parallel randomized trial

SURPASS J-mono

A Phase 3 Study of Tirzepatide Monotherapy Compared to Dulaglutide 0.75 mg in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes (adults)NCT03861052S000239

Design

Randomized: 636
Start year: 2019
Treatment: 52 weeks, follow-up 56 weeks
Countries: Japan (46 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: Japanese adults 20 or older; BMI 23 or more; HbA1c 7.0 to 10.0 percent; drug naive or oral monotherapy washed out

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: hypothetical
Analysis population: modified itt
Missing data: MMRM

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Tirzepatide 5 mg subcutaneous once weekly Tirzepatide 5 mg	no glucose lowering drug (naive or washed out); lifestyle: none	159	159	144
A2	Tirzepatide 10 mg subcutaneous once weekly Tirzepatide 10 mg	no glucose lowering drug (naive or washed out); lifestyle: none	158	158	135
A3	Tirzepatide 15 mg subcutaneous once weekly Tirzepatide 15 mg	no glucose lowering drug (naive or washed out); lifestyle: none	160	160	136
A4	Dulaglutide 0.75 mg subcutaneous once weekly Dulaglutide 0.75 mg	no glucose lowering drug (naive or washed out); lifestyle: none	159	159	145

Baseline characteristics

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

Characteristic	Statistic	Tirzepatide 5 mg subcutaneous once weekly A1	Tirzepatide 10 mg subcutaneous once weekly A2	Tirzepatide 15 mg subcutaneous once weekly A3	Dulaglutide 0.75 mg subcutaneous once weekly A4
age: 65 or older	n	39	35	36	48
age: 65 or older	percent	24.5	22.2	22.5	30.2
age	mean (years)	56.8	56.2	56.0	57.5
age	sd (years)	10.1	10.3	10.7	10.2
asian	n	159	158	160	159
black	n	0	0	0	0
bmi	mean (kg/m2)	28.6	28.0	28.1	27.8
bmi	sd (kg/m2)	5.4	4.1	4.4	3.7
diabetes duration	mean (years)	5.5	6.0	6.0	6.3
diabetes duration	median (years)	4.5	5.1	5.1	5.0
diabetes duration	q1 (years)	2.1	2.2	2.2	1.9
diabetes duration	q3 (years)	7.5	8.4	8.4	8.4
diabetes duration	sd (years)	4.4	5.0	5.4	5.9
egfr	mean (mL/min/1.73 m2)	76.6	79.0	78.7	78.2
egfr	median (mL/min/1.73 m2)	78	80	80	79
egfr	q1 (mL/min/1.73 m2)	68	72	71	71
egfr	q3 (mL/min/1.73 m2)	86	86	86	86
egfr	sd (mL/min/1.73 m2)	13.2	11.3	12.0	11.2
female	n	46	39	28	42
female	percent	29	25	18	26
hba1c: 8.5 or less	n	108	106	109	110
hba1c: 8.5 or less	percent	68	67	68	69
hba1c: more than 8.5	n	51	52	51	49
hba1c: more than 8.5	percent	32	33	32	31
hba1c	mean (percent)	8.2	8.2	8.2	8.2
hba1c	sd (percent)	0.9	0.9	0.9	0.9
other race american indian alaska native	n	0	0	0	0
other race japanese	n	159	158	160	159
other race japanese	percent	100	100	100	100
other race multiple	n	0	0	0	0
other race native hawaiian pacific islander	n	0	0	0	0
sbp	mean (mmHg)	130.2	130.0	132.2	130.6
sbp	sd (mmHg)	12.7	15.6	13.8	15.4
waist	mean (cm)	97.1	96.3	96.5	94.9
waist	sd (cm)	11.6	9.2	10.4	9.1
weight	mean (kg)	78.5	78.9	78.9	76.5
weight	sd (kg)	16.3	13.7	14.3	13.2
white	n	0	0	0	0

Results

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

HbA1c change (22 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-2.36 percent	0.06		145	hypothetical; modified itt; R0012580:Supplement Table S3
24	A2	change	-2.54 percent	0.06		141	hypothetical; modified itt; R0012580:Supplement Table S3
24	A3	change	-2.69 percent	0.06		144	hypothetical; modified itt; R0012580:Supplement Table S3
24	A4	change	-1.55 percent	0.06		151	hypothetical; modified itt; R0012580:Supplement Table S3
40	A1	change	-2.39 percent	0.07		143	hypothetical; modified itt; R0012580:Supplement Table S3
40	A2	change	-2.57 percent	0.07		139	hypothetical; modified itt; R0012580:Supplement Table S3
40	A3	change	-2.78 percent	0.07		140	hypothetical; modified itt; R0012580:Supplement Table S3
40	A4	change	-1.36 percent	0.06		144	hypothetical; modified itt; R0012580:Supplement Table S3
52	A1	change	-2.24 percent	0.068		159	treatment policy; full analysis; R0012580:Supplement Table S2
52	A1	change	-2.4 percent	0.1		142	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	md	-1.1 percent		-1.3 to -0.9		hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	md	-0.97 percent		-1.16 to -0.78		treatment policy; full analysis; R0012580:Supplement Table S2
52	A2 vs A4	md	-1.10 percent		-1.29 to -0.90		treatment policy; full analysis; R0012580:Supplement Table S2
52	A2	change	-2.36 percent	0.069		158	treatment policy; full analysis; R0012580:Supplement Table S2
52	A2 vs A4	md	-1.3 percent		-1.5 to -1.1		hypothetical; modified itt; R0012580:Table 2
52	A2	change	-2.6 percent	0.1		135	hypothetical; modified itt; R0012580:Table 2
52	A3	change	-2.8 percent	0.1		134	hypothetical; modified itt; R0012580:Table 2
52	A3 vs A4	md	-1.5 percent		-1.7 to -1.4		hypothetical; modified itt; R0012580:Table 2
52	A3	change	-2.57 percent	0.067		160	treatment policy; full analysis; R0012580:Supplement Table S2
52	A3 vs A4	md	-1.49 percent		-1.49 to -1.11		treatment policy; full analysis; R0012580:Supplement Table S2
52	A4	change	-1.3 percent	0.1		138	hypothetical; modified itt; R0012580:Table 2
52	A4	change	-1.27 percent	0.070		159	treatment policy; full analysis; R0012580:Supplement Table S2

Body weight change in kilograms (diabetes) (49 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
20	A1	change	-4.3 kg	0.28		144	hypothetical; modified itt; R0012580:Supplement Table S9
20	A1 vs A4	md	-4.2 kg		-5.0 to -3.4		hypothetical; modified itt; R0012580:Supplement Table S9
20	A2	change	-6.1 kg	0.28		141	hypothetical; modified itt; R0012580:Supplement Table S9
20	A2 vs A4	md	-6.0 kg		-6.8 to -5.3		hypothetical; modified itt; R0012580:Supplement Table S9
20	A3	change	-6.4 kg	0.28		147	hypothetical; modified itt; R0012580:Supplement Table S9
20	A3 vs A4	md	-6.2 kg		-7.0 to -5.5		hypothetical; modified itt; R0012580:Supplement Table S9
20	A4	change	-0.1 kg	0.28		151	hypothetical; modified itt; R0012580:Supplement Table S9
24	A1 vs A4	md	-4.6 kg		-5.5 to -3.8		hypothetical; modified itt; R0012580:Supplement Table S9
24	A1	change	-4.7 kg	0.31		144	hypothetical; modified itt; R0012580:Supplement Table S9
24	A2 vs A4	md	-6.5 kg		-7.3 to -5.7		hypothetical; modified itt; R0012580:Supplement Table S9
24	A2	change	-6.6 kg	0.31		141	hypothetical; modified itt; R0012580:Supplement Table S9
24	A3	change	-7.6 kg	0.30		144	hypothetical; modified itt; R0012580:Supplement Table S9
24	A3 vs A4	md	-7.5 kg		-8.4 to -6.7		hypothetical; modified itt; R0012580:Supplement Table S9
24	A4	change	-0.1 kg	0.30		149	hypothetical; modified itt; R0012580:Supplement Table S9
32	A1	change	-5.1 kg	0.34		144	hypothetical; modified itt; R0012580:Supplement Table S9
32	A1 vs A4	md	-4.9 kg		-5.8 to -3.9		hypothetical; modified itt; R0012580:Supplement Table S9
32	A2	change	-7.5 kg	0.35		140	hypothetical; modified itt; R0012580:Supplement Table S9
32	A2 vs A4	md	-7.3 kg		-8.3 to -6.4		hypothetical; modified itt; R0012580:Supplement Table S9
32	A3	change	-9.2 kg	0.34		142	hypothetical; modified itt; R0012580:Supplement Table S9
32	A3 vs A4	md	-9.0 kg		-9.9 to -8.0		hypothetical; modified itt; R0012580:Supplement Table S9
32	A4	change	-0.2 kg	0.34		144	hypothetical; modified itt; R0012580:Supplement Table S9
40	A1	change	-5.5 kg	0.38		143	hypothetical; modified itt; R0012580:Supplement Table S9
40	A1 vs A4	md	-5.1 kg		-6.2 to -4.1		hypothetical; modified itt; R0012580:Supplement Table S9
40	A2	change	-8.1 kg	0.39		138	hypothetical; modified itt; R0012580:Supplement Table S9
40	A2 vs A4	md	-7.7 kg		-8.7 to -6.6		hypothetical; modified itt; R0012580:Supplement Table S9
40	A3	change	-10.0 kg	0.38		140	hypothetical; modified itt; R0012580:Supplement Table S9
40	A3 vs A4	md	-9.6 kg		-10.7 to -8.6		hypothetical; modified itt; R0012580:Supplement Table S9
40	A4	change	-0.4 kg	0.38		143	hypothetical; modified itt; R0012580:Supplement Table S9
48	A1	change	-5.6 kg	0.40		142	hypothetical; modified itt; R0012580:Supplement Table S9
48	A1 vs A4	md	-5.3 kg		-6.4 to -4.2		hypothetical; modified itt; R0012580:Supplement Table S9
48	A2 vs A4	md	-7.9 kg		-9.0 to -6.8		hypothetical; modified itt; R0012580:Supplement Table S9
48	A2	change	-8.2 kg	0.40		135	hypothetical; modified itt; R0012580:Supplement Table S9
48	A3	change	-10.5 kg	0.40		136	hypothetical; modified itt; R0012580:Supplement Table S9
48	A3 vs A4	md	-10.2 kg		-11.3 to -9.1		hypothetical; modified itt; R0012580:Supplement Table S9
48	A4	change	-0.3 kg	0.39		139	hypothetical; modified itt; R0012580:Supplement Table S9
52	A1	change	-5.4 kg			159	treatment policy; full analysis; R0012580:Supplement Table S2
52	A1	change	-5.8 kg	0.4		143	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	md	-5.2 kg		-6.4 to -4.1		hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	md	-4.9 kg		-6.1 to -3.8		treatment policy; full analysis; R0012580:Supplement Table S2
52	A2	change	-8.5 kg	0.4		135	hypothetical; modified itt; R0012580:Table 2
52	A2	change	-7.2 kg			158	treatment policy; full analysis; R0012580:Supplement Table S2
52	A2 vs A4	md	-6.8 kg		-8.0 to -5.6		treatment policy; full analysis; R0012580:Supplement Table S2
52	A2 vs A4	md	-7.9 kg		-9.1 to -6.8		hypothetical; modified itt; R0012580:Table 2
52	A3 vs A4	md	-10.1 kg		-11.3 to -9.0		hypothetical; modified itt; R0012580:Table 2
52	A3	change	-10.7 kg	0.4		134	hypothetical; modified itt; R0012580:Table 2
52	A3	change	-9.4 kg			160	treatment policy; full analysis; R0012580:Supplement Table S2
52	A3 vs A4	md	-8.9 kg		-10.1 to -7.8		treatment policy; full analysis; R0012580:Supplement Table S2
52	A4	change	-0.5 kg	0.4		138	hypothetical; modified itt; R0012580:Table 2
52	A4	change	-0.4 kg			159	treatment policy; full analysis; R0012580:Supplement Table S2

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	94		158	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	or	9.89	4.53 to 21.55		hypothetical; modified itt; R0012580:Supplement Table S5
52	A2	responders	97		156	hypothetical; modified itt; R0012580:Table 2
52	A2 vs A4	or	20.57	7.73 to 54.71		hypothetical; modified itt; R0012580:Supplement Table S5
52	A3 vs A4	or	85.31	15.80 to 460.58		hypothetical; modified itt; R0012580:Supplement Table S5
52	A3	responders	99		159	hypothetical; modified itt; R0012580:Table 2
52	A4	responders	67		159	hypothetical; modified itt; R0012580:Table 2

Level 2 or 3 hypoglycemia (participants) (12 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A2	events	3 / 158	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; R0012580:Table 3
A3	events	2 / 160	treatment policy; safety; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; R0012580:Table 3
A3	events	8 / 160	treatment policy; safety; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3
A4	events	1 / 159	treatment policy; safety; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3

Level 2 or 3 hypoglycemia (episode rate) (8 lines; O04B)

Arm	Statistic	Estimate	Events / N	Detail
A1	rate		159	treatment policy; safety; R0012580:Table 3
A1	rate	0	159	not stated; modified itt; registry:outcomes
A2	rate		158	treatment policy; safety; R0012580:Table 3
A2	rate	0	158	not stated; modified itt; registry:outcomes
A3	rate	0.012	160	not stated; modified itt; registry:outcomes
A3	rate		160	treatment policy; safety; R0012580:Results
A4	rate		159	treatment policy; safety; R0012580:Table 3
A4	rate	0	159	not stated; modified itt; registry:outcomes

Systolic blood pressure change (4 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Detail
52	A1	change	-6.5 mmHg	0.98	treatment policy; safety; R0012580:Supplement Table S17
52	A2	change	-8.8 mmHg	0.99	treatment policy; safety; R0012580:Supplement Table S17
52	A3	change	-11.0 mmHg	0.98	treatment policy; safety; R0012580:Supplement Table S17
52	A4	change	-1.4 mmHg	0.98	treatment policy; safety; R0012580:Supplement Table S17

Percent body weight change (24 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
20	A1	percent change	-5.7 percent	0.37	144	hypothetical; modified itt; R0012580:Supplement Table S9
20	A2	percent change	-7.9 percent	0.37	141	hypothetical; modified itt; R0012580:Supplement Table S9
20	A3	percent change	-8.4 percent	0.36	147	hypothetical; modified itt; R0012580:Supplement Table S9
20	A4	percent change	-0.2 percent	0.36	151	hypothetical; modified itt; R0012580:Supplement Table S9
24	A1	percent change	-6.3 percent	0.40	144	hypothetical; modified itt; R0012580:Supplement Table S9
24	A2	percent change	-8.5 percent	0.41	141	hypothetical; modified itt; R0012580:Supplement Table S9
24	A3	percent change	-10.0 percent	0.40	144	hypothetical; modified itt; R0012580:Supplement Table S9
24	A4	percent change	-0.1 percent	0.40	149	hypothetical; modified itt; R0012580:Supplement Table S9
32	A1	percent change	-6.8 percent	0.45	144	hypothetical; modified itt; R0012580:Supplement Table S9
32	A2	percent change	-9.7 percent	0.45	140	hypothetical; modified itt; R0012580:Supplement Table S9
32	A3	percent change	-11.9 percent	0.45	142	hypothetical; modified itt; R0012580:Supplement Table S9
32	A4	percent change	-0.3 percent	0.45	144	hypothetical; modified itt; R0012580:Supplement Table S9
40	A1	percent change	-7.4 percent	0.50	143	hypothetical; modified itt; R0012580:Supplement Table S9
40	A2	percent change	-10.4 percent	0.51	138	hypothetical; modified itt; R0012580:Supplement Table S9
40	A3	percent change	-13.1 percent	0.50	140	hypothetical; modified itt; R0012580:Supplement Table S9
40	A4	percent change	-0.5 percent	0.50	143	hypothetical; modified itt; R0012580:Supplement Table S9
48	A1	percent change	-7.6 percent	0.52	142	hypothetical; modified itt; R0012580:Supplement Table S9
48	A2	percent change	-10.7 percent	0.53	135	hypothetical; modified itt; R0012580:Supplement Table S9
48	A3	percent change	-13.7 percent	0.52	136	hypothetical; modified itt; R0012580:Supplement Table S9
48	A4	percent change	-0.4 percent	0.52	139	hypothetical; modified itt; R0012580:Supplement Table S9
52	A1	percent change	-7.8 percent	0.55	143	hypothetical; modified itt; R0012580:Supplement Table S9
52	A2	percent change	-11.0 percent	0.55	135	hypothetical; modified itt; R0012580:Supplement Table S9
52	A3	percent change	-13.9 percent	0.54	134	hypothetical; modified itt; R0012580:Supplement Table S9
52	A4	percent change	-0.7 percent	0.54	138	hypothetical; modified itt; R0012580:Supplement Table S9

Weight loss of 5 percent or more (7 lines; O11A)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	61		158	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	or	14.44	7.88 to 26.46		hypothetical; modified itt; R0012580:Supplement Table S11
52	A2	responders	82		156	hypothetical; modified itt; R0012580:Table 2
52	A2 vs A4	or	44.96	23.12 to 87.45		hypothetical; modified itt; R0012580:Supplement Table S11
52	A3	responders	89		159	hypothetical; modified itt; R0012580:Table 2
52	A3 vs A4	or	82.67	39.84 to 171.52		hypothetical; modified itt; R0012580:Supplement Table S11
52	A4	responders	11		159	hypothetical; modified itt; R0012580:Table 2

Weight loss of 10 percent or more (7 lines; O11B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	34		158	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	or	16.68	6.64 to 41.87		hypothetical; modified itt; R0012580:Supplement Table S11
52	A2	responders	50		156	hypothetical; modified itt; R0012580:Table 2
52	A2 vs A4	or	35.94	14.30 to 90.33		hypothetical; modified itt; R0012580:Supplement Table S11
52	A3	responders	67		159	hypothetical; modified itt; R0012580:Table 2
52	A3 vs A4	or	74.89	29.48 to 190.25		hypothetical; modified itt; R0012580:Supplement Table S11
52	A4	responders	3		159	hypothetical; modified itt; R0012580:Table 2

Weight loss of 15 percent or more (7 lines; O11C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	16		158	hypothetical; modified itt; R0012580:Table 2
52	A1 vs A4	or	23.44	4.45 to 123.45		hypothetical; modified itt; R0012580:Supplement Table S11
52	A2	responders	26		156	hypothetical; modified itt; R0012580:Table 2
52	A2 vs A4	or	44.84	8.62 to 233.39		hypothetical; modified itt; R0012580:Supplement Table S11
52	A3	responders	45		159	hypothetical; modified itt; R0012580:Table 2
52	A3 vs A4	or	110.89	21.44 to 573.36		hypothetical; modified itt; R0012580:Supplement Table S11
52	A4	responders	0.63		159	hypothetical; modified itt; R0012580:Supplement Table S11

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3

Four point MACE including unstable angina (4 lines; O21B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 159	treatment policy; safety; R0012580:Table 3
A2	events	3 / 158	treatment policy; safety; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; R0012580:Table 3
A4	events	2 / 159	treatment policy; safety; R0012580:Table 3

Hospitalization for heart failure (4 lines; O23)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; cardiac failure; R0012580:Supplement Table S16
A2	events	0 / 158	treatment policy; safety; cardiac failure; R0012580:Supplement Table S16
A3	events	0 / 160	treatment policy; safety; cardiac failure; R0012580:Supplement Table S16
A4	events	1 / 159	treatment policy; safety; cardiac failure; R0012580:Supplement Table S16

Health related quality of life total score (any instrument) (8 lines; O24C)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
40	A1	final	10.9 points	0.5	142	hypothetical; modified itt; R0013931:Supplement Table S1
40	A2	final	11.7 points	0.5	138	hypothetical; modified itt; R0013931:Supplement Table S1
40	A3	final	12.1 points	0.5	139	hypothetical; modified itt; R0013931:Supplement Table S1
40	A4	final	9.1 points	0.5	143	hypothetical; modified itt; R0013931:Supplement Table S1
52	A1	final	11.5 points	0.5	142	hypothetical; modified itt; R0013931:Supplement Table S1
52	A2	final	12.1 points	0.5	134	hypothetical; modified itt; R0013931:Supplement Table S1
52	A3	final	12.3 points	0.5	134	hypothetical; modified itt; R0013931:Supplement Table S1
52	A4	final	8.9 points	0.5	138	hypothetical; modified itt; R0013931:Supplement Table S1

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	8 / 159	treatment policy; safety; R0012580:Table 3
A2	events	10 / 158	treatment policy; safety; R0012580:Table 3
A3	events	7 / 160	treatment policy; safety; R0012580:Table 3
A4	events	14 / 159	treatment policy; safety; R0012580:Table 3

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	12 / 159	treatment policy; safety; R0012580:Table 3
A1	events	1 / 159	not stated; randomized; R0012580:Supplement Table S1
A2	events	1 / 158	not stated; randomized; R0012580:Supplement Table S1
A2	events	16 / 158	treatment policy; safety; R0012580:Table 3
A3	events	2 / 160	not stated; randomized; R0012580:Supplement Table S1
A3	events	16 / 160	treatment policy; safety; R0012580:Table 3
A4	events	4 / 159	not stated; randomized; R0012580:Supplement Table S1
A4	events	9 / 159	treatment policy; safety; R0012580:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	19 / 159	treatment policy; safety; R0012580:Table 3
A2	events	31 / 158	treatment policy; safety; R0012580:Table 3
A3	events	32 / 160	treatment policy; safety; R0012580:Table 3
A4	events	12 / 159	treatment policy; safety; R0012580:Table 3

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	13 / 159	treatment policy; safety; R0012580:Table 3
A2	events	8 / 158	treatment policy; safety; R0012580:Table 3
A3	events	19 / 160	treatment policy; safety; R0012580:Table 3
A4	events	2 / 159	treatment policy; safety; R0012580:Table 3

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	27 / 159	treatment policy; safety; R0012580:Table 3
A2	events	14 / 158	treatment policy; safety; R0012580:Table 3
A3	events	18 / 160	treatment policy; safety; R0012580:Table 3
A4	events	11 / 159	treatment policy; safety; R0012580:Table 3

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	24 / 159	treatment policy; safety; R0012580:Table 3
A2	events	28 / 158	treatment policy; safety; R0012580:Table 3
A3	events	22 / 160	treatment policy; safety; R0012580:Table 3
A4	events	17 / 159	treatment policy; safety; R0012580:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	7 / 159	treatment policy; safety; R0012580:Table 3
A2	events	4 / 158	treatment policy; safety; R0012580:Table 3
A3	events	11 / 160	treatment policy; safety; R0012580:Table 3
A4	events	1 / 159	treatment policy; safety; R0012580:Table 3

Gallbladder and biliary disease (32 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 159	treatment policy; safety; R0012580:Table 3
A1	events	1 / 159	not stated; safety; gallbladder polyp; registry:adverse_events
A1	events	0 / 159	treatment policy; safety; cholangitis acute; R0012580:Table 3
A1	events	0 / 159	treatment policy; safety; cholangitis acute; R0012580:Supplement Table S16
A1	events	0 / 159	treatment policy; safety; cholangitis; R0012580:Table 3
A1	events	0 / 159	treatment policy; safety; cholangitis; R0012580:Supplement Table S16
A1	events	1 / 159	treatment policy; safety; cholelithiasis; R0012580:Table 3
A1	events	1 / 159	treatment policy; safety; cholelithiasis; R0012580:Supplement Table S16
A2	events	1 / 158	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	0 / 158	treatment policy; safety; cholelithiasis; R0012580:Supplement Table S16
A2	events	0 / 158	treatment policy; safety; cholelithiasis; R0012580:Table 3
A2	events	1 / 158	treatment policy; safety; cholangitis acute; R0012580:Supplement Table S16
A2	events	1 / 158	treatment policy; safety; cholangitis acute; R0012580:Table 3
A2	events	1 / 158	treatment policy; safety; cholangitis; R0012580:Table 3
A2	events	1 / 158	treatment policy; safety; cholangitis; R0012580:Supplement Table S16
A3	events	0 / 160	treatment policy; safety; cholangitis acute; R0012580:Supplement Table S16
A3	events	0 / 160	treatment policy; safety; cholangitis acute; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; cholangitis; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; cholangitis; R0012580:Supplement Table S16
A3	events	2 / 160	treatment policy; safety; cholelithiasis; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; cholelithiasis; R0012580:Supplement Table S16
A3	events	2 / 160	treatment policy; safety; R0012580:Table 3
A3	events	6 / 160	not stated; safety; gallbladder polyp; registry:adverse_events
A4	events	0 / 159	not stated; safety; gallbladder polyp; registry:adverse_events
A4	events	0 / 159	treatment policy; safety; cholangitis; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; cholelithiasis; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; cholelithiasis; R0012580:Supplement Table S16
A4	events	0 / 159	treatment policy; safety; cholangitis acute; R0012580:Supplement Table S16
A4	events	0 / 159	treatment policy; safety; cholangitis acute; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; cholangitis; R0012580:Supplement Table S16
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; pancreatitis; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; pancreatitis; R0012580:Table 3
A3	events	1 / 160	treatment policy; safety; pancreatitis; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; pancreatitis; R0012580:Table 3

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 158	not stated; safety; diabetic retinopathy; registry:adverse_events
A3	events	3 / 160	not stated; safety; diabetic retinopathy; registry:adverse_events
A4	events	1 / 159	not stated; safety; diabetic retinopathy; registry:adverse_events

Death by suicide (4 lines; O35B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3

Intestinal obstruction or ileus (4 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 159	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events
A2	events	0 / 158	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events
A3	events	0 / 160	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events
A4	events	0 / 159	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events

Pancreatic cancer (4 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	0 / 159	treatment policy; safety; R0012580:Table 3
A2	events	0 / 158	treatment policy; safety; R0012580:Table 3
A3	events	0 / 160	treatment policy; safety; R0012580:Table 3
A4	events	0 / 159	treatment policy; safety; R0012580:Table 3