parallel randomized trial

SOUL

Semaglutide Cardiovascular Outcomes Trial in Patients With Type 2 Diabetes

Type 2 diabetes (adults)NCT03914326S002179

Design

Randomized: 9,650
Start year: 2019
Treatment: 260.9 weeks, follow-up 265 weeks
Countries: multinational (444 sites)
Sponsor: Novo Nordisk A/S (industry)
Eligibility: age 50 or more; T2D with HbA1c 6.5 to 10 percent; ASCVD and/or CKD with eGFR below 60

Conduct and analysis

Blinding: double blind
Sequence generation: other adequate
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: censoring at end of in-trial period

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Semaglutide 14 mg oral once daily (original tablet) Oral semaglutide	standard of care for diabetes and cardiovascular risk; no added GLP-1 RA; lifestyle: standard	4,825	4,825
A2	Placebo Placebo	standard of care for diabetes and cardiovascular risk; no added GLP-1 RA; lifestyle: standard	4,825	4,825

Baseline characteristics

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

Characteristic	Statistic	Semaglutide 14 mg oral once daily (original tablet) A1	Placebo A2
age	mean (years)	66.1	66.1
age	median (years)	66	66
age	q1 (years)	61	61
age	q3 (years)	72	72
age	sd (years)	7.6	7.5
asian	n	1134	1121
asian	percent	23.5	23.2
black	n	124	128
black	percent	2.6	2.7
bmi	median (kg/m2)	30.3	30.4
bmi	q1 (kg/m2)	26.9	27.0
bmi	q3 (kg/m2)	34.2	34.5
diabetes duration	median (years)	14.7	14.6
diabetes duration	q1 (years)	9.0	8.9
diabetes duration	q3 (years)	20.8	20.8
egfr: 15 to less than 30	n	113	114
egfr: 15 to less than 30	percent	2.3	2.4
egfr: 30 to less than 45	n	474	475
egfr: 30 to less than 45	percent	9.8	9.8
egfr: 45 to less than 60	n	811	818
egfr: 45 to less than 60	percent	16.8	17.0
egfr: 60 to less than 90	n	1845	1903
egfr: 60 to less than 90	percent	38.2	39.4
egfr: 90 or more	n	1531	1472
egfr: 90 or more	percent	31.7	30.5
egfr: less than 15	n	7	4
egfr: less than 15	percent	0.1
egfr	median (mL/min/1.73 m2)	77.0	76.0
egfr	q1 (mL/min/1.73 m2)	56.0	56.0
egfr	q3 (mL/min/1.73 m2)	93.0	92.0
established cvd	n	4033	4055
female	n	1376	1414
female	percent	28.5	29.3
hba1c	median (percent)	7.8	7.8
hba1c	q1 (percent)	7.1	7.1
hba1c	q3 (percent)	8.7	8.6
hispanic	n	674	706
hispanic	percent	14.0	14.6
insulin use	n	2476	2413
insulin use	percent	51.3	50.0
metformin use	n	3651	3675
metformin use	percent	75.7	76.2
other ckd	n	2041	2051
other ckd	percent	42.3	42.5
other heart failure	n	1105	1124
other heart failure	percent	22.9	23.3
other race american indian alaska native	n	7	12
other race american indian alaska native	percent	0.1	0.2
other race native hawaiian pacific islander	n	4	5
other race native hawaiian pacific islander	percent		0.1
other race other	n	185	192
other race other	percent	3.8	4.0
sbp	median (mmHg)	134	135
sbp	q1 (mmHg)	124	124
sbp	q3 (mmHg)	144	144
sglt2i use	n	1296	1300
sglt2i use	percent	26.9	26.9
weight	median (kg)	85.7	86.3
weight	q1 (kg)	74.0	74.4
weight	q3 (kg)	98.9	100.0
white	n	3327	3321
white	percent	69.0	68.8

Results

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

HbA1c change (12 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-0.77 percent			4311	treatment policy; full analysis; R0014491:Supplement eFigure 5A
52	A2	change	-0.06 percent			4292	treatment policy; full analysis; R0014491:Supplement eFigure 5A
104	A1	change	-0.71 percent	1.22		4076	treatment policy; full analysis; registry:outcomes
104	A1	change	-0.73 percent		-0.77 to -0.69	3529	treatment policy; full analysis; background:no_sglt2i; R0006143:Table 2
104	A1 vs A2	md	-0.57 percent		-0.63 to -0.52		treatment policy; full analysis; background:no_sglt2i; R0006143:Table 2
104	A1	change	-0.66 percent		-0.73 to -0.60	1296	treatment policy; full analysis; background:sglt2i; R0006143:Table 2
104	A1 vs A2	md	-0.53 percent		-0.62 to -0.45		treatment policy; full analysis; background:sglt2i; R0006143:Table 2
104	A2	change	-0.13 percent		-0.20 to -0.067	1300	treatment policy; full analysis; background:sglt2i; R0006143:Table 2
104	A2	change	-0.15 percent	1.19		4004	treatment policy; full analysis; registry:outcomes
104	A2	change	-0.16 percent		-0.20 to -0.12	3525	treatment policy; full analysis; background:no_sglt2i; R0006143:Table 2
208	A1	change	-0.54 percent			2143	treatment policy; full analysis; R0014491:Supplement eFigure 5A
208	A2	change	0.01 percent			2044	treatment policy; full analysis; R0014491:Supplement eFigure 5A

Body weight change in kilograms (diabetes) (2 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
104	A1	change	-4.21 kg	5.85		4251	treatment policy; full analysis; registry:outcomes
104	A2	change	-1.28 kg	4.90		4155	treatment policy; full analysis; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				76 / 4825	treatment policy; full analysis; registry:outcomes
	A2	events				84 / 4825	treatment policy; full analysis; registry:outcomes

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	rate				4825	treatment policy; full analysis; registry:outcomes
	A2	rate				4825	treatment policy; full analysis; registry:outcomes

Systolic blood pressure change (6 lines; O05)

Week	Arm	Statistic	Estimate	Events / N	Detail
52	A1	change	-3.06 mmHg	4386	treatment policy; full analysis; R0014491:Supplement eFigure 2A
52	A2	change	-1.08 mmHg	4361	treatment policy; full analysis; R0014491:Supplement eFigure 2A
104	A1	change	-2.98 mmHg	4264	treatment policy; full analysis; R0014491:Supplement eFigure 2A
104	A2	change	-1.33 mmHg	4169	treatment policy; full analysis; R0014491:Supplement eFigure 2A
208	A1	change	-3.47 mmHg	2189	treatment policy; full analysis; R0014491:Supplement eFigure 2A
208	A2	change	-2.37 mmHg	2104	treatment policy; full analysis; R0014491:Supplement eFigure 2A

Percent body weight change (10 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	percent change	-4.13 percent		4367	treatment policy; full analysis; R0014491:Supplement eFigure 5C
52	A2	percent change	-0.57 percent		4346	treatment policy; full analysis; R0014491:Supplement eFigure 5C
104	A1	percent change	-4.74 percent		4251	treatment policy; full analysis; R0014491:Supplement eFigure 5C
104	A2	percent change	-1.32 percent		4155	treatment policy; full analysis; R0014491:Supplement eFigure 5C
156	A1 vs A2	md	-3.26 percent	-3.55 to -2.98		treatment policy; full analysis; R0014491:Results
156	A1	percent change	-5.25 percent		4019	treatment policy; full analysis; R0014491:Supplement eFigure 5C
156	A1	percent change	-5.26 percent		4825	treatment policy; full analysis; R0014491:Results
156	A2	percent change	-1.98 percent		3894	treatment policy; full analysis; R0014491:Supplement eFigure 5C
208	A1	percent change	-5.84 percent		2182	treatment policy; full analysis; R0014491:Supplement eFigure 5C
208	A2	percent change	-2.47 percent		2098	treatment policy; full analysis; R0014491:Supplement eFigure 5C

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				123 / 4825	not stated; safety; registry:adverse_events
	A2	events				151 / 4825	not stated; safety; registry:adverse_events

All cause mortality (17 lines; O20)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.91	0.80 to 1.02		treatment policy; full analysis; R0006143:Figure 2
A1	events			528 / 4825	not stated; safety; registry:adverse_events
A1	events			528 / 4825	treatment policy; full analysis; R0006143:Figure 2
A1	events			115 / 1296	treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A1 vs A2	hr	0.91	0.70 to 1.17		treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A1	events			251 / 1935	treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3
A1 vs A2	hr	0.86	0.73 to 1.02		treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3
A1	events			460 / 4033	treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3
A1 vs A2	hr	0.93	0.82 to 1.05		treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3
A1	events			413 / 3529	treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A1 vs A2	hr	0.91	0.79 to 1.03		treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A2	events			579 / 4825	not stated; safety; registry:adverse_events
A2	events			577 / 4825	treatment policy; full analysis; R0006143:Figure 2
A2	events			495 / 4055	treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3
A2	events			126 / 1300	treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A2	events			451 / 3525	treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A2	events			284 / 1926	treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3

Three point MACE (15 lines; O21)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.86	0.77 to 0.96		treatment policy; full analysis; R0006143:Figure 2
A1	events			579 / 4825	treatment policy; full analysis; R0006143:Figure 2
A1	events			436 / 3529	treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A1 vs A2	hr	0.84	0.74 to 0.95		treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A1	events			143 / 1296	treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A1 vs A2	hr	0.89	0.71 to 1.11		treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A1	events			252 / 1935	treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3
A1 vs A2	hr	0.80	0.67 to 0.94		treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3
A1	events			528 / 4033	treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3
A1 vs A2	hr	0.89	0.79 to 1.00		treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3
A2	events			304 / 1926	treatment policy; full analysis; egfr:less_than_60; R0006143:Figure 3
A2	events			158 / 1300	treatment policy; full analysis; background:sglt2i; R0006143:Figure 2
A2	events			668 / 4825	treatment policy; full analysis; R0006143:Figure 2
A2	events			510 / 3525	treatment policy; full analysis; background:no_sglt2i; R0006143:Figure 2
A2	events			588 / 4055	treatment policy; full analysis; established_cvd:yes; R0006143:Figure 3

Four point MACE including unstable angina (2 lines; O21B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				670 / 4825	treatment policy; full analysis; registry:outcomes
	A2	events				777 / 4825	treatment policy; full analysis; registry:outcomes

Kidney composite outcome (12 lines; O22)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1 vs A2	hr	0.82	0.63 to 1.08		treatment policy; full analysis; background:no_sglt2i; R0015783:Results
A1	events			112 / 4825	treatment policy; full analysis; R0015783:Table 1
A1 vs A2	hr	0.86	0.66 to 1.10		treatment policy; full analysis; R0015783:Table 1
A1	events			98 / 3529	treatment policy; full analysis; background:no_sglt2i; R0015783:Results
A1	events			14 / 1296	treatment policy; full analysis; background:sglt2i; R0015783:Results
A1 vs A2	hr	1.15	0.53 to 2.53		treatment policy; full analysis; background:sglt2i; R0015783:Results
A1	events			72 / 1405	treatment policy; full analysis; egfr:less_than_60; R0015783:Results
A1 vs A2	hr	0.80	0.58 to 1.09		treatment policy; full analysis; egfr:less_than_60; R0015783:Results
A2	events			12 / 1300	treatment policy; full analysis; background:sglt2i; R0015783:Results
A2	events			87 / 1411	treatment policy; full analysis; egfr:less_than_60; R0015783:Results
A2	events			129 / 4825	treatment policy; full analysis; R0015783:Table 1
A2	events			117 / 3525	treatment policy; full analysis; background:no_sglt2i; R0015783:Results

Kidney composite including cardiovascular death (3 lines; O22D)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			403 / 4825	treatment policy; full analysis; R0015783:Table 1
A1 vs A2	hr	0.91	0.80 to 1.05		treatment policy; full analysis; R0015783:Table 1
A2	events			435 / 4825	treatment policy; full analysis; R0015783:Table 1

Heart failure events (2 lines; O23B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				146 / 4825	treatment policy; full analysis; registry:outcomes
	A2	events				167 / 4825	treatment policy; full analysis; registry:outcomes

Serious adverse events (6 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	2312 / 4825	not stated; safety; R0015783:Results
A1	events	173 / 296	treatment policy; full analysis; hf:hfref; R0014773:Table 2
A1	events	227 / 494	treatment policy; full analysis; hf:hfpef; R0014773:Table 2
A2	events	2427 / 4825	not stated; safety; R0015783:Results
A2	events	261 / 497	treatment policy; full analysis; hf:hfpef; R0014773:Table 2
A2	events	187 / 296	treatment policy; full analysis; hf:hfref; R0014773:Table 2

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	61 / 494	treatment policy; full analysis; hf:hfpef; R0014773:Table 2
A1	events	58 / 296	treatment policy; full analysis; hf:hfref; R0014773:Table 2
A2	events	51 / 497	treatment policy; full analysis; hf:hfpef; R0014773:Table 2
A2	events	52 / 296	treatment policy; full analysis; hf:hfref; R0014773:Table 2

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	4 / 4825	not stated; safety; registry:adverse_events
A1	events	344 / 4825	not stated; safety; registry:adverse_events
A2	events	3 / 4825	not stated; safety; registry:adverse_events
A2	events	62 / 4825	not stated; safety; registry:adverse_events

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				13 / 4825	not stated; safety; registry:adverse_events
	A2	events				7 / 4825	not stated; safety; registry:adverse_events

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	1 / 4825	not stated; safety; diarrhoea haemorrhagic; registry:adverse_events
A1	events	12 / 4825	not stated; safety; diarrhoea; registry:adverse_events
A2	events	0 / 4825	not stated; safety; diarrhoea haemorrhagic; registry:adverse_events
A2	events	10 / 4825	not stated; safety; diarrhoea; registry:adverse_events

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				8 / 4825	not stated; safety; registry:adverse_events
	A2	events				7 / 4825	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (36 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 4825	not stated; safety; biliary obstruction; registry:adverse_events
A1	events	1 / 4825	not stated; safety; bile duct stenosis; registry:adverse_events
A1	events	2 / 4825	not stated; safety; cholangitis acute; registry:adverse_events
A1	events	0 / 4825	not stated; safety; cholangitis chronic; registry:adverse_events
A1	events	6 / 4825	not stated; safety; cholangitis; registry:adverse_events
A1	events	0 / 4825	not stated; safety; gallbladder abscess; registry:adverse_events
A1	events	1 / 4825	not stated; safety; gallbladder disorder; registry:adverse_events
A1	events	4 / 4825	not stated; safety; gallbladder empyema; registry:adverse_events
A1	events	0 / 4825	not stated; safety; gallbladder oedema; registry:adverse_events
A1	events	0 / 4825	not stated; safety; gallbladder rupture; registry:adverse_events
A1	events	0 / 4825	not stated; safety; hydrocholecystis; registry:adverse_events
A1	events	1 / 4825	not stated; safety; porcelain gallbladder; registry:adverse_events
A1	events	1 / 4825	not stated; safety; acute cholecystitis necrotic; registry:adverse_events
A1	events	31 / 4825	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	5 / 4825	not stated; safety; cholecystitis chronic; registry:adverse_events
A1	events	17 / 4825	not stated; safety; cholecystitis; registry:adverse_events
A1	events	8 / 4825	not stated; safety; bile duct stone; registry:adverse_events
A1	events	29 / 4825	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	1 / 4825	not stated; safety; gallbladder empyema; registry:adverse_events
A2	events	1 / 4825	not stated; safety; gallbladder oedema; registry:adverse_events
A2	events	3 / 4825	not stated; safety; gallbladder rupture; registry:adverse_events
A2	events	0 / 4825	not stated; safety; gallbladder disorder; registry:adverse_events
A2	events	2 / 4825	not stated; safety; hydrocholecystis; registry:adverse_events
A2	events	0 / 4825	not stated; safety; porcelain gallbladder; registry:adverse_events
A2	events	1 / 4825	not stated; safety; gallbladder abscess; registry:adverse_events
A2	events	9 / 4825	not stated; safety; cholangitis; registry:adverse_events
A2	events	1 / 4825	not stated; safety; cholangitis chronic; registry:adverse_events
A2	events	3 / 4825	not stated; safety; cholangitis acute; registry:adverse_events
A2	events	3 / 4825	not stated; safety; acute cholecystitis necrotic; registry:adverse_events
A2	events	19 / 4825	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	6 / 4825	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	12 / 4825	not stated; safety; cholecystitis; registry:adverse_events
A2	events	1 / 4825	not stated; safety; biliary obstruction; registry:adverse_events
A2	events	0 / 4825	not stated; safety; bile duct stenosis; registry:adverse_events
A2	events	6 / 4825	not stated; safety; bile duct stone; registry:adverse_events
A2	events	30 / 4825	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (10 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	1 / 4825	not stated; safety; alcoholic pancreatitis; registry:adverse_events
A1	events	5 / 4825	not stated; safety; obstructive pancreatitis; registry:adverse_events
A1	events	1 / 4825	not stated; safety; oedematous pancreatitis; registry:adverse_events
A1	events	16 / 4825	not stated; safety; pancreatitis acute; registry:adverse_events
A1	events	2 / 4825	not stated; safety; pancreatitis; registry:adverse_events
A2	events	0 / 4825	not stated; safety; alcoholic pancreatitis; registry:adverse_events
A2	events	5 / 4825	not stated; safety; obstructive pancreatitis; registry:adverse_events
A2	events	0 / 4825	not stated; safety; oedematous pancreatitis; registry:adverse_events
A2	events	14 / 4825	not stated; safety; pancreatitis acute; registry:adverse_events
A2	events	1 / 4825	not stated; safety; pancreatitis; registry:adverse_events

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 4825	not stated; safety; registry:adverse_events
	A2	events				0 / 4825	not stated; safety; registry:adverse_events

Thyroid cancer (any) (6 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 4825	not stated; safety; medullary thyroid cancer; registry:adverse_events
A1	events	5 / 4825	not stated; safety; papillary thyroid cancer; registry:adverse_events
A1	events	0 / 4825	not stated; safety; thyroid cancer metastatic; registry:adverse_events
A2	events	0 / 4825	not stated; safety; medullary thyroid cancer; registry:adverse_events
A2	events	1 / 4825	not stated; safety; papillary thyroid cancer; registry:adverse_events
A2	events	1 / 4825	not stated; safety; thyroid cancer metastatic; registry:adverse_events

Diabetic retinopathy complications (14 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	1 / 4825	not stated; safety; blindness unilateral; registry:adverse_events
A1	events	1 / 4825	not stated; safety; blindness; registry:adverse_events
A1	events	1 / 4825	not stated; safety; diabetic retinal oedema; registry:adverse_events
A1	events	943 / 4825	not stated; safety; diabetic retinopathy; registry:adverse_events
A1	events	29 / 4825	not stated; safety; diabetic retinopathy; registry:adverse_events
A1	events	0 / 4825	not stated; safety; retinopathy proliferative; registry:adverse_events
A1	events	11 / 4825	not stated; safety; vitreous haemorrhage; registry:adverse_events
A2	events	932 / 4825	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	0 / 4825	not stated; safety; blindness unilateral; registry:adverse_events
A2	events	1 / 4825	not stated; safety; blindness; registry:adverse_events
A2	events	1 / 4825	not stated; safety; diabetic retinal oedema; registry:adverse_events
A2	events	15 / 4825	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	3 / 4825	not stated; safety; retinopathy proliferative; registry:adverse_events
A2	events	9 / 4825	not stated; safety; vitreous haemorrhage; registry:adverse_events

Suicidal ideation or behavior (4 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 4825	not stated; safety; suicidal ideation; registry:adverse_events
A1	events	2 / 4825	not stated; safety; suicide attempt; registry:adverse_events
A2	events	1 / 4825	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	2 / 4825	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 4825	not stated; safety; registry:adverse_events
	A2	events				1 / 4825	not stated; safety; registry:adverse_events

Gastroparesis (4 lines; O37A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 4825	not stated; safety; diabetic gastroparesis; registry:adverse_events
A1	events	3 / 4825	not stated; safety; impaired gastric emptying; registry:adverse_events
A2	events	1 / 4825	not stated; safety; diabetic gastroparesis; registry:adverse_events
A2	events	0 / 4825	not stated; safety; impaired gastric emptying; registry:adverse_events

Intestinal obstruction or ileus (12 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	2 / 4825	not stated; safety; ileus paralytic; registry:adverse_events
A1	events	6 / 4825	not stated; safety; ileus; registry:adverse_events
A1	events	5 / 4825	not stated; safety; intestinal obstruction; registry:adverse_events
A1	events	1 / 4825	not stated; safety; large intestinal obstruction; registry:adverse_events
A1	events	0 / 4825	not stated; safety; mechanical ileus; registry:adverse_events
A1	events	5 / 4825	not stated; safety; small intestinal obstruction; registry:adverse_events
A2	events	0 / 4825	not stated; safety; ileus paralytic; registry:adverse_events
A2	events	1 / 4825	not stated; safety; ileus; registry:adverse_events
A2	events	5 / 4825	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 4825	not stated; safety; large intestinal obstruction; registry:adverse_events
A2	events	1 / 4825	not stated; safety; mechanical ileus; registry:adverse_events
A2	events	6 / 4825	not stated; safety; small intestinal obstruction; registry:adverse_events

Pancreatic cancer (12 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	2 / 4825	not stated; safety; ductal adenocarcinoma of pancreas; registry:adverse_events
A1	events	6 / 4825	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A1	events	0 / 4825	not stated; safety; pancreatic carcinoma stage iv; registry:adverse_events
A1	events	6 / 4825	not stated; safety; pancreatic carcinoma; registry:adverse_events
A1	events	5 / 4825	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A1	events	0 / 4825	not stated; safety; pancreatic neuroendocrine tumour metastatic; registry:adverse_events
A2	events	4 / 4825	not stated; safety; pancreatic carcinoma; registry:adverse_events
A2	events	2 / 4825	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A2	events	3 / 4825	not stated; safety; ductal adenocarcinoma of pancreas; registry:adverse_events
A2	events	2 / 4825	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	3 / 4825	not stated; safety; pancreatic carcinoma stage iv; registry:adverse_events
A2	events	1 / 4825	not stated; safety; pancreatic neuroendocrine tumour metastatic; registry:adverse_events

Cardiovascular death or heart failure events (6 lines; O40)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			40 / 494	treatment policy; full analysis; hf:hfpef; R0014773:Results
A1 vs A2	hr	0.59	0.39 to 0.86		treatment policy; full analysis; hf:hfpef; R0014773:Results
A1 vs A2	hr	0.98	0.70 to 1.38		treatment policy; full analysis; hf:hfref; R0014773:Results
A1	events			68 / 296	treatment policy; full analysis; hf:hfref; R0014773:Results
A2	events			67 / 296	treatment policy; full analysis; hf:hfref; R0014773:Results
A2	events			67 / 497	treatment policy; full analysis; hf:hfpef; R0014773:Results

eGFR total slope (3 lines; O51)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
260	A1 vs A2	md	0.40 mL/min/1.73 m2 per year	0.27 to 0.53		treatment policy; full analysis; R0015783:Results
260	A1	slope	-1.67 mL/min/1.73 m2 per year		4819	treatment policy; full analysis; R0015783:Results
260	A2	slope	-2.06 mL/min/1.73 m2 per year		4822	treatment policy; full analysis; R0015783:Results