parallel randomized trial

NCT05759897

A 16-week Multicenter, Randomized, Double-blinded, Placebo-controlled, Parallel-group Study to Evaluate the Efficacy and Safety of HRS-7535 in Adults With Type 2 Diabetes Mellitus Inadequately Controlled on Metformin

Type 2 diabetes (adults)NCT05759897S000877

Design

Randomized: 194
Start year: 2023
Treatment: 16 weeks, follow-up 18 weeks
Countries: China (44 sites)
Sponsor: Shandong Suncadia Medicine (industry)
Eligibility: age 18 to 75; BMI 19.0 to 40.0; HbA1c 7.5 to 11.0 on stable metformin

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: hypothetical
Analysis population: full analysis
Missing data: MMRM excluding data after intercurrent events

Arms

Arm	Treatment	Background	Analyzed	Completed treatment
A1	Placebo Placebo	metformin extended release 1000 to 2000 mg/d; lifestyle: not reported	39	38
A2	Safiglipron (HRS-7535) 15 mg tablet once daily HRS-7535 15 mg	metformin extended release 1000 to 2000 mg/d; lifestyle: not reported	39	34
A3	Safiglipron (HRS-7535) 30 mg tablet once daily HRS-7535 30 mg	metformin extended release 1000 to 2000 mg/d; lifestyle: not reported	39	33
A4	Safiglipron (HRS-7535) 60 mg tablet once daily HRS-7535 60 mg	metformin extended release 1000 to 2000 mg/d; lifestyle: not reported	38	36
A5	Safiglipron (HRS-7535) 90 mg tablet once daily HRS-7535 90 mg	metformin extended release 1000 to 2000 mg/d; lifestyle: not reported	39	36

Baseline characteristics

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

Characteristic	Statistic	Placebo A1	Safiglipron (HRS-7535) 15 mg tablet once daily A2	Safiglipron (HRS-7535) 30 mg tablet once daily A3	Safiglipron (HRS-7535) 60 mg tablet once daily A4	Safiglipron (HRS-7535) 90 mg tablet once daily A5
age	mean (years)	48.9	52.4	55.5	52.2	52.4
age	sd (years)	10.4	11.1	9.4	12.2	11.4
bmi	mean (kg/m2)	27.1	26.3	25.2	27.1	27.9
bmi	sd (kg/m2)	4.0	4.0	2.8	3.5	4.0
diabetes duration	mean (years)	5.2	5.3	5.1	3.7	5.5
diabetes duration	sd (years)	5.1	4.0	4.1	3.9	5.1
egfr	mean (mL/min/1.73 m2)	107.2	107.3	101.5	104.3	105.0
egfr	sd (mL/min/1.73 m2)	14.0	14.6	14.9	12.9	15.2
female	n	16	17	13	14	19
female	percent	41.0	43.6	33.3	36.8	48.7
hba1c	mean (percent)	8.4	8.5	8.6	8.5	8.6
hba1c	sd (percent)	0.6	0.7	0.8	0.7	0.8
sbp	mean (mmHg)	123.3	122.9	125.0	122.8	123.6
sbp	sd (mmHg)	12.4	11.8	11.8	9.4	10.2
waist	mean (cm)	95.4	94.0	93.3	95.9	96.5
waist	sd (cm)	10.2	7.7	8.6	8.8	8.9
weight	mean (kg)	75.3	72.6	69.1	75.3	74.9
weight	sd (kg)	13.3	13.3	9.3	12.7	12.6

Analyses this trial contributes to

Results

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

HbA1c change (90 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	change	-0.23 percent	-0.72 to 0.25	13	hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A1	change	-0.24 percent	-0.64 to 0.16	19	hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A1	change	0.06 percent	-0.53 to 0.65	9	hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A1	change	-0.44 percent	-0.87 to -0.02	17	hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A1	change	-0.38 percent	-0.71 to -0.05	38	treatment policy; full analysis; R0002101:Supplement eTable 3
16	A1	change	-0.25 percent	-0.75 to 0.26	13	hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A1	change	0.80 percent	-0.61 to 2.22	1	hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A1	change	-0.25 percent	-0.81 to 0.31	7	hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A1	change	-0.25 percent	-0.60 to 0.09	26	hypothetical; full analysis; R0002101:Table 2
16	A1	change	-0.30 percent	-0.64 to 0.04	25	hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A2	change	-1.08 percent	-1.40 to -0.75	34	treatment policy; full analysis; R0002101:Supplement eTable 3
16	A2 vs A1	md	-0.70 percent	-1.16 to -0.24		treatment policy; full analysis; R0002101:Supplement eTable 3
16	A2	change	-1.19 percent	-1.54 to -0.84	33	hypothetical; full analysis; R0002101:Table 2
16	A2 vs A1	md	-0.94 percent	-1.43 to -0.45		hypothetical; full analysis; R0002101:Table 2
16	A2	change	-1.00 percent	-1.51 to -0.49	15	hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A2 vs A1	md	-0.93 percent	-1.51 to -0.35		hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A2 vs A1	md	-1.01 percent	-1.78 to -0.24		hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A2	change	-1.25 percent	-1.78 to -0.73	12	hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A2	change	-1.17 percent	-1.59 to -0.75	21	hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A2	change	-0.69 percent	-1.51 to 0.12	6	hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A2 vs A1	md	-1.50 percent	-3.12 to 0.12		hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A2 vs A1	md	-0.75 percent	-1.47 to -0.03		hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A2 vs A1	md	-1.12 percent	-1.81 to -0.42		hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A2 vs A1	md	-1.34 percent	-2.08 to -0.61		hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A2	change	-1.28 percent	-1.72 to -0.84	21	hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A2	change	-1.35 percent	-1.85 to -0.85	18	hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A2 vs A1	md	-1.00 percent	-1.51 to -0.49		hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A2	change	-1.03 percent	-1.62 to -0.45	12	hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A2 vs A1	md	-0.59 percent	-1.31 to 0.14		hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A2	change	-1.30 percent	-1.67 to -0.92	27	hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A3	change	-1.22 percent	-1.68 to -0.77	17	hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A3	change	-1.59 percent	-1.94 to -1.24	30	hypothetical; full analysis; R0002101:Table 2
16	A3 vs A1	md	-1.34 percent	-1.83 to -0.84		hypothetical; full analysis; R0002101:Table 2
16	A3	change	-1.39 percent	-1.72 to -1.06	34	treatment policy; full analysis; R0002101:Supplement eTable 3
16	A3 vs A1	md	-1.01 percent	-1.48 to -0.55		treatment policy; full analysis; R0002101:Supplement eTable 3
16	A3	change	-0.67 percent	-1.59 to 0.25	3	hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.47 percent	-3.14 to 0.20		hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A3	change	-1.73 percent	-2.10 to -1.37	27	hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.43 percent	-1.94 to -0.94		hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A3	change	-1.73 percent	-2.32 to -1.15	11	hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.29 percent	-2.02 to -0.57		hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A3	change	-1.53 percent	-1.96 to -1.09	19	hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.59 percent	-2.32 to -0.85		hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A3 vs A1	md	-0.98 percent	-1.59 to -0.38		hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A3	change	-2.06 percent	-2.54 to -1.58	13	hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.81 percent	-2.55 to -1.07		hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A3	change	-1.43 percent	-2.02 to -0.84	10	hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.18 percent	-1.96 to -0.41		hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A3	change	-1.67 percent	-2.14 to -1.21	20	hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A3 vs A1	md	-1.44 percent	-2.11 to -0.77		hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.07 percent	-1.63 to -0.51		hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.54 percent	-2.33 to -0.76		hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.37 percent	-1.83 to -0.90		treatment policy; full analysis; R0002101:Supplement eTable 3
16	A4	change	-1.74 percent	-2.08 to -1.41	36	treatment policy; full analysis; R0002101:Supplement eTable 3
16	A4	change	-2.14 percent	-2.51 to -1.77	28	hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A4	change	-0.80 percent	-1.51 to -0.10	8	hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.84 percent	-2.35 to -1.34		hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A4	change	-1.55 percent	-2.09 to -1.00	13	hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.30 percent	-2.04 to -0.56		hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.61 percent	-3.20 to -0.01		hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A4	change	-1.99 percent	-2.45 to -1.54	23	hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.76 percent	-2.42 to -1.09		hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.57 percent	-2.05 to -1.08		hypothetical; full analysis; R0002101:Table 2
16	A4	change	-1.82 percent	-2.16 to -1.48	36	hypothetical; full analysis; R0002101:Table 2
16	A4	change	-2.09 percent	-2.54 to -1.64	21	hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A4 vs A1	md	-1.65 percent	-2.27 to -1.02		hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A4	change	-1.31 percent	-1.70 to -0.92	24	hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A4	change	-1.48 percent	-2.0 to -0.96	15	hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A4	change	-2.82 percent	-3.37 to -2.28	12	hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A4 vs A1	md	-2.57 percent	-3.36 to -1.79		hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.11 percent	-1.71 to -0.50		hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A5	change	-1.71 percent	-2.25 to -1.18	14	hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.78 percent	-2.58 to -0.97		hypothetical; full analysis; bmi:less_than_26; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.52 percent	-3.16 to 0.12		hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A5	change	-0.72 percent	-1.55 to 0.11	6	hypothetical; full analysis; age:65_or_more; R0002101:Supplement eTable 2
16	A5	change	-0.96 percent	-1.39 to -0.54	19	hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A5 vs A1	md	-0.72 percent	-1.31 to -0.14		hypothetical; full analysis; hba1c:8.5_or_less; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.13 percent	-1.60 to -0.67		treatment policy; full analysis; R0002101:Supplement eTable 3
16	A5	change	-1.51 percent	-1.84 to -1.18	37	treatment policy; full analysis; R0002101:Supplement eTable 3
16	A5	change	-1.72 percent	-2.21 to -1.23	18	hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A5	change	-2.50 percent	-2.96 to -2.04	16	hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A5 vs A1	md	-2.25 percent	-2.97 to -1.525		hypothetical; full analysis; hba1c:more_than_8.5; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.39 percent	-1.87 to -0.91		hypothetical; full analysis; R0002101:Table 2
16	A5 vs A1	md	-1.48 percent	-2.18 to -0.79		hypothetical; full analysis; sex:male; R0002101:Supplement eTable 2
16	A5	change	-1.53 percent	-2.0 to -1.06	17	hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.28 percent	-1.97 to -0.59		hypothetical; full analysis; sex:female; R0002101:Supplement eTable 2
16	A5	change	-1.64 percent	-1.97 to -1.30	35	hypothetical; full analysis; R0002101:Table 2
16	A5	change	-1.55 percent	-1.98 to -1.12	21	hypothetical; full analysis; bmi:26_or_more; R0002101:Supplement eTable 2
16	A5 vs A1	md	-1.51 percent	-2.00 to -1.025		hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2
16	A5	change	-1.81 percent	-2.16 to -1.46	29	hypothetical; full analysis; age:less_than_65; R0002101:Supplement eTable 2

Body weight change in kilograms (diabetes) (9 lines; O02)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	change	-1.06 kg	-1.91 to -0.22	26	hypothetical; full analysis; R0002101:Table 2
16	A2	change	-0.33 kg	-1.16 to 0.51	33	hypothetical; full analysis; R0002101:Table 2
16	A2 vs A1	md	0.74 kg	-0.45 to 1.92		hypothetical; full analysis; R0002101:Table 2
16	A3	change	-0.42 kg	-1.27 to 0.42	30	hypothetical; full analysis; R0002101:Table 2
16	A3 vs A1	md	0.64 kg	-0.56 to 1.84		hypothetical; full analysis; R0002101:Table 2
16	A4 vs A1	md	0.03 kg	-1.14 to 1.20		hypothetical; full analysis; R0002101:Table 2
16	A4	change	-1.03 kg	-1.84 to -0.23	36	hypothetical; full analysis; R0002101:Table 2
16	A5	change	-2.04 kg	-2.84 to -1.24	35	hypothetical; full analysis; R0002101:Table 2
16	A5 vs A1	md	-0.97 kg	-2.13 to 0.19		hypothetical; full analysis; R0002101:Table 2

HbA1c below 7 percent (9 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	responders	15.4	5.9 to 30.5	6 / 39	hypothetical; full analysis; R0002101:Table 2
16	A2	responders	48.7	32.4 to 65.2	19 / 39	hypothetical; full analysis; R0002101:Table 2
16	A2 vs A1	rd	33.3	14.0 to 52.7		hypothetical; full analysis; R0002101:Table 2
16	A3	responders	56.4	39.6 to 72.2	22 / 39	hypothetical; full analysis; R0002101:Table 2
16	A3 vs A1	rd	41.0	21.8 to 60.3		hypothetical; full analysis; R0002101:Table 2
16	A4	responders	63.2	46.0 to 78.2	24 / 38	hypothetical; full analysis; R0002101:Table 2
16	A4 vs A1	rd	47.8	28.7 to 66.8		hypothetical; full analysis; R0002101:Table 2
16	A5 vs A1	rd	35.9	16.6 to 55.2		hypothetical; full analysis; R0002101:Table 2
16	A5	responders	51.3	34.8 to 67.6	20 / 39	hypothetical; full analysis; R0002101:Table 2

Level 2 or 3 hypoglycemia (participants) (10 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Results
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	0 / 39	not stated; safety; R0002101:Results
A3	events	0 / 39	not stated; safety; R0002101:Results
A3	events	0 / 39	not stated; safety; R0002101:Table 3
A4	events	0 / 38	not stated; safety; R0002101:Table 3
A4	events	0 / 38	not stated; safety; R0002101:Results
A5	events	0 / 39	not stated; safety; R0002101:Results
A5	events	0 / 39	not stated; safety; R0002101:Table 3

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	Events / N	Detail
16	A1	change	-1.9 mmHg	11.6	39	not stated; other; R0002101:Supplement eTable 11
16	A2	change	-1.3 mmHg	9.6	39	not stated; other; R0002101:Supplement eTable 11
16	A3	change	-0.2 mmHg	9.8	39	not stated; other; R0002101:Supplement eTable 11
16	A4	change	0.4 mmHg	11.3	38	not stated; other; R0002101:Supplement eTable 11
16	A5	change	-3.4 mmHg	10.2	39	not stated; other; R0002101:Supplement eTable 11

Percent body weight change (9 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
16	A1	percent change	-1.30 percent	-2.46 to -0.15	33	hypothetical; full analysis; R0002101:Table 2
16	A2	percent change	-0.40 percent	-1.53 to 0.73	30	hypothetical; full analysis; R0002101:Table 2
16	A2 vs A1	md	0.90 percent	-0.71 to 2.52		hypothetical; full analysis; R0002101:Table 2
16	A3	percent change	-0.50 percent	-1.65 to 0.66	36	hypothetical; full analysis; R0002101:Table 2
16	A3 vs A1	md	0.81 percent	-0.83 to 2.44		hypothetical; full analysis; R0002101:Table 2
16	A4	percent change	-1.49 percent	-2.59 to -0.40	35	hypothetical; full analysis; R0002101:Table 2
16	A4 vs A1	md	-0.19 percent	-1.78 to 1.40		hypothetical; full analysis; R0002101:Table 2
16	A5	percent change	-2.63 percent	-3.72 to -1.54	26	hypothetical; full analysis; R0002101:Table 2
16	A5 vs A1	md	-1.32 percent	-2.91 to 0.26		hypothetical; full analysis; R0002101:Table 2

All cause mortality (5 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	0 / 39	not stated; safety; R0002101:Table 3
A3	events	1 / 39	not stated; safety; R0002101:Table 3
A4	events	0 / 38	not stated; safety; R0002101:Table 3
A5	events	0 / 39	not stated; safety; R0002101:Table 3

Serious adverse events (10 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	2 / 39	not stated; safety; R0002101:Table 3
A1	events	2 / 39	not stated; safety; R0002101:Supplement eTable 9
A2	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	0 / 39	not stated; safety; R0002101:Supplement eTable 9
A3	events	1 / 39	not stated; safety; R0002101:Supplement eTable 9
A3	events	1 / 39	not stated; safety; R0002101:Table 3
A4	events	1 / 38	not stated; safety; R0002101:Supplement eTable 9
A4	events	1 / 38	not stated; safety; R0002101:Table 3
A5	events	1 / 39	not stated; safety; R0002101:Table 3
A5	events	2 / 39	not stated; safety; R0002101:Supplement eTable 9

Discontinuation due to adverse events (5 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	3 / 39	not stated; safety; R0002101:Table 3
A3	events	2 / 39	not stated; safety; R0002101:Table 3
A4	events	0 / 38	not stated; safety; R0002101:Table 3
A5	events	2 / 39	not stated; safety; R0002101:Table 3

Nausea (5 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 39	not stated; safety; R0002101:Table 3
A2	events	3 / 39	not stated; safety; R0002101:Table 3
A3	events	3 / 39	not stated; safety; R0002101:Table 3
A4	events	13 / 38	not stated; safety; R0002101:Table 3
A5	events	8 / 39	not stated; safety; R0002101:Table 3

Vomiting (5 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	1 / 39	not stated; safety; R0002101:Table 3
A3	events	2 / 39	not stated; safety; R0002101:Table 3
A4	events	6 / 38	not stated; safety; R0002101:Table 3
A5	events	5 / 39	not stated; safety; R0002101:Table 3

Diarrhea (5 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	3 / 39	not stated; safety; R0002101:Table 3
A3	events	2 / 39	not stated; safety; R0002101:Table 3
A4	events	3 / 38	not stated; safety; R0002101:Table 3
A5	events	6 / 39	not stated; safety; R0002101:Table 3

Constipation (5 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Supplement eTable 6
A2	events	2 / 39	not stated; safety; R0002101:Supplement eTable 6
A3	events	0 / 39	not stated; safety; R0002101:Supplement eTable 6
A4	events	1 / 38	not stated; safety; R0002101:Supplement eTable 6
A5	events	2 / 39	not stated; safety; R0002101:Supplement eTable 6

Discontinuation due to gastrointestinal adverse events (10 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; diarrhea; R0002101:Supplement eTable 8
A1	events	0 / 39	not stated; safety; vomiting; R0002101:Supplement eTable 8
A2	events	1 / 39	not stated; safety; diarrhea; R0002101:Supplement eTable 8
A2	events	1 / 39	not stated; safety; vomiting; R0002101:Supplement eTable 8
A3	events	0 / 39	not stated; safety; diarrhea; R0002101:Supplement eTable 8
A3	events	1 / 39	not stated; safety; vomiting; R0002101:Supplement eTable 8
A4	events	0 / 38	not stated; safety; diarrhea; R0002101:Supplement eTable 8
A4	events	0 / 38	not stated; safety; vomiting; R0002101:Supplement eTable 8
A5	events	0 / 39	not stated; safety; diarrhea; R0002101:Supplement eTable 8
A5	events	1 / 39	not stated; safety; vomiting; R0002101:Supplement eTable 8

Acute pancreatitis (5 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 39	not stated; safety; R0002101:Table 3
A2	events	0 / 39	not stated; safety; R0002101:Table 3
A3	events	0 / 39	not stated; safety; R0002101:Table 3
A4	events	0 / 38	not stated; safety; R0002101:Table 3
A5	events	0 / 39	not stated; safety; R0002101:Table 3