hypothetical; modified itt; R0022086:Supplementary Table S3
36	A3	change	4.4 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A1	change	2.2 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A2	change	4.1 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A3	change	4.2 points	hypothetical; modified itt; R0022086:Supplementary Table S3

Health related quality of life total score (any instrument) (6 lines; O24C)

Week	Arm	Statistic	Estimate	Detail
36	A1	change	0.02 points	hypothetical; modified itt; R0022086:Supplementary Table S3
36	A2	change	0.03 points	hypothetical; modified itt; R0022086:Supplementary Table S3
36	A3	change	0.02 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A1	change	0.01 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A2	change	0.03 points	hypothetical; modified itt; R0022086:Supplementary Table S3
52	A3	change	0.03 points	hypothetical; modified itt; R0022086:Supplementary Table S3

Serious adverse events (6 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	51 / 612	not stated; safety; R0022783:Table 2
A1	events	53 / 612	not stated; safety; registry:adverse_events
A2	events	45 / 616	not stated; safety; registry:adverse_events
A2	events	42 / 616	not stated; safety; R0022783:Table 2
A3	events	38 / 614	not stated; safety; registry:adverse_events
A3	events	38 / 614	not stated; safety; R0022783:Table 2

Discontinuation due to adverse events (18 lines; O26)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		5 / 612	not stated; randomized; registry:flow
A1	events		28 / 612	not stated; randomized; R0022783:Figure 1
A1	events	4.2	612	not stated; randomized; R0026303:Abstract
A1	events		6 / 612	not stated; randomized; R0022783:Figure 1
A1	events		8 / 612	not stated; randomized; R0022783:Figure 1
A1	events		37 / 612	not stated; safety; R0022783:Table 2
A2	events		43 / 616	not stated; safety; R0022783:Table 2
A2	events		7 / 616	not stated; randomized; registry:flow
A2	events		11 / 616	not stated; randomized; R0022783:Figure 1
A2	events		36 / 616	not stated; randomized; R0022783:Figure 1
A2	events	5.5	616	not stated; randomized; R0026303:Abstract
A2	events		8 / 616	not stated; randomized; R0022783:Figure 1
A3	events		10 / 614	not stated; randomized; registry:flow
A3	events		32 / 614	not stated; randomized; R0022783:Figure 1
A3	events	5.0	614	not stated; randomized; R0026303:Abstract
A3	events		11 / 614	not stated; randomized; R0022783:Figure 1
A3	events		52 / 614	not stated; safety; R0022783:Table 2
A3	events		14 / 614	not stated; randomized; R0022783:Figure 1

Nausea (6 lines; O27A)

Arm	Statistic	Estimate	Events / N	Detail
A1	events	13.4	612	not stated; randomized; R0026303:Abstract
A1	events		87 / 612	not stated; safety; R0022783:Table 2
A2	events		99 / 616	not stated; safety; R0022783:Table 2
A2	events	15.6	616	not stated; randomized; R0026303:Abstract
A3	events		106 / 614	not stated; safety; R0022783:Table 2
A3	events	16.4	614	not stated; randomized; R0026303:Abstract

Vomiting (9 lines; O27B)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		40 / 612	not stated; safety; registry:adverse_events
A1	events		39 / 612	not stated; safety; R0022783:Table 2
A1	events	5.6	612	not stated; randomized; R0026303:Abstract
A2	events		56 / 616	not stated; safety; R0022783:Table 2
A2	events	8.3	616	not stated; randomized; R0026303:Abstract
A2	events		57 / 616	not stated; safety; registry:adverse_events
A3	events		64 / 614	not stated; safety; registry:adverse_events
A3	events		62 / 614	not stated; safety; R0022783:Table 2
A3	events	9.3	614	not stated; randomized; R0026303:Abstract

Diarrhea (12 lines; O27C)

Arm	Statistic	Estimate	Events / N	Detail
A1	events		0 / 612	not stated; safety; registry:adverse_events
A1	events		47 / 612	not stated; safety; R0022783:Table 2
A1	events	7.0	612	not stated; randomized; R0026303:Abstract
A1	events		48 / 612	not stated; safety; registry:adverse_events
A2	events		74 / 616	not stated; safety; R0022783:Table 2
A2	events	11.4	616	not stated; randomized; R0026303:Abstract
A2	events		75 / 616	not stated; safety; registry:adverse_events
A2	events		0 / 616	not stated; safety; registry:adverse_events
A3	events		1 / 614	not stated; safety; registry:adverse_events
A3	events	10.7	614	not stated; randomized; R0026303:Abstract
A3	events		70 / 614	not stated; safety; registry:adverse_events
A3	events		71 / 614	not stated; safety; R0022783:Table 2

Constipation (3 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	19 / 612	not stated; safety; R0022086:Supplement Table S5
A2	events	26 / 616	not stated; safety; R0022086:Supplement Table S5
A3	events	24 / 614	not stated; safety; R0022086:Supplement Table S5

Discontinuation due to gastrointestinal adverse events (15 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	9 / 612	not stated; safety; common gi events; R0022783:Table 2
A1	events	1 / 612	not stated; safety; diarrhea; R0022783:Table 2
A1	events	0 / 612	not stated; safety; dyspepsia; R0022783:Table 2
A1	events	8 / 612	not stated; safety; nausea; R0022783:Table 2
A1	events	0 / 612	not stated; safety; vomiting; R0022783:Table 2
A2	events	8 / 616	not stated; safety; nausea; R0022783:Table 2
A2	events	21 / 616	not stated; safety; common gi events; R0022783:Table 2
A2	events	6 / 616	not stated; safety; diarrhea; R0022783:Table 2
A2	events	2 / 616	not stated; safety; dyspepsia; R0022783:Table 2
A2	events	5 / 616	not stated; safety; vomiting; R0022783:Table 2
A3	events	9 / 614	not stated; safety; nausea; R0022783:Table 2
A3	events	24 / 614	not stated; safety; common gi events; R0022783:Table 2
A3	events	6 / 614	not stated; safety; diarrhea; R0022783:Table 2
A3	events	1 / 614	not stated; safety; dyspepsia; R0022783:Table 2
A3	events	8 / 614	not stated; safety; vomiting; R0022783:Table 2

Gallbladder and biliary disease (12 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 612	not stated; safety; Cholecystitis acute; registry:adverse_events
A1	events	9 / 612	not stated; safety; R0022783:Table 2
A1	events	0 / 612	not stated; safety; Cholelithiasis; registry:adverse_events
A1	events	0 / 612	not stated; safety; Cholecystitis infective; registry:adverse_events
A2	events	11 / 616	not stated; safety; R0022783:Table 2
A2	events	2 / 616	not stated; safety; Cholecystitis acute; registry:adverse_events
A2	events	1 / 616	not stated; safety; Cholecystitis infective; registry:adverse_events
A2	events	0 / 616	not stated; safety; Cholelithiasis; registry:adverse_events
A3	events	1 / 614	not stated; safety; Cholelithiasis; registry:adverse_events
A3	events	0 / 614	not stated; safety; Cholecystitis infective; registry:adverse_events
A3	events	2 / 614	not stated; safety; Cholecystitis acute; registry:adverse_events
A3	events	10 / 614	not stated; safety; R0022783:Table 2

Acute pancreatitis (9 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 612	not stated; safety; R0022783:Table 2
A1	events	0 / 612	not stated; safety; registry:adverse_events
A1	events	0 / 612	not stated; safety; obstructive pancreatitis; registry:adverse_events
A2	events	2 / 616	not stated; safety; R0022783:Table 2
A2	events	0 / 616	not stated; safety; registry:adverse_events
A2	events	1 / 616	not stated; safety; obstructive pancreatitis; registry:adverse_events
A3	events	3 / 614	not stated; safety; R0022783:Table 2
A3	events	1 / 614	not stated; safety; registry:adverse_events
A3	events	0 / 614	not stated; safety; obstructive pancreatitis; registry:adverse_events

Medullary thyroid carcinoma (3 lines; O32A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 612	not stated; safety; R0022783:Results
A2	events	0 / 616	not stated; safety; R0022783:Results
A3	events	0 / 614	not stated; safety; R0022783:Results

Thyroid cancer (any) (3 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 612	not stated; safety; Papillary thyroid cancer; registry:adverse_events
A2	events	0 / 616	not stated; safety; Papillary thyroid cancer; registry:adverse_events
A3	events	0 / 614	not stated; safety; Papillary thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (3 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	4 / 612	not stated; safety; diabetic retinopathy; R0022783:Results
A2	events	1 / 616	not stated; safety; diabetic retinopathy; R0022783:Results
A3	events	3 / 614	not stated; safety; diabetic retinopathy; R0022783:Results

Suicidal ideation or behavior (3 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 612	not stated; safety; Suicidal ideation; registry:adverse_events
A2	events	0 / 616	not stated; safety; Suicidal ideation; registry:adverse_events
A3	events	0 / 614	not stated; safety; Suicidal ideation; registry:adverse_events

Intestinal obstruction or ileus (3 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 612	not stated; safety; Small intestinal obstruction; registry:adverse_events
A2	events	0 / 616	not stated; safety; Small intestinal obstruction; registry:adverse_events
A3	events	0 / 614	not stated; safety; Small intestinal obstruction; registry:adverse_events

Pancreatic cancer (6 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	1 / 612	not stated; safety; Adenocarcinoma pancreas; registry:adverse_events
A1	events	0 / 612	not stated; safety; R0022783:Results
A2	events	0 / 616	not stated; safety; R0022783:Results
A2	events	0 / 616	not stated; safety; Adenocarcinoma pancreas; registry:adverse_events
A3	events	0 / 614	not stated; safety; Adenocarcinoma pancreas; registry:adverse_events
A3	events	0 / 614	not stated; safety; R0022783:Results