parallel randomized trial

SURMOUNT-3

Efficacy and Safety of Tirzepatide Once Weekly Versus Placebo After an Intensive Lifestyle Program in Participants Without Type 2 Diabetes Who Have Obesity or Are Overweight With Weight-Related Comorbidities: A Randomized, Double Blind, Placebo-Controlled Trial (SURMOUNT-3)

Overweight or obesity without diabetes (adults)NCT04657016S002157

Design

Randomized: 579
Start year: 2021
Treatment: 72 weeks, follow-up 76 weeks
Countries: Argentina, Brazil, United States (62 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 18 or older; BMI 30 or more, or 27 or more with comorbidity; no diabetes; at least 5 percent loss in lead in

Conduct and analysis

Blinding: double blind
Sequence generation: computer
Allocation concealment: central
Outcome adjudication: yes
Primary estimand: treatment policy
Analysis population: modified itt
Missing data: hybrid retrieved dropout imputation

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)	lifestyle: standard	287	287	226
A2	Placebo Placebo	lifestyle: standard	292	292	203

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	mean (years)	45.4	45.7
age	sd (years)	12.6	11.8
asian	n	2	2
asian	percent	0.7	0.7
black	n	31	32
black	percent	10.8	11.0
bmi: 27 to less than 30	n	32	38
bmi: 27 to less than 30	percent	11.1	13.0
bmi: 30 to less than 35	n	100	107
bmi: 30 to less than 35	percent	34.8	36.6
bmi: 35 to less than 40	n	95	79
bmi: 35 to less than 40	percent	33.1	27.1
bmi: 40 or more	n	55	56
bmi: 40 or more	percent	19.2	19.2
bmi: less than 27	n	5	12
bmi: less than 27	percent	1.7	4.1
bmi	mean (kg/m2)	36.1	35.7
bmi	sd (kg/m2)	6.1	6.4
egfr	mean (mL/min/1.73 m2)	95.6	97.1
egfr	sd (mL/min/1.73 m2)	17.1	16.7
established cvd	n	5	6
established cvd	percent	1.7	2.1
female	n	181	183
female	percent	63.1	62.7
hba1c	mean (percent)	5.3	5.4
hba1c	sd (percent)	0.4	0.4
hispanic	n	151	161
hispanic	percent	52.6	55.1
other race american indian alaska native	n	2	4
other race american indian alaska native	percent	0.7	1.4
other race multiple	n	6	2
other race multiple	percent	2.1	0.7
other race native hawaiian pacific islander	n	0	0
sbp	mean (mmHg)	121.4	120.5
sbp	sd (mmHg)	12.7	12.4
waist	mean (cm)	109.3	109.6
waist	sd (cm)	15.2	15.1
weight	mean (kg)	102.5	101.3
weight	sd (kg)	22.1	20.7
white	n	246	252
white	percent	85.7	86.3

Analyses this trial contributes to

Results

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

Systolic blood pressure change (6 lines; O05)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1 vs A2	md	-9.2 mmHg		-11.2 to -7.2		hypothetical; modified itt; R0007405:Table 4
72	A1	change	-5.8 mmHg	0.73		284	hypothetical; modified itt; registry:outcomes
72	A1	change	-5.1 mmHg	0.7			hypothetical; modified itt; R0007405:Table 4
72	A1 vs A2	md	-10.2 mmHg		-12.2 to -8.1		hypothetical; modified itt; registry:outcomes
72	A2	change	4.1 mmHg	0.7			hypothetical; modified itt; R0007405:Table 4
72	A2	change	4.4 mmHg	0.76		291	hypothetical; modified itt; registry:outcomes

Percent body weight change (12 lines; O10)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1	percent change	-17.8 percent			20	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
72	A1	percent change	-21.1 percent	0.6		227	hypothetical; modified itt; R0007405:Results
72	A1 vs A2	md	-24.5 percent		-26.1 to -22.8		hypothetical; modified itt; R0007405:Results
72	A1	percent change	-18.4 percent	0.7		287	treatment policy; modified itt; R0007405:Table 4
72	A1 vs A2	md	-20.8 percent		-23.2 to -18.5		treatment policy; modified itt; R0007405:Table 4
72	A1 vs A2	md	-23.4 percent		-30.6 to -16.3		hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
72	A1	percent change	-21.4 percent			264	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
72	A1 vs A2	md	-24.5 percent		-26.2 to -22.8		hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
72	A2	percent change	5.6 percent			17	hypothetical; modified itt; age:65_or_older; R0013402:Figure 1
72	A2	percent change	3.2 percent			274	hypothetical; modified itt; age:less_than_65; R0013402:Figure 1
72	A2	percent change	3.3 percent	0.6		202	hypothetical; modified itt; R0007405:Results
72	A2	percent change	2.5 percent	1.0		292	treatment policy; modified itt; R0007405:Table 4

Weight loss of 5 percent or more (6 lines; O11A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1	responders	87.5	2.2		287	treatment policy; modified itt; R0007405:Table 4
72	A1 vs A2	or	34.6		19.2 to 62.6		treatment policy; modified itt; R0007405:Table 4
72	A1	responders	94.4			284	hypothetical; modified itt; R0007405:Results
72	A1 vs A2	or	130.4		70.0 to 242.8		hypothetical; modified itt; R0007405:Results
72	A2	responders	10.7			291	hypothetical; modified itt; R0007405:Results
72	A2	responders	16.5	3.0		292	treatment policy; modified itt; R0007405:Table 4

Weight loss of 10 percent or more (6 lines; O11B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1 vs A2	or	34.7		17.6 to 68.3		treatment policy; modified itt; R0007405:Table 4
72	A1	responders	88.0			284	hypothetical; modified itt; R0007405:Figure 2
72	A1 vs A2	or	153.95		78.90 to 300.37		hypothetical; modified itt; registry:outcomes
72	A1	responders	76.7	2.7		287	treatment policy; modified itt; R0007405:Table 4
72	A2	responders	4.8			291	hypothetical; modified itt; R0007405:Figure 2
72	A2	responders	8.9	2.4		292	treatment policy; modified itt; R0007405:Table 4

Weight loss of 15 percent or more (6 lines; O11C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1 vs A2	or	48.2		19.2 to 121.0		treatment policy; modified itt; R0007405:Table 4
72	A1	responders	73.9			284	hypothetical; modified itt; R0007405:Figure 2
72	A1 vs A2	or	144.48		62.65 to 333.21		hypothetical; modified itt; registry:outcomes
72	A1	responders	65.4	3.0		287	treatment policy; modified itt; R0007405:Table 4
72	A2	responders	4.2	1.8		292	treatment policy; modified itt; R0007405:Table 4
72	A2	responders	2.1			291	hypothetical; modified itt; R0007405:Figure 2

Weight loss of 20 percent or more (6 lines; O11D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1	responders	54.9			284	hypothetical; modified itt; R0007405:Figure 2
72	A1 vs A2	or	118.06		40.08 to 347.74		hypothetical; modified itt; registry:outcomes
72	A1	responders	44.7	3.0		287	treatment policy; modified itt; R0007405:Table 4
72	A1 vs A2	or	40.4		12.2 to 133.8		treatment policy; modified itt; R0007405:Table 4
72	A2	responders	1.0			291	hypothetical; modified itt; R0007405:Figure 2
72	A2	responders	2.2	1.3		292	treatment policy; modified itt; R0007405:Table 4

Weight loss of 25 percent or more (6 lines; O11E)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1	responders	36.3			284	hypothetical; modified itt; R0007405:Results
72	A1 vs A2	or	124.6		24.9 to 623.2		hypothetical; modified itt; R0007405:Results
72	A1	responders	28.7	2.7		287	treatment policy; modified itt; R0007405:Table 4
72	A1 vs A2	or	33.70		8.84 to 128.52		treatment policy; modified itt; R0007405:Table 4
72	A2	responders	1.2	0.9		292	treatment policy; modified itt; R0007405:Table 4
72	A2	responders	0.3			291	hypothetical; modified itt; R0007405:Results

Acute kidney injury (2 lines; O121)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 287	not stated; safety; registry:adverse_events
	A2	events				0 / 292	not stated; safety; registry:adverse_events

All cause mortality (2 lines; O20)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 287	not stated; safety; R0007405:Table 3
	A2	events				1 / 292	not stated; safety; R0007405:Table 3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 287	not stated; safety; R0007405:Table 3
	A2	events				1 / 292	not stated; safety; R0007405:Table 3

SF-36 physical component summary change (3 lines; O24A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1 vs A2	md	4.0 points		2.8 to 5.1		hypothetical; modified itt; R0016199:Table 1
72	A1	final	55.8 points	0.4		231	hypothetical; modified itt; R0016199:Table 1
72	A2	final	51.8 points	0.4		209	hypothetical; modified itt; R0016199:Table 1

Physical functioning (any instrument) (9 lines; O24B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
72	A1	change	3.3 points	0.4		231	hypothetical; modified itt; R0007405:Table 4
72	A1	change	13.9 points	1.1		226	hypothetical; modified itt; R0007405:Table 4
72	A1	final	55.0 points	0.4		231	hypothetical; modified itt; R0016199:Table 1
72	A1 vs A2	md	12.8 points		9.7 to 16.0		hypothetical; modified itt; R0007405:Table 4
72	A1 vs A2	md	3.9 points		2.8 to 4.9		hypothetical; modified itt; R0007405:Table 4
72	A1 vs A2	md	3.8 points		2.8 to 4.9		hypothetical; modified itt; R0016199:Table 1
72	A2	change	-0.6 points	0.4		209	hypothetical; modified itt; R0007405:Table 4
72	A2	final	51.1 points	0.4		209	hypothetical; modified itt; R0016199:Table 1
72	A2	change	1.1 points	1.2		201	hypothetical; modified itt; R0007405:Table 4

Health related quality of life total score (any instrument) (3 lines; O24C)

Week	Arm	Statistic	Estimate	95% CI	Detail
72	A1	change	0.03 points		hypothetical; modified itt; R0016199:Results
72	A1 vs A2	md	15.2 points	12.5 to 17.9	hypothetical; modified itt; R0016199:Figure 1
72	A2	change	-0.02 points		hypothetical; modified itt; R0016199:Results

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				17 / 287	not stated; safety; R0007405:Table 3
	A2	events				14 / 292	not stated; safety; R0007405:Table 3

Discontinuation due to adverse events (4 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	30 / 287	not stated; safety; R0007405:Table 3
A1	events	4 / 287	not stated; randomized; R0007405:Figure 1
A2	events	6 / 292	not stated; safety; R0007405:Table 3
A2	events	2 / 292	not stated; randomized; R0007405:Figure 1

Nausea (2 lines; O27A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				114 / 287	not stated; safety; R0007405:Table 3
	A2	events				41 / 292	not stated; safety; R0007405:Table 3

Vomiting (2 lines; O27B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				52 / 287	not stated; safety; R0007405:Table 3
	A2	events				4 / 292	not stated; safety; R0007405:Table 3

Diarrhea (2 lines; O27C)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				89 / 287	not stated; safety; R0007405:Table 3
	A2	events				27 / 292	not stated; safety; R0007405:Table 3

Constipation (2 lines; O27D)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				66 / 287	not stated; safety; R0007405:Table 3
	A2	events				20 / 292	not stated; safety; R0007405:Table 3

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

Arm	Statistic	Events / N	Detail
A1	events	2 / 287	not stated; safety; constipation; R0007405:Table 3
A1	events	3 / 287	not stated; safety; diarrhea; R0007405:Table 3
A1	events	3 / 287	not stated; safety; dyspepsia; R0007405:Table 3
A1	events	24 / 287	not stated; safety; nausea; R0007405:Table 3
A1	events	6 / 287	not stated; safety; vomiting; R0007405:Table 3
A2	events	0 / 292	not stated; safety; dyspepsia; R0007405:Table 3
A2	events	0 / 292	not stated; safety; constipation; R0007405:Table 3
A2	events	0 / 292	not stated; safety; diarrhea; R0007405:Table 3
A2	events	4 / 292	not stated; safety; nausea; R0007405:Table 3
A2	events	0 / 292	not stated; safety; vomiting; R0007405:Table 3

Gallbladder and biliary disease (6 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 287	not stated; safety; acute cholecystitis; R0007405:Table 3
A1	events	0 / 287	not stated; safety; chronic cholecystitis; R0007405:Table 3
A1	events	4 / 287	not stated; safety; cholelithiasis; R0007405:Table 3
A2	events	0 / 292	not stated; safety; acute cholecystitis; R0007405:Table 3
A2	events	1 / 292	not stated; safety; chronic cholecystitis; R0007405:Table 3
A2	events	3 / 292	not stated; safety; cholelithiasis; R0007405:Table 3

Acute pancreatitis (6 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 287	not stated; safety; registry:adverse_events
A1	events	1 / 287	not stated; safety; pancreatitis; R0007405:Table 3
A1	events	1 / 287	not stated; safety; pancreatitis; registry:adverse_events
A2	events	1 / 292	not stated; safety; registry:adverse_events
A2	events	1 / 292	not stated; safety; pancreatitis; R0007405:Table 3
A2	events	0 / 292	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				0 / 287	not stated; safety; R0007405:Results
	A2	events				0 / 292	not stated; safety; R0007405:Results

Thyroid cancer (any) (2 lines; O32B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 287	not stated; safety; papillary thyroid cancer; registry:adverse_events
	A2	events				0 / 292	not stated; safety; papillary thyroid cancer; 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	not stated; safety; R0007405:Results
	A2	events				0 / 292	not stated; safety; R0007405:Results

Intestinal obstruction or ileus (2 lines; O37B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 287	not stated; safety; small intestinal obstruction; registry:adverse_events
	A2	events				1 / 292	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 / 287	not stated; safety; R0007405:Results
	A2	events				0 / 292	not stated; safety; R0007405:Results

Any cancer (2 lines; O39)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				5 / 287	not stated; safety; R0007405:Table 3
	A2	events				3 / 292	not stated; safety; R0007405:Table 3