parallel randomized trial

SURPASS-5

Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide Versus Placebo in Patients With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Type 2 diabetes (adults)NCT04039503S001608

Design

Randomized: 475
Start year: 2019
Treatment: 40 weeks, follow-up 44 weeks
Countries: Czechia, Germany, Japan, Poland, Puerto Rico, Slovakia, Spain, United States
Sponsor: Eli Lilly and Company (industry)
Eligibility: HbA1c 7.0 to 10.5 percent; BMI 23 or higher; insulin glargine above 0.25 U/kg or 20 U daily with or without metformin

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	insulin glargine titrated to target with or without metformin; lifestyle: not reported	116	115
A2	Tirzepatide 10 mg subcutaneous once weekly Tirzepatide 10 mg	insulin glargine titrated to target with or without metformin; lifestyle: not reported	119	113
A3	Tirzepatide 15 mg subcutaneous once weekly Tirzepatide 15 mg	insulin glargine titrated to target with or without metformin; lifestyle: not reported	120	117
A4	Placebo Placebo	insulin glargine titrated to target with or without metformin; lifestyle: not reported	120	118

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)	61.50	60.40	60.50	60.00
age	sd (years)	9.81	10.24	9.92	9.63
asian	n	20	21	22	22
black	n	1	2	3	0
bmi	mean (kg/m2)					33.4
bmi	sd (kg/m2)					6.1
diabetes duration	mean (years)					13.3
diabetes duration	sd (years)					7.3
egfr	mean (mL/min/1.73m2)					85.5
egfr	sd (mL/min/1.73m2)					17.8
established cvd	percent					18
female	n	55	47	55	54
hba1c	mean (percent)	8.30	8.36	8.23	8.37
hba1c	sd (percent)	0.88	0.83	0.86	0.84
hispanic	n	4	8	5	5
insulin dose	mean (U/day)					37.6
insulin dose	sd (U/day)					22.7
insulin use	percent					100.0
metformin use	n					394
metformin use	percent					82.9
other american indian	n	0	1	1	0
other multiple race	n	0	1	0	1
sbp	mean (mmHg)					137.9
sbp	sd (mmHg)					15.7
weight	mean (kg)					95.2
weight	sd (kg)					21.6
white	n	95	94	94	97

Analyses this trial contributes to

Results

100 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	-2.23 percent	0.081		115	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	-1.30 percent		-1.52 to -1.07		hypothetical; modified itt; registry:outcomes
40	A2	change	-2.59 percent	0.081		113	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	-1.66 percent		-1.88 to -1.43		hypothetical; modified itt; registry:outcomes
40	A3	change	-2.59 percent	0.083		117	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-1.65 percent		-1.88 to -1.43		hypothetical; modified itt; registry:outcomes
40	A4	change	-0.93 percent	0.079		118	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	-6.2 kg	0.58		115	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	md	-7.8 kg		-9.4 to -6.3		hypothetical; modified itt; registry:outcomes
40	A2	change	-8.2 kg	0.58		113	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	md	-9.9 kg		-11.5 to -8.3		hypothetical; modified itt; registry:outcomes
40	A3	change	-10.9 kg	0.59		117	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	md	-12.6 kg		-14.2 to -11.0		hypothetical; modified itt; registry:outcomes
40	A4	change	1.7 kg	0.57		118	hypothetical; modified itt; registry:outcomes

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	responders	93.04		115	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	or	37.77	15.23 to 93.70		hypothetical; modified itt; registry:outcomes
40	A2	responders	97.35		113	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	100.07	30.02 to 333.62		hypothetical; modified itt; registry:outcomes
40	A3	responders	94.02		117	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	43.31	16.92 to 110.83		hypothetical; modified itt; registry:outcomes
40	A4	responders	33.90		118	hypothetical; modified itt; registry:outcomes

Level 2 or 3 hypoglycemia (episode rate) (4 lines; O04B)

Arm	Statistic	Estimate	SE or SD	Events / N	Detail
A1	rate	0.49	0.141	116	not stated; safety; registry:outcomes
A2	rate	0.66	0.169	119	not stated; safety; registry:outcomes
A3	rate	0.38	0.099	120	not stated; safety; registry:outcomes
A4	rate	0.51	0.149	120	not stated; safety; registry:outcomes

Systolic blood pressure change (7 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	change	-6.1 mmHg		109	treatment policy; safety; R0009496:Figure 1
40	A1 vs A4	md	-4.4 mmHg	-7.8 to -1.0		treatment policy; safety; R0009496:Results
40	A2	change	-8.3 mmHg		115	treatment policy; safety; R0009496:Figure 1
40	A2 vs A4	md	-6.6 mmHg	-9.9 to -3.2		treatment policy; safety; R0009496:Results
40	A3	change	-12.6 mmHg		110	treatment policy; safety; R0009496:Figure 1
40	A3 vs A4	md	-10.9 mmHg	-14.3 to -7.5		treatment policy; safety; R0009496:Results
40	A4	change	-1.7 mmHg		117	treatment policy; 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	53.91		115	hypothetical; modified itt; registry:outcomes
40	A1 vs A4	or	17.15	7.55 to 38.93		hypothetical; modified itt; registry:outcomes
40	A2	responders	64.60		113	hypothetical; modified itt; registry:outcomes
40	A2 vs A4	or	27.24	11.87 to 62.55		hypothetical; modified itt; registry:outcomes
40	A3	responders	84.62		117	hypothetical; modified itt; registry:outcomes
40	A3 vs A4	or	79.61	32.76 to 193.44		hypothetical; modified itt; registry:outcomes
40	A4	responders	5.93		118	hypothetical; modified itt; registry:outcomes

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

Week	Arm	Statistic	Estimate	Detail
40	A1	responders	22.6	hypothetical; modified itt; R0007531:Table 2
40	A2	responders	46.9	hypothetical; modified itt; R0007531:Table 2
40	A3	responders	51.3	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	7.0	hypothetical; modified itt; R0007531:Table 2
40	A2	responders	26.6	hypothetical; modified itt; R0007531:Table 2
40	A3	responders	31.6	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 / 116	not stated; safety; registry:adverse_events
A2	events	0 / 119	not stated; safety; registry:adverse_events
A3	events	0 / 120	not stated; safety; registry:adverse_events
A4	events	0 / 120	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	1.6 points		106	hypothetical; modified itt; R0007531:Supplement Table S3
40	A1 vs A4	md	3.0 points	-1.0 to 6.9		hypothetical; modified itt; R0007531:Supplement Table S3
40	A2	change	5.0 points		106	hypothetical; modified itt; R0007531:Supplement Table S3
40	A2 vs A4	md	6.3 points	2.3 to 10.3		hypothetical; modified itt; R0007531:Supplement Table S3
40	A3	change	6.9 points		98	hypothetical; modified itt; R0007531:Supplement Table S3
40	A3 vs A4	md	8.3 points	4.2 to 12.3		hypothetical; modified itt; R0007531:Supplement Table S3
40	A4	change	-1.3 points		111	hypothetical; modified itt; R0007531:Supplement Table S3

Health related quality of life total score (any instrument) (14 lines; O24C)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
40	A1	change	-0.02 points		105	hypothetical; modified itt; R0007531:Supplement Table S3
40	A1	final	14.1 points		105	hypothetical; modified itt; R0007531:Supplement Table S3
40	A1 vs A4	md	3.4 points	1.9 to 4.8		hypothetical; modified itt; R0007531:Supplement Table S3
40	A1 vs A4	md	0.01 points	-0.03 to 0.05		hypothetical; modified itt; R0007531:Supplement Table S3
40	A2	change	0.04 points		105	hypothetical; modified itt; R0007531:Supplement Table S3
40	A2	final	14.5 points		105	hypothetical; modified itt; R0007531:Supplement Table S3
40	A2 vs A4	md	3.7 points	2.3 to 5.2		hypothetical; modified itt; R0007531:Supplement Table S3
40	A2 vs A4	md	0.07 points	0.03 to 0.11		hypothetical; modified itt; R0007531:Supplement Table S3
40	A3	change	0.03 points		98	hypothetical; modified itt; R0007531:Supplement Table S3
40	A3	final	13.7 points		95	hypothetical; modified itt; R0007531:Supplement Table S3
40	A3 vs A4	md	2.9 points	1.4 to 4.4		hypothetical; modified itt; R0007531:Supplement Table S3
40	A3 vs A4	md	0.06 points	0.02 to 0.11		hypothetical; modified itt; R0007531:Supplement Table S3
40	A4	change	-0.03 points		111	hypothetical; modified itt; R0007531:Supplement Table S3
40	A4	final	10.7 points		109	hypothetical; modified itt; R0007531:Supplement Table S3

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	9 / 116	not stated; safety; registry:adverse_events
A2	events	13 / 119	not stated; safety; registry:adverse_events
A3	events	9 / 120	not stated; safety; registry:adverse_events
A4	events	10 / 120	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (8 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	7 / 116	not stated; safety; R0007531:Supplement Table S2
A1	events	3 / 116	not stated; randomized; registry:flow
A2	events	10 / 119	not stated; safety; R0007531:Supplement Table S2
A2	events	0 / 119	not stated; randomized; registry:flow
A3	events	13 / 120	not stated; safety; R0007531:Supplement Table S2
A3	events	2 / 120	not stated; randomized; registry:flow
A4	events	3 / 120	not stated; safety; R0007531:Supplement Table S2
A4	events	0 / 120	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	15 / 116	not stated; safety; R0007531:Supplement Table S2
A2	events	21 / 119	not stated; safety; R0007531:Supplement Table S2
A3	events	22 / 120	not stated; safety; R0007531:Supplement Table S2
A4	events	3 / 120	not stated; safety; R0007531:Supplement Table S2

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	8 / 116	not stated; safety; R0007531:Supplement Table S2
A2	events	9 / 119	not stated; safety; R0007531:Supplement Table S2
A3	events	15 / 120	not stated; safety; R0007531:Supplement Table S2
A4	events	3 / 120	not stated; safety; R0007531:Supplement Table S2

Diarrhea (4 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	14 / 116	not stated; safety; R0007531:Supplement Table S2
A2	events	15 / 119	not stated; safety; R0007531:Supplement Table S2
A3	events	25 / 120	not stated; safety; R0007531:Supplement Table S2
A4	events	12 / 120	not stated; safety; R0007531:Supplement Table S2

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	7 / 116	not stated; safety; registry:adverse_events
A2	events	8 / 119	not stated; safety; registry:adverse_events
A3	events	8 / 120	not stated; safety; registry:adverse_events
A4	events	2 / 120	not stated; safety; registry:adverse_events