parallel randomized trial

SUSTAIN

Efficacy and Safety of Semaglutide Once-weekly Versus Sitagliptin Once-daily as add-on to Metformin in Subjects With Type 2 Diabetes. A 30-week Randomised, Double-blind, Double-dummy, Active-controlled, Parallel-group, Multi-centre and Multi-national Trial

Type 2 diabetes (adults)NCT03061214S001311

Design

Randomized: 868
Start year: 2017
Treatment: 30 weeks, follow-up 35 weeks
Countries: Brazil, China, Taiwan, Hong Kong, South Korea, South Africa, Ukraine (65 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: Adults 18 or older, HbA1c 7.0 to 10.5 percent on metformin monotherapy, eGFR 60 or more

Conduct and analysis

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

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 0.5 mg subcutaneous once weekly Semaglutide 0.5 mg	metformin; lifestyle: not reported	288	288	251
A2	Semaglutide 1.0 mg subcutaneous once weekly Semaglutide 1.0 mg	metformin; lifestyle: not reported	290	290	244
A3	Sitagliptin Sitagliptin 100 mg	metformin; lifestyle: not reported	290	290	273

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	Sitagliptin A3	Whole trial ALL
age	mean (years)	53.0	53.0	53.1
age	sd (years)	11.4	10.6	10.4
asian	n	243	251	244
asian	percent	84.4	86.6	84.1
black	n	8	8	9
black	percent	2.8	2.8	3.1
bmi	mean (kg/m2)	28.2	27.9	27.3
bmi	sd (kg/m2)	5.0	5.0	4.7
diabetes duration	mean (years)	6.3	6.7	6.1
diabetes duration	sd (years)	5.4	4.9	5.2
egfr	max (mL/min/1.73 m2)	196	274	222
egfr	median (mL/min/1.73 m2)	109.0	110.0	109.0
egfr	min (mL/min/1.73 m2)	59	61	60
female	n	128	136	105
female	percent	44.4	46.9	36.2
hba1c	mean (percent)	8.1	8.1	8.1
hba1c	sd (percent)	0.9	0.9	0.9
hispanic	n	24	28	30
hispanic	percent	8.3	9.7	10.3
metformin use	n	287	289	290
metformin use	percent	99.7	99.7	100
other race american indian alaska native	n	0	0	0
other race multiple	n	0	0	0
other race native hawaiian pacific islander	n	0	0	0
sbp	mean (mmHg)				128.8
sbp	sd (mmHg)				14.6
waist	mean (cm)				96.1
waist	sd (cm)				12.0
weight	mean (kg)	77.6	76.1	75.5
weight	sd (kg)	16.4	16.3	14.7
white	n	30	28	31
white	percent	10.4	9.7	10.7

Analyses this trial contributes to

Results

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

HbA1c change (49 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-0.47 percent		-0.62 to -0.32		hypothetical; full analysis; R0014802:Supplement Figure S5
30	A1 vs A3	md	-0.59 percent		-0.86 to -0.31		hypothetical; other; region:china_female; R0014802:Supplement Table S13
30	A1 vs A3	md	-0.51 percent		-0.66 to -0.36		hypothetical; full analysis; R0014802:Table 2
30	A1 vs A3	md	-0.51 percent		-0.73 to -0.30		hypothetical; other; region:china_male; R0014802:Supplement Table S13
30	A1	change	-1.5 percent	1.1		288	hypothetical; full analysis; registry:outcomes
30	A1	change	-1.5 percent				hypothetical; other; region:china; R0014802:Supplement Table S9
30	A1 vs A3	md	-0.53 percent		-0.70 to -0.36		hypothetical; other; region:china; R0014802:Supplement Table S9
30	A1 vs A3	md	-0.55 percent		-0.74 to -0.35		hypothetical; other; sex:male; R0014802:Supplement Table S12
30	A1 vs A3	md	-0.50 percent		-0.74 to -0.27		hypothetical; other; sex:female; R0014802:Supplement Table S12
30	A1	change	-1.6 percent				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A1 vs A3	md	-0.47 percent		-0.74 to -0.19		hypothetical; other; region:other_countries; R0014802:Supplement Table S10
30	A1 vs A3	md	-0.04 percent		-0.77 to 0.84		hypothetical; other; region:ukraine; R0014802:Supplement Table S11
30	A1 vs A3	md	-0.19 percent		-0.84 to -0.47		hypothetical; other; region:south_africa; R0014802:Supplement Table S11
30	A1 vs A3	md	-0.66 percent		-1.08 to -0.24		hypothetical; other; region:republic_of_korea; R0014802:Supplement Table S11
30	A1	change	-1.5 percent	1.1		288	treatment policy; full analysis; registry:outcomes
30	A1 vs A3	md	-0.51 percent		-0.66 to -0.37		treatment policy; full analysis; R0014802:Supplement Figure S5
30	A1 vs A3	md	-0.49 percent		-0.66 to -0.33		treatment policy; full analysis; R0014802:Supplement Figure S5
30	A1	change	-1.4 percent			288	hypothetical; full analysis; R0014802:Table 2
30	A1 vs A3	md	-0.51 percent		-0.65 to -0.36		hypothetical; completers; R0014802:Supplement Figure S5
30	A1 vs A3	md	-0.46 percent		-0.61 to -0.32		hypothetical; full analysis; R0014802:Supplement Figure S5
30	A1 vs A3	md	-0.64 percent		-1.03 to -0.26		hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A1 vs A3	md	-0.57 percent		-1.06 to -0.07		hypothetical; other; region:brazil; R0014802:Supplement Table S11
30	A2 vs A3	md	-0.77 percent		-0.92 to -0.62		hypothetical; full analysis; R0014802:Supplement Figure S5
30	A2 vs A3	md	-0.79 percent		-0.93 to -0.64		hypothetical; completers; R0014802:Supplement Figure S5
30	A2 vs A3	md	-0.75 percent		-0.90 to -0.60		hypothetical; full analysis; R0014802:Supplement Figure S5
30	A2	change	-1.7 percent	1.0		290	treatment policy; full analysis; registry:outcomes
30	A2 vs A3	md	-0.76 percent		-0.90 to -0.61		treatment policy; full analysis; R0014802:Supplement Figure S5
30	A2 vs A3	md	-0.66 percent		-0.82 to -0.49		treatment policy; full analysis; R0014802:Supplement Figure S5
30	A2 vs A3	md	-1.03 percent		-1.54 to -0.52		hypothetical; other; region:brazil; R0014802:Supplement Table S11
30	A2 vs A3	md	-1.01 percent		-1.28 to -0.74		hypothetical; other; region:china_female; R0014802:Supplement Table S13
30	A2 vs A3	md	-0.80 percent		-1.01 to -0.58		hypothetical; other; region:china_male; R0014802:Supplement Table S13
30	A2	change	-1.8 percent				hypothetical; other; region:china; R0014802:Supplement Table S9
30	A2 vs A3	md	-0.87 percent		-1.04 to -0.70		hypothetical; other; region:china; R0014802:Supplement Table S9
30	A2 vs A3	md	-0.79 percent		-1.06 to -0.51		hypothetical; other; region:other_countries; R0014802:Supplement Table S10
30	A2	change	-1.8 percent				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A2 vs A3	md	-0.88 percent		-1.27 to -0.50		hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A2 vs A3	md	-0.90 percent		-1.33 to -0.48		hypothetical; other; region:republic_of_korea; R0014802:Supplement Table S11
30	A2 vs A3	md	-0.34 percent		-0.97 to 0.29		hypothetical; other; region:south_africa; R0014802:Supplement Table S11
30	A2 vs A3	md	-0.42 percent		-1.27 to 0.42		hypothetical; other; region:ukraine; R0014802:Supplement Table S11
30	A2 vs A3	md	-0.92 percent		-1.16 to -0.68		hypothetical; other; sex:female; R0014802:Supplement Table S12
30	A2 vs A3	md	-0.83 percent		-1.03 to -0.63		hypothetical; other; sex:male; R0014802:Supplement Table S12
30	A2	change	-1.7 percent			290	hypothetical; full analysis; R0014802:Table 2
30	A2	change	-1.8 percent	0.9		290	hypothetical; full analysis; registry:outcomes
30	A2 vs A3	md	-0.85 percent		-1.00 to -0.70		hypothetical; full analysis; R0014802:Table 2
30	A3	change	-0.9 percent	0.9		290	treatment policy; full analysis; registry:outcomes
30	A3	change	-0.9 percent				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A3	change	-0.9 percent			290	hypothetical; full analysis; R0014802:Table 2
30	A3	change	-1.0 percent	0.9		290	hypothetical; full analysis; registry:outcomes
30	A3	change	-0.9 percent				hypothetical; other; region:china; R0014802:Supplement Table S9

Body weight change in kilograms (diabetes) (46 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	-3.0 kg	3.8		238	hypothetical; completers; registry:outcomes
30	A1 vs A3	md	-2.48 kg		-3.06 to -1.90		hypothetical; full analysis; R0014802:Table 2
30	A1 vs A3	md	-2.30 kg		-2.84 to -1.77		hypothetical; full analysis; R0014802:Supplement Figure S6
30	A1 vs A3	md	-2.53 kg		-3.14 to -1.93		hypothetical; completers; R0014802:Supplement Figure S6
30	A1 vs A3	md	-2.31 kg		-2.87 to -1.76		hypothetical; full analysis; R0014802:Supplement Figure S6
30	A1 vs A3	md	-2.0 kg		-4.6 to 0.5		hypothetical; other; region:south_africa; R0014802:Supplement Table S11
30	A1 vs A3	md	-2.52 kg		-3.20 to -1.85		hypothetical; other; region:china; R0014802:Supplement Table S9
30	A1	change	-3.1 kg				hypothetical; other; region:china; R0014802:Supplement Table S9
30	A1 vs A3	md	-2.1 kg		-3.01 to -1.32		hypothetical; other; region:china_male; R0014802:Supplement Table S13
30	A1 vs A3	md	-2.8 kg		-4.4 to -1.1		hypothetical; other; region:republic_of_korea; R0014802:Supplement Table S11
30	A1 vs A3	md	-2.8 kg		-4.8 to -0.8		hypothetical; other; region:brazil; R0014802:Supplement Table S11
30	A1 vs A3	md	-2.1 kg		-2.87 to -1.38		hypothetical; other; sex:male; R0014802:Supplement Table S12
30	A1 vs A3	md	-2.8 kg		-3.73 to -1.92		hypothetical; other; sex:female; R0014802:Supplement Table S12
30	A1 vs A3	md	-3.15 kg		-4.79 to -1.51		hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A1 vs A3	md	-2.41 kg		-2.97 to -1.84		treatment policy; full analysis; R0014802:Supplement Figure S6
30	A1 vs A3	md	-2.33 kg		-3.05 to -1.61		treatment policy; full analysis; R0014802:Supplement Figure S6
30	A1	change	-2.7 kg				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A1 vs A3	md	-0.2 kg		-3.0 to 3.3		hypothetical; other; region:ukraine; R0014802:Supplement Table S11
30	A1 vs A3	md	-2.3 kg		-3.4 to -1.2		hypothetical; other; region:other_countries; R0014802:Supplement Table S10
30	A1 vs A3	md	-3.0 kg		-4.08 to -1.88		hypothetical; other; region:china_female; R0014802:Supplement Table S13
30	A1	change	-2.9 kg			238	hypothetical; full analysis; R0014802:Table 2
30	A2 vs A3	md	-6.0 kg		-8.0 to -4.0		hypothetical; other; region:brazil; R0014802:Supplement Table S11
30	A2	change	-4.2 kg			239	hypothetical; full analysis; R0014802:Table 2
30	A2	change	-4.2 kg	3.7		239	hypothetical; completers; registry:outcomes
30	A2 vs A3	md	-3.79 kg		-4.37 to -3.21		hypothetical; full analysis; R0014802:Table 2
30	A2 vs A3	md	-3.47 kg		-4.00 to -2.94		hypothetical; full analysis; R0014802:Supplement Figure S6
30	A2 vs A3	md	-3.71 kg		-4.31 to -3.10		hypothetical; completers; R0014802:Supplement Figure S6
30	A2 vs A3	md	-3.41 kg		-3.96 to -2.85		hypothetical; full analysis; R0014802:Supplement Figure S6
30	A2 vs A3	md	-3.56 kg		-4.13 to -3.00		treatment policy; full analysis; R0014802:Supplement Figure S6
30	A2 vs A3	md	-3.24 kg		-3.94 to -2.54		treatment policy; full analysis; R0014802:Supplement Figure S6
30	A2 vs A3	md	-3.9 kg		-5.00 to -2.86		hypothetical; other; region:china_female; R0014802:Supplement Table S13
30	A2 vs A3	md	-2.9 kg		-3.72 to -2.01		hypothetical; other; region:china_male; R0014802:Supplement Table S13
30	A2	change	-4.0 kg				hypothetical; other; region:china; R0014802:Supplement Table S9
30	A2 vs A3	md	-3.38 kg		-4.05 to -2.70		hypothetical; other; region:china; R0014802:Supplement Table S9
30	A2 vs A3	md	-4.8 kg		-5.9 to -3.7		hypothetical; other; region:other_countries; R0014802:Supplement Table S10
30	A2	change	-4.8 kg				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A2 vs A3	md	-5.26 kg		-6.89 to -3.63		hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A2 vs A3	md	-4.7 kg		-6.4 to -3.1		hypothetical; other; region:republic_of_korea; R0014802:Supplement Table S11
30	A2 vs A3	md	-3.9 kg		-6.4 to -1.5		hypothetical; other; region:south_africa; R0014802:Supplement Table S11
30	A2 vs A3	md	-2.6 kg		-5.9 to 0.7		hypothetical; other; region:ukraine; R0014802:Supplement Table S11
30	A2 vs A3	md	-4.4 kg		-5.26 to -3.47		hypothetical; other; sex:female; R0014802:Supplement Table S12
30	A2 vs A3	md	-3.2 kg		-3.94 to -2.44		hypothetical; other; sex:male; R0014802:Supplement Table S12
30	A3	change	-0.6 kg				hypothetical; other; region:china; R0014802:Supplement Table S9
30	A3	change	0.5 kg				hypothetical; full analysis; region:republic_of_korea; R0007730:Table 2
30	A3	change	-0.4 kg	2.5		253	hypothetical; completers; registry:outcomes
30	A3	change	-0.4 kg			253	hypothetical; full analysis; R0014802:Table 2

HbA1c below 7 percent (8 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1 vs A3	or	3.98	2.70 to 5.87		hypothetical; full analysis; R0014802:Figure 2
30	A1	responders	71.2		288	hypothetical; full analysis; R0014802:Figure 2
30	A1	responders	74.5		235	hypothetical; completers; registry:outcomes
30	A2 vs A3	or	7.95	5.17 to 12.21		hypothetical; full analysis; R0014802:Figure 2
30	A2	responders	82.4		290	hypothetical; full analysis; R0014802:Figure 2
30	A2	responders	84.0		238	hypothetical; completers; registry:outcomes
30	A3	responders	44.8		290	hypothetical; full analysis; R0014802:Figure 2
30	A3	responders	49.6		250	hypothetical; completers; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (6 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 287	while on treatment; safety; R0014802:Results
A1	events	2 / 287	while on treatment; safety; R0014802:Table 3
A2	events	0 / 290	while on treatment; safety; R0014802:Results
A2	events	6 / 290	while on treatment; safety; R0014802:Table 3
A3	events	4 / 290	while on treatment; safety; R0014802:Table 3
A3	events	0 / 290	while on treatment; safety; R0014802:Results

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

Arm	Statistic	Detail
A1	rate	while on treatment; safety; R0014802:Table 3
A2	rate	while on treatment; safety; R0014802:Table 3
A3	rate	while on treatment; safety; R0014802:Table 3

Systolic blood pressure change (8 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1 vs A3	md	-2.3 mmHg		-4.4 to -0.2		hypothetical; full analysis; R0014802:Table 2
30	A1	change	-3.4 mmHg			238	hypothetical; full analysis; R0014802:Table 2
30	A1	change	-3.4 mmHg	14.7		238	hypothetical; completers; registry:outcomes
30	A2 vs A3	md	-5.5 mmHg		-7.6 to -3.4		hypothetical; full analysis; R0014802:Table 2
30	A2	change	-6.6 mmHg			239	hypothetical; full analysis; R0014802:Table 2
30	A2	change	-6.5 mmHg	13.4		239	hypothetical; completers; registry:outcomes
30	A3	change	-0.9 mmHg	13.6		254	hypothetical; completers; registry:outcomes
30	A3	change	-1.1 mmHg			254	hypothetical; full analysis; R0014802:Table 2

Percent body weight change (5 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Detail
30	A1	percent change	-3.9 percent		hypothetical; full analysis; R0014802:Table 2
30	A1 vs A3	md	-3.46 percent	-4.22 to -2.69	hypothetical; full analysis; R0014802:Table 2
30	A2	percent change	-5.7 percent		hypothetical; full analysis; R0014802:Table 2
30	A2 vs A3	md	-5.28 percent	-6.04 to -4.51	hypothetical; full analysis; R0014802:Table 2
30	A3	percent change	-0.5 percent		hypothetical; full analysis; R0014802:Table 2

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	responders	34.5		288	hypothetical; full analysis; R0014802:Figure 2
30	A1	responders	36.6		238	hypothetical; completers; registry:outcomes
30	A1 vs A3	or	9.17	5.26 to 15.98		hypothetical; full analysis; R0014802:Figure 2
30	A2	responders	54.5		290	hypothetical; full analysis; R0014802:Figure 2
30	A2	responders	52.7		239	hypothetical; completers; registry:outcomes
30	A2 vs A3	or	20.49	11.81 to 35.54		hypothetical; full analysis; R0014802:Figure 2
30	A3	responders	5.5		290	hypothetical; full analysis; R0014802:Figure 2
30	A3	responders	5.9		253	hypothetical; completers; registry:outcomes

Weight loss of 10 percent or more (8 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
30	A1	responders	8.4		288	hypothetical; full analysis; R0014802:Supplement Figure S7
30	A1	responders	9.7		238	hypothetical; completers; registry:outcomes
30	A1 vs A3	or	18.70	3.59 to 97.34		hypothetical; full analysis; R0014802:Supplement Figure S7
30	A2	responders	16.2		290	hypothetical; full analysis; R0014802:Supplement Figure S7
30	A2	responders	17.2		239	hypothetical; completers; registry:outcomes
30	A2 vs A3	or	38.17	7.50 to 194.21		hypothetical; full analysis; R0014802:Supplement Figure S7
30	A3	responders	0.4		253	hypothetical; completers; registry:outcomes
30	A3	responders	0.3		290	hypothetical; full analysis; R0014802:Supplement Figure S7

All cause mortality (6 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 287	while on treatment; safety; R0014802:Table 3
A1	events	0 / 35	not stated; safety; region:republic_of_korea; R0007730:Table 3
A2	events	1 / 290	while on treatment; safety; R0014802:Table 3
A2	events	1 / 40	not stated; safety; region:republic_of_korea; R0007730:Table 3
A3	events	0 / 290	while on treatment; safety; R0014802:Table 3
A3	events	0 / 35	not stated; safety; region:republic_of_korea; R0007730:Table 3

SF-36 physical component summary change (5 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	1.3 points	5.9		246	hypothetical; completers; registry:outcomes
30	A1 vs A3	md	0.97 points		0.04 to 1.90		hypothetical; full analysis; R0014802:Supplement Figure S11
30	A2	change	1.1 points	6.0		249	hypothetical; completers; registry:outcomes
30	A2 vs A3	md	0.78 points		-0.14 to 1.71		hypothetical; full analysis; R0014802:Supplement Figure S11
30	A3	change	0.0 points	5.8		257	hypothetical; completers; registry:outcomes

Physical functioning (any instrument) (5 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
30	A1	change	0.6 points	5.6		246	hypothetical; completers; registry:outcomes
30	A1 vs A3	md	0.39 points		-0.58 to 1.36		hypothetical; full analysis; R0014802:Supplement Figure S11
30	A2	change	0.9 points	7.4		249	hypothetical; completers; registry:outcomes
30	A2 vs A3	md	0.55 points		-0.42 to 1.52		hypothetical; full analysis; R0014802:Supplement Figure S11
30	A3	change	-0.3 points	5.5		257	hypothetical; completers; registry:outcomes

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	4.9 points	7.2		246	hypothetical; completers; registry:outcomes
30	A1 vs A3	md	1.34 points		0.57 to 2.11		hypothetical; full analysis; R0014802:Supplement Figure S10
30	A2	change	5.1 points	6.3		249	hypothetical; completers; registry:outcomes
30	A2 vs A3	md	1.03 points		0.26 to 1.79		hypothetical; full analysis; R0014802:Supplement Figure S10
30	A3	change	3.7 points	7.2		257	hypothetical; completers; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	18 / 287	while on treatment; safety; R0014802:Table 3
A2	events	18 / 290	while on treatment; safety; R0014802:Table 3
A2	events	19 / 290	while on treatment; safety; registry:adverse_events
A3	events	12 / 290	while on treatment; safety; R0014802:Table 3

Discontinuation due to adverse events (3 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	17 / 287	while on treatment; safety; R0014802:Table 3
A2	events	31 / 290	while on treatment; safety; R0014802:Table 3
A3	events	6 / 290	while on treatment; safety; R0014802:Table 3

Nausea (3 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	22 / 287	while on treatment; safety; R0014802:Table 3
A2	events	39 / 290	while on treatment; safety; R0014802:Table 3
A3	events	5 / 290	while on treatment; safety; R0014802:Table 3

Vomiting (3 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	14 / 287	while on treatment; safety; R0014802:Table 3
A2	events	19 / 290	while on treatment; safety; R0014802:Table 3
A3	events	3 / 290	while on treatment; safety; R0014802:Table 3

Diarrhea (3 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	58 / 287	while on treatment; safety; R0014802:Table 3
A2	events	49 / 290	while on treatment; safety; R0014802:Table 3
A3	events	20 / 290	while on treatment; safety; R0014802:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	10 / 287	while on treatment; safety; R0014802:Table 3
A2	events	21 / 290	while on treatment; safety; R0014802:Table 3
A3	events	1 / 290	while on treatment; safety; R0014802:Table 3

Gallbladder and biliary disease (18 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 287	treatment policy; safety; gallbladder polyp; R0014802:Supplement Table S4
A1	events	0 / 287	while on treatment; safety; cholecystitis acute; registry:adverse_events
A1	events	0 / 287	while on treatment; safety; cholelithiasis; registry:adverse_events
A1	events	1 / 287	while on treatment; safety; biliary colic; registry:adverse_events
A1	events	0 / 287	while on treatment; safety; cholecystitis; registry:adverse_events
A1	events	0 / 287	while on treatment; safety; cholecystitis chronic; registry:adverse_events
A2	events	1 / 290	while on treatment; safety; cholecystitis acute; registry:adverse_events
A2	events	0 / 290	treatment policy; safety; gallbladder polyp; R0014802:Supplement Table S4
A2	events	0 / 290	while on treatment; safety; biliary colic; registry:adverse_events
A2	events	1 / 290	while on treatment; safety; cholecystitis chronic; registry:adverse_events
A2	events	1 / 290	while on treatment; safety; cholecystitis; registry:adverse_events
A2	events	1 / 290	while on treatment; safety; cholelithiasis; registry:adverse_events
A3	events	0 / 290	while on treatment; safety; cholecystitis acute; registry:adverse_events
A3	events	0 / 290	while on treatment; safety; cholecystitis chronic; registry:adverse_events
A3	events	0 / 290	while on treatment; safety; cholecystitis; registry:adverse_events
A3	events	2 / 290	treatment policy; safety; gallbladder polyp; R0014802:Supplement Table S4
A3	events	0 / 290	while on treatment; safety; biliary colic; registry:adverse_events
A3	events	0 / 290	while on treatment; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 287	while on treatment; safety; R0014802:Table 3
A1	events	0 / 287	while on treatment; safety; oedematous pancreatitis; registry:adverse_events
A2	events	1 / 290	while on treatment; safety; R0014802:Table 3
A2	events	1 / 290	while on treatment; safety; oedematous pancreatitis; registry:adverse_events
A3	events	0 / 290	while on treatment; safety; R0014802:Table 3
A3	events	0 / 290	while on treatment; safety; oedematous pancreatitis; registry:adverse_events

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 287	treatment policy; safety; R0014802:Table 3
	A2	events				0 / 290	treatment policy; safety; R0014802:Table 3

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 287	treatment policy; safety; R0014802:Table 3
	A2	events				0 / 290	treatment policy; safety; R0014802:Table 3

Diabetic retinopathy complications (9 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	21 / 287	treatment policy; safety; diabetic retinopathy; R0014802:Table 3
A1	events	19 / 287	treatment policy; safety; diabetic retinopathy; R0014802:Results
A1	events	18 / 287	while on treatment; safety; diabetic retinopathy; registry:adverse_events
A1	events	1 / 287	while on treatment; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 290	while on treatment; safety; diabetic retinopathy; registry:adverse_events
A2	events	14 / 290	treatment policy; safety; diabetic retinopathy; R0014802:Results
A2	events	15 / 290	treatment policy; safety; diabetic retinopathy; R0014802:Table 3
A3	events	10 / 290	treatment policy; safety; diabetic retinopathy; R0014802:Table 3
A3	events	0 / 290	while on treatment; safety; diabetic retinopathy; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 287	while on treatment; safety; R0014802:Results
	A3	events				0 / 290	while on treatment; safety; R0014802:Table 3

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 287	treatment policy; safety; R0014802:Table 3
	A2	events				0 / 290	treatment policy; safety; R0014802:Table 3

Any cancer (3 lines; O39)

Arm	Statistic	Events / N	Detail
A1	events	0 / 287	treatment policy; safety; R0014802:Table 3
A2	events	0 / 290	treatment policy; safety; R0014802:Table 3
A3	events	2 / 290	treatment policy; safety; R0014802:Table 3