parallel randomized trial

SURPASS-1

A Randomized, Double-blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of Three Tirzepatide Doses Versus Placebo in Patients With Type 2 Diabetes, Inadequately Controlled With Diet and Exercise Alone

Type 2 diabetes (adults)NCT03954834S000407

Design

Randomized: 478
Start year: 2019
Treatment: 40 weeks, follow-up 44 weeks
Countries: India, Japan, Mexico, Puerto Rico, United States
Sponsor: Eli Lilly and Company (industry)
Eligibility: adults; HbA1c 7.0 to 9.5 percent; BMI 23 or higher; no glucose lowering drug in prior 90 days

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
A1	Tirzepatide 5 mg subcutaneous once weekly Tirzepatide 5 mg	none (diet and exercise); lifestyle: not reported	121	121
A2	Tirzepatide 10 mg subcutaneous once weekly Tirzepatide 10 mg	none (diet and exercise); lifestyle: not reported	121	118
A3	Tirzepatide 15 mg subcutaneous once weekly Tirzepatide 15 mg	none (diet and exercise); lifestyle: not reported	121	116
A4	Placebo Placebo	none (diet and exercise); lifestyle: not reported	115	112

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	Placebo A4	Whole trial ALL
age	mean (years)	54.1	55.8	52.9	53.6
age	sd (years)	11.9	10.4	12.3	12.8
asian	n	45	43	42	38
black	n	7	4	6	5
bmi	mean (kg/m2)	32.2	32.2	31.5	31.7
bmi	sd (kg/m2)	6.98	7.65	5.48	6.07
diabetes duration	mean (years)	4.6	4.9	4.8	4.5
diabetes duration	sd (years)	5.08	5.61	4.99	5.87
egfr	mean (mL/min/1.73 m2)					94.1
egfr	sd (mL/min/1.73 m2)					19.7
established cvd	percent					5
female	n	65	49	58	59
female	percent	53.7	40.5	47.9	51.3
hba1c	mean (percent)	8.0	7.9	7.9	8.1
hba1c	sd (percent)	0.84	0.78	1.02	0.80
hispanic	n	50	54	55	48
other race american indian alaska native	n	31	31	30	26
other race multiple	n	0	0	0	0
other race native hawaiian pacific islander	n	0	0	0	0
sbp	mean (mmHg)					127.6
sbp	sd (mmHg)					14.1
weight	mean (kg)	87.0	86.2	85.4	84.8
weight	sd (kg)	21.15	19.50	18.51	20.01
white	n	38	43	43	46

Analyses this trial contributes to

Results

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

HbA1c change (7 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-1.87 percent	0.094		121	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	-1.91 percent		-2.18 to -1.63		hypothetical; modified itt; registry:outcomes
40	A2	change	-1.89 percent	0.096		118	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	-1.93 percent		-2.21 to -1.65		hypothetical; modified itt; registry:outcomes
40	A3	change	-2.07 percent	0.098		116	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-2.11 percent		-2.39 to -1.83		hypothetical; modified itt; registry:outcomes
40	A4	change	0.04 percent	0.105		112	hypothetical; modified itt; registry:outcomes

Body weight change in kilograms (diabetes) (7 lines; O02)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
40	A1	change	-7.0 kg	0.52		121	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	-6.3 kg		-7.8 to -4.7		hypothetical; modified itt; registry:outcomes
40	A2	change	-7.8 kg	0.53		118	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	-7.1 kg		-8.6 to -5.5		hypothetical; modified itt; registry:outcomes
40	A3	change	-9.5 kg	0.54		116	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-8.8 kg		-10.3 to -7.2		hypothetical; modified itt; registry:outcomes
40	A4	change	-0.7 kg	0.57		112	hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	86.78		121	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	or	49.00	21.12 to 113.67		hypothetical; modified itt; registry:outcomes
40	A2	responders	91.53		118	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	80.39	31.80 to 203.19		hypothetical; modified itt; registry:outcomes
40	A3	responders	87.93		116	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	52.95	22.30 to 125.73		hypothetical; modified itt; registry:outcomes
40	A4	responders	19.64		112	hypothetical; modified itt; registry:outcomes

Systolic blood pressure change (5 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	change	-4.7 mmHg		114	not stated; safety; R0009496:Figure 1
40	A2	change	-5.2 mmHg		111	not stated; safety; R0009496:Figure 1
40	A2 vs A4	md	-3.1 mmHg	-6.2 to 0.1		not stated; safety; R0009496:Results
40	A3	change	-4.7 mmHg		105	not stated; safety; R0009496:Figure 1
40	A4	change	-2.0 mmHg		100	not stated; safety; R0009496:Figure 1

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	66.94		121	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	or	12.40	6.43 to 23.94		hypothetical; modified itt; registry:outcomes
40	A2	responders	77.97		118	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	21.13	10.59 to 42.18		hypothetical; modified itt; registry:outcomes
40	A3	responders	76.72		116	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	20.10	10.09 to 40.04		hypothetical; modified itt; registry:outcomes
40	A4	responders	14.29		112	hypothetical; modified itt; registry:outcomes

Weight loss of 10 percent or more (4 lines; O11B)

Week	Arm	Statistic	Estimate	Detail
40	A1	responders	30.6	hypothetical; modified itt; R0007531:Table 2
40	A2	responders	39.8	hypothetical; modified itt; R0007531:Table 2
40	A3	responders	47.4	hypothetical; modified itt; R0007531:Table 2
40	A4	responders	0.9	hypothetical; modified itt; R0007531:Table 2

Weight loss of 15 percent or more (4 lines; O11C)

Week	Arm	Statistic	Estimate	Detail
40	A1	responders	13.2	hypothetical; modified itt; R0007531:Table 2
40	A2	responders	17.0	hypothetical; modified itt; R0007531:Table 2
40	A3	responders	26.7	hypothetical; modified itt; R0007531:Table 2
40	A4	responders	0	hypothetical; modified itt; R0007531:Table 2

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	0 / 121	not stated; safety; registry:adverse_events
A2	events	0 / 121	not stated; safety; registry:adverse_events
A3	events	0 / 121	not stated; safety; registry:adverse_events
A4	events	1 / 115	not stated; safety; registry:adverse_events

Physical functioning (any instrument) (7 lines; O24B)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	change	4.5 points		108	hypothetical; modified itt; R0007531:Supplement Table S3
40	A1 vs A4	md	2.7 points	-1.4 to 6.8		hypothetical; modified itt; R0007531:Supplement Table S3
40	A2	change	4.8 points		104	hypothetical; modified itt; R0007531:Supplement Table S3
40	A2 vs A4	md	3.0 points	-1.1 to 7.1		hypothetical; modified itt; R0007531:Supplement Table S3
40	A3	change	5.9 points		94	hypothetical; modified itt; R0007531:Supplement Table S3
40	A3 vs A4	md	4.0 points	-0.2 to 8.2		hypothetical; modified itt; R0007531:Supplement Table S3
40	A4	change	1.8 points		71	hypothetical; modified itt; R0007531:Supplement Table S3

Health related quality of life total score (any instrument) (7 lines; O24C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	change	0.03 points		108	hypothetical; modified itt; R0007531:Supplement Table S3
40	A1 vs A4	md	0.03 points	-0.01 to 0.07		hypothetical; modified itt; R0007531:Supplement Table S3
40	A2	change	0.03 points		104	hypothetical; modified itt; R0007531:Supplement Table S3
40	A2 vs A4	md	0.03 points	-0.01 to 0.07		hypothetical; modified itt; R0007531:Supplement Table S3
40	A3	change	0.04 points		93	hypothetical; modified itt; R0007531:Supplement Table S3
40	A3 vs A4	md	0.04 points	0.00 to 0.08		hypothetical; modified itt; R0007531:Supplement Table S3
40	A4	change	0.00 points		70	hypothetical; modified itt; R0007531:Supplement Table S3

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	5 / 121	not stated; safety; registry:adverse_events
A2	events	2 / 121	not stated; safety; registry:adverse_events
A3	events	1 / 121	not stated; safety; registry:adverse_events
A4	events	3 / 115	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	4 / 121	not stated; safety; R0007531:Supplement Table S2
A1	events	1 / 121	not stated; randomized; registry:flow
A2	events	6 / 121	not stated; safety; R0007531:Supplement Table S2
A2	events	3 / 121	not stated; randomized; registry:flow
A3	events	8 / 121	not stated; safety; R0007531:Supplement Table S2
A3	events	1 / 121	not stated; randomized; registry:flow
A4	events	3 / 115	not stated; safety; R0007531:Supplement Table S2
A4	events	1 / 115	not stated; randomized; registry:flow

Nausea (8 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	14 / 121	not stated; safety; R0007531:Supplement Table S2
A1	events	14 / 121	not stated; safety; registry:adverse_events
A2	events	16 / 121	not stated; safety; R0007531:Supplement Table S2
A2	events	16 / 121	not stated; safety; registry:adverse_events
A3	events	22 / 121	not stated; safety; R0007531:Supplement Table S2
A3	events	22 / 121	not stated; safety; registry:adverse_events
A4	events	7 / 115	not stated; safety; R0007531:Supplement Table S2
A4	events	7 / 115	not stated; safety; registry:adverse_events

Vomiting (8 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	4 / 121	not stated; safety; R0007531:Supplement Table S2
A1	events	4 / 121	not stated; safety; registry:adverse_events
A2	events	3 / 121	not stated; safety; R0007531:Supplement Table S2
A2	events	3 / 121	not stated; safety; registry:adverse_events
A3	events	7 / 121	not stated; safety; R0007531:Supplement Table S2
A3	events	7 / 121	not stated; safety; registry:adverse_events
A4	events	2 / 115	not stated; safety; R0007531:Supplement Table S2
A4	events	2 / 115	not stated; safety; registry:adverse_events

Diarrhea (8 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	14 / 121	not stated; safety; R0007531:Supplement Table S2
A1	events	14 / 121	not stated; safety; registry:adverse_events
A2	events	17 / 121	not stated; safety; R0007531:Supplement Table S2
A2	events	17 / 121	not stated; safety; registry:adverse_events
A3	events	14 / 121	not stated; safety; R0007531:Supplement Table S2
A3	events	14 / 121	not stated; safety; registry:adverse_events
A4	events	9 / 115	not stated; safety; R0007531:Supplement Table S2
A4	events	9 / 115	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	7 / 121	not stated; safety; registry:adverse_events
A2	events	6 / 121	not stated; safety; registry:adverse_events
A3	events	8 / 121	not stated; safety; registry:adverse_events
A4	events	1 / 115	not stated; safety; registry:adverse_events