parallel randomized trial

SURMOUNT-4

Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo for Maintenance of Weight Loss in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-4)

Weight maintenance after a GLP-1 receptor agonist containing run in NCT04660643S000242

Design

Randomized: 670
Start year: 2021
Treatment: 52 weeks, follow-up 56 weeks
Countries: Argentina, Brazil, Taiwan, United States (70 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 18 or more; BMI 30 or more, or 27 or more with weight related complication; no diabetes; MTD 10 or 15 mg reached by week 36

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: not reported
Primary estimand: treatment policy
Analysis population: full analysis
Missing data: multiple imputation, retrieved dropouts (hybrid)

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg Tirzepatide MTD (10 or 15 mg) continued	lifestyle: standard	335	335	300
A2	Placebo Placebo (switched from tirzepatide MTD)	lifestyle: standard	335	335	275

Baseline characteristics

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

Characteristic	Statistic	Tirzepatide subcutaneous once weekly, maximum tolerated dose: 10 or 15 mg A1	Placebo A2
age: 65 or older	n	39	33
age: 65 or older	percent	11.6	9.9
age: less than 65	n	296	302
age: less than 65	percent	88.4	90.1
age	mean (years)	49.2	48.1
age	sd (years)	12.8	12.4
asian	n	26	22
asian	percent	7.8	6.6
black	n	39	36
black	percent	11.6	10.7
bmi: 25 to less than 30	n	122	120
bmi: 25 to less than 30	percent	36.4	35.8
bmi: 30 to less than 35	n	88	75
bmi: 30 to less than 35	percent	26.3	22.4
bmi: 35 to less than 40	n	41	43
bmi: 35 to less than 40	percent	12.2	12.8
bmi: 40 or more	n	25	34
bmi: 40 or more	percent	7.5	10.1
bmi: less than 25	n	59	63
bmi: less than 25	percent	17.6	18.8
bmi	mean (kg/m2)	30.3	30.7
bmi	sd (kg/m2)	6.0	6.8
egfr: 30 to less than 45	n	2	1
egfr: 30 to less than 45	percent	0.6	0.3
egfr: 45 to less than 60	n	7	7
egfr: 45 to less than 60	percent	2.1	2.1
egfr: 60 to less than 90	n	108	89
egfr: 60 to less than 90	percent	32.2	26.6
egfr: 90 or more	n	218	238
egfr: 90 or more	percent	65.1	71.0
egfr	mean (mL/min/1.73 m2)	96.4	97.9
egfr	sd (mL/min/1.73 m2)	18.8	17.9
established cvd	n	18	23
established cvd	percent	5.4	6.9
female	n	236	237
female	percent	70.4	70.7
hba1c	mean (percent)	5.07	5.04
hba1c	sd (percent)	0.30	0.31
hispanic	n	141	155
hispanic	percent	42.1	46.3
other race american indian alaska native	n	0	0
other race multiple	n	5	3
other race multiple	percent	1.5	0.9
other race native hawaiian pacific islander	n	1	1
other race native hawaiian pacific islander	percent	0.3	0.3
sbp	mean (mmHg)	115	115
sbp	sd (mmHg)	13	12
waist	mean (cm)	96.8	98.2
waist	sd (cm)	14.1	16.0
weight	mean (kg)	84.6	85.8
weight	sd (kg)	19.8	22.3
white	n	264	273
white	percent	78.8	81.5

Results

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

Percent body weight change after randomization in maintenance trials (19 lines; O12)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
28	A1	percent change	-6.0 percent	-6.7 to -5.3	332	hypothetical; modified itt; R0018941:Supplement eTable 3
28	A1 vs A2	md	-15.9 percent	-17.0 to -14.9		hypothetical; modified itt; registry:outcomes
28	A1 vs A2	md	-15.9 percent	-16.9 to -14.9		hypothetical; modified itt; R0018941:Supplement eTable 3
28	A1	percent change	-5.4 percent	-6.3 to -4.6	335	treatment policy; full analysis; R0018941:Table 2
28	A1 vs A2	md	-15.4 percent	-16.8 to -14.1		treatment policy; full analysis; R0018941:Table 2
28	A2	percent change	10.0 percent	9.0 to 11.0	335	treatment policy; full analysis; R0018941:Table 2
28	A2	percent change	9.9 percent	9.2 to 10.6	329	hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1	percent change	-7.0 percent		37	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A1	percent change	-6.7 percent	-7.7 to -5.7	332	hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1 vs A2	md	-21.4 percent	-22.9 to -20.0		hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1	percent change	-5.5 percent	-6.8 to -4.2	335	treatment policy; full analysis; R0018941:Table 2
52	A1 vs A2	md	-19.4 percent	-21.2 to -17.7		treatment policy; full analysis; R0018941:Table 2
52	A1 vs A2	md	-20.1 percent	-23.4 to -16.8		hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A1	percent change	-6.6 percent		295	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A1 vs A2	md	-21.6 percent	-23.2 to -20.0		hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
52	A2	percent change	13.1 percent		29	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
52	A2	percent change	14.8 percent	13.8 to 15.8	329	hypothetical; modified itt; R0018941:Supplement eTable 3
52	A2	percent change	14.0 percent	12.8 to 15.2	335	treatment policy; full analysis; R0018941:Table 2
52	A2	percent change	15.0 percent		300	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 335	treatment policy; safety; R0018941:Table 3
	A2	events				0 / 335	treatment policy; safety; R0018941:Table 3

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	0.4 points		303	hypothetical; modified itt; R0015011:Figure 1B
52	A1	final	54.9 points			hypothetical; other; R0017931:Abstract
52	A1 vs A2	md	1.8 points	1.0 to 2.6		hypothetical; modified itt; R0015011:Figure 1B
52	A2	final	53.1 points			hypothetical; other; R0017931:Abstract
52	A2	change	-1.4 points		276	hypothetical; modified itt; R0015011:Figure 1B

Physical functioning (any instrument) (20 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A2	md	9.4 points		6.8 to 12.0		hypothetical; modified itt; registry:outcomes
52	A1	change	4.3 points			301	hypothetical; modified itt; R0015011:Figure 3B
52	A1	change	4.3 points		2.5 to 6.1		hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1	change	4.4 points	0.91		293	hypothetical; modified itt; registry:outcomes
52	A1	change	0.8 points			303	hypothetical; modified itt; R0015011:Figure 1B
52	A1	change	0.8 points		0.2 to 1.4	295	hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1	final	85.7 points				hypothetical; other; R0017931:Abstract
52	A1	final	54.2 points				hypothetical; other; R0017931:Abstract
52	A1 vs A2	md	9.4 points		6.9 to 12.0		hypothetical; modified itt; R0015011:Figure 3B
52	A1 vs A2	md	9.4 points		6.9 to 12.0		hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1 vs A2	md	2.6 points		1.8 to 3.5		hypothetical; modified itt; R0015011:Figure 1B
52	A1 vs A2	md	2.6 points		1.8 to 3.5		hypothetical; modified itt; R0018941:Supplement eTable 3
52	A1 vs A2	md	2.6 points		1.7 to 3.5		hypothetical; modified itt; registry:outcomes
52	A2	change	-5.1 points			278	hypothetical; modified itt; R0015011:Figure 3B
52	A2	change	-5.1 points		-6.9 to -3.3		hypothetical; modified itt; R0018941:Supplement eTable 3
52	A2	change	-5.0 points	0.95		272	hypothetical; modified itt; registry:outcomes
52	A2	change	-1.8 points			276	hypothetical; modified itt; R0015011:Figure 1B
52	A2	change	-1.8 points		-2.4 to -1.2	270	hypothetical; modified itt; R0018941:Supplement eTable 3
52	A2	final	76.2 points				hypothetical; other; R0017931:Abstract
52	A2	final	51.6 points				hypothetical; other; R0017931:Abstract

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	0.003 points		299	hypothetical; modified itt; R0015011:Figure 5A
52	A1	change	4.7 points		301	hypothetical; modified itt; R0015011:Figure 3B
52	A1	final	86.4 points			hypothetical; other; R0017931:Abstract
52	A1 vs A2	md	0.032 points	0.008 to 0.057		hypothetical; modified itt; R0015011:Figure 5A
52	A1 vs A2	md	11.1 points	8.9 to 13.3		hypothetical; modified itt; R0015011:Figure 3B
52	A2	change	-0.029 points		275	hypothetical; modified itt; R0015011:Figure 5A
52	A2	change	-6.4 points		278	hypothetical; modified itt; R0015011:Figure 3B
52	A2	final	75.3 points			hypothetical; other; R0017931:Abstract

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				10 / 335	treatment policy; safety; R0018941:Table 3
	A2	events				10 / 335	treatment policy; safety; R0018941:Table 3

Discontinuation due to adverse events (20 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	1 / 335	treatment policy; safety; cardiac failure congestive; R0018941:Table 3
A1	events	6 / 335	treatment policy; safety; R0018941:Table 3
A1	events	1 / 335	treatment policy; safety; abdominal pain; R0018941:Table 3
A1	events	0 / 335	treatment policy; safety; adenocarcinoma of colon; R0018941:Table 3
A1	events	0 / 335	treatment policy; safety; colorectal cancer; R0018941:Table 3
A1	events	2 / 335	treatment policy; safety; diarrhea; R0018941:Table 3
A1	events	0 / 335	treatment policy; safety; non-hodgkin lymphoma; R0018941:Table 3
A1	events	1 / 335	treatment policy; safety; pancreatic enzymes increased; R0018941:Table 3
A1	events	1 / 335	treatment policy; safety; vomiting; R0018941:Table 3
A1	events	0 / 335	not stated; randomized; R0018941:Figure 1
A2	events	1 / 335	treatment policy; safety; adenocarcinoma of colon; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; cardiac failure congestive; R0018941:Table 3
A2	events	1 / 335	treatment policy; safety; colorectal cancer; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; diarrhea; R0018941:Table 3
A2	events	1 / 335	treatment policy; safety; non-hodgkin lymphoma; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; pancreatic enzymes increased; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; vomiting; R0018941:Table 3
A2	events	3 / 335	treatment policy; safety; R0018941:Table 3
A2	events	0 / 335	not stated; randomized; R0018941:Figure 1
A2	events	0 / 335	treatment policy; safety; abdominal pain; R0018941:Table 3

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	27 / 335	treatment policy; safety; R0018941:Table 3
A1	events	1 / 335	not stated; safety; registry:adverse_events
A2	events	9 / 335	treatment policy; safety; R0018941:Table 3
A2	events	0 / 335	not stated; safety; registry:adverse_events

Vomiting (5 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	18 / 335	not stated; safety; registry:adverse_events
A1	events	1 / 335	not stated; safety; registry:adverse_events
A1	events	19 / 335	treatment policy; safety; R0018941:Table 3
A2	events	4 / 335	treatment policy; safety; R0018941:Table 3
A2	events	0 / 335	not stated; safety; registry:adverse_events

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				36 / 335	treatment policy; safety; R0018941:Table 3
	A2	events				16 / 335	treatment policy; safety; R0018941:Table 3

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				12 / 335	not stated; safety; registry:adverse_events
	A2	events				8 / 335	not stated; safety; registry:adverse_events

Discontinuation due to gastrointestinal adverse events (8 lines; O27E)

Arm	Statistic	Events / N	Detail
A1	events	1 / 335	treatment policy; safety; vomiting; R0018941:Table 3
A1	events	1 / 335	treatment policy; safety; abdominal pain; R0018941:Table 3
A1	events	2 / 335	treatment policy; safety; diarrhea; R0018941:Table 3
A1	events	0 / 335	not stated; randomized; R0018941:Figure 1
A2	events	0 / 335	treatment policy; safety; abdominal pain; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; diarrhea; R0018941:Table 3
A2	events	0 / 335	treatment policy; safety; vomiting; R0018941:Table 3
A2	events	0 / 335	not stated; randomized; R0018941:Figure 1

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 335	not stated; safety; cholelithiasis; registry:adverse_events
A1	events	0 / 335	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	1 / 335	treatment policy; safety; cholelithiasis; R0018941:Table 3
A1	events	0 / 335	treatment policy; safety; acute cholecystitis; R0018941:Table 3
A2	events	0 / 335	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	3 / 335	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	3 / 335	treatment policy; safety; acute cholecystitis; R0018941:Table 3
A2	events	1 / 335	treatment policy; safety; cholelithiasis; R0018941:Table 3

Acute pancreatitis (2 lines; O29)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 335	treatment policy; safety; pancreatitis; R0018941:Table 3
	A2	events				0 / 335	treatment policy; safety; pancreatitis; R0018941:Table 3

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 335	treatment policy; safety; R0018941:Results
	A2	events				0 / 335	treatment policy; safety; R0018941:Results

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 335	treatment policy; safety; R0018941:Table 3
	A2	events				0 / 335	treatment policy; safety; R0018941:Table 3

Intestinal obstruction or ileus (4 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	1 / 335	not stated; safety; intestinal obstruction; registry:adverse_events
A1	events	1 / 335	not stated; safety; small intestinal obstruction; registry:adverse_events
A2	events	1 / 335	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 335	not stated; safety; small intestinal obstruction; registry:adverse_events

Pancreatic cancer (2 lines; O38)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				0 / 335	treatment policy; safety; R0018941:Results
	A2	events				0 / 335	treatment policy; safety; R0018941:Results

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				3 / 335	treatment policy; safety; R0018941:Table 3
	A2	events				3 / 335	treatment policy; safety; R0018941:Table 3