parallel randomized trial

SURPASS-3

A Randomized, Phase 3, Open-Label Trial Comparing the Effect of LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes

Type 2 diabetes (adults)NCT03882970S001591

Design

Randomized: 1,444
Start year: 2019
Treatment: 52 weeks, follow-up 56 weeks
Countries: multinational
Sponsor: Eli Lilly and Company (industry)
Eligibility: insulin naive; HbA1c 7.0 to 10.5 percent; BMI at least 25; metformin with or without SGLT2i; eGFR above 45

Conduct and analysis

Blinding: open label
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	metformin with or without SGLT2 inhibitor; lifestyle: not reported	359	312
A2	Tirzepatide 10 mg subcutaneous once weekly Tirzepatide 10 mg	metformin with or without SGLT2 inhibitor; lifestyle: not reported	361	291
A3	Tirzepatide 15 mg subcutaneous once weekly Tirzepatide 15 mg	metformin with or without SGLT2 inhibitor; lifestyle: not reported	359	294
A4	Insulin degludec Insulin degludec	metformin with or without SGLT2 inhibitor; lifestyle: not reported	365	317

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	Insulin degludec A4	Whole trial ALL
age	mean (years)	57.20	57.40	57.50	57.50
age	sd (years)	10.13	9.66	10.24	10.08
asian	n	20	19	20	19
black	n	13	12	8	11
bmi	mean (kg/m2)					33.5
bmi	sd (kg/m2)					6.1
diabetes duration	mean (years)					8.4
diabetes duration	sd (years)					6.2
egfr	mean (mL/min/1.73 m2)					94.1
egfr	sd (mL/min/1.73 m2)					17.0
established cvd	percent					13
female	n	158	165	165	148
hba1c	mean (percent)	8.17	8.18	8.21	8.12
hba1c	sd (percent)	0.89	0.89	0.94	0.94
hispanic	n	109	108	96	108
metformin use	percent					100
other race american indian alaska native	n	0	1	1	2
other race multiple	n	1	0	1	0
other race native hawaiian pacific islander	n	1	0	2	1
sbp	mean (mmHg)					131.5
sbp	sd (mmHg)					13.3
sglt2i use	n					458
sglt2i use	percent					32
weight	mean (kg)					94.3
weight	sd (kg)					20.1
white	n	324	329	327	332

Analyses this trial contributes to

Results

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

HbA1c change (11 lines; O01)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
24	A1	change	-1.91 percent	0.044			hypothetical; modified itt; R0007660:Table 1
24	A2	change	-2.14 percent	0.045			hypothetical; modified itt; R0007660:Table 1
24	A3	change	-2.24 percent	0.045			hypothetical; modified itt; R0007660:Table 1
24	A4	change	-1.36 percent	0.045			hypothetical; modified itt; R0007660:Table 1
52	A1	change	-1.93 percent	0.05		312	hypothetical; modified itt; R0007531:Table 2
52	A1 vs A4	md	-0.59 percent		-0.73 to -0.45		hypothetical; modified itt; registry:outcomes
52	A2 vs A4	md	-0.86 percent		-1.00 to -0.72		hypothetical; modified itt; registry:outcomes
52	A2	change	-2.20 percent	0.05		291	hypothetical; modified itt; R0007531:Table 2
52	A3	change	-2.37 percent	0.05		294	hypothetical; modified itt; R0007531:Table 2
52	A3 vs A4	md	-1.04 percent		-1.17 to -0.90		hypothetical; modified itt; registry:outcomes
52	A4	change	-1.34 percent	0.05		317	hypothetical; modified itt; R0007531:Table 2

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1	change	-7.5 kg	0.4		310	hypothetical; modified itt; R0007531:Table 2
52	A1 vs A4	md	-9.8 kg		-10.8 to -8.8		hypothetical; modified itt; registry:outcomes
52	A2	change	-10.7 kg	0.4		291	hypothetical; modified itt; R0007531:Table 2
52	A2 vs A4	md	-13.0 kg		-14.0 to -11.9		hypothetical; modified itt; registry:outcomes
52	A3 vs A4	md	-15.2 kg		-16.2 to -14.2		hypothetical; modified itt; registry:outcomes
52	A3	change	-12.9 kg	0.4		295	hypothetical; modified itt; R0007531:Table 2
52	A4	change	2.3 kg	0.4		317	hypothetical; modified itt; R0007531:Table 2

HbA1c below 7 percent (7 lines; O03)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	82.44		353	hypothetical; modified itt; registry:outcomes
52	A1 vs A4	or	3.45	2.38 to 5.01		hypothetical; modified itt; registry:outcomes
52	A2	responders	89.71		350	hypothetical; modified itt; registry:outcomes
52	A2 vs A4	or	7.02	4.55 to 10.84		hypothetical; modified itt; registry:outcomes
52	A3	responders	92.63		353	hypothetical; modified itt; registry:outcomes
52	A3 vs A4	or	10.79	6.65 to 17.48		hypothetical; modified itt; registry:outcomes
52	A4	responders	61.25		351	hypothetical; modified itt; registry:outcomes

Level 2 or 3 hypoglycemia (participants) (4 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	5 / 358	not stated; safety; R0007214:Table 2
A2	events	4 / 360	not stated; safety; R0007214:Table 2
A3	events	8 / 359	not stated; safety; R0007214:Table 2
A4	events	26 / 360	not stated; safety; R0007214:Table 2

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

Arm	Statistic	Estimate	SE or SD	Events / N	Detail
A1	rate	0.0137	0.0056	356	hypothetical; modified itt; registry:outcomes
A2	rate	0.0108	0.0044	360	hypothetical; modified itt; registry:outcomes
A3	rate	0.0275	0.0143	359	hypothetical; modified itt; registry:outcomes
A4	rate	0.1020	0.0568	358	hypothetical; modified itt; registry:outcomes

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Detail
40	A1 vs A4	md	-4.9 mmHg	-6.8 to -3.0	treatment policy; safety; R0009496:Results
40	A2 vs A4	md	-6.3 mmHg	-8.2 to -4.4	treatment policy; safety; R0009496:Results
40	A3 vs A4	md	-6.9 mmHg	-8.8 to -5.0	treatment policy; safety; R0009496:Results

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	responders	66.0		353	hypothetical; modified itt; R0007531:Table 2
52	A1 vs A4	or	29.78	18.35 to 48.35		hypothetical; modified itt; registry:outcomes
52	A2	responders	83.7		350	hypothetical; modified itt; R0007531:Table 2
52	A2 vs A4	or	79.88	47.56 to 134.17		hypothetical; modified itt; registry:outcomes
52	A3	responders	87.8		353	hypothetical; modified itt; R0007531:Table 2
52	A3 vs A4	or	110.77	64.73 to 189.55		hypothetical; modified itt; registry:outcomes
52	A4	responders	6.3		351	hypothetical; modified itt; R0007531:Table 2

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

Week	Arm	Statistic	Estimate	Detail
52	A1	responders	37.4	hypothetical; modified itt; R0007531:Table 2
52	A2	responders	55.7	hypothetical; modified itt; R0007531:Table 2
52	A3	responders	69.4	hypothetical; modified itt; R0007531:Table 2
52	A4	responders	2.9	hypothetical; modified itt; R0007531:Table 2

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

Week	Arm	Statistic	Estimate	Detail
52	A1	responders	12.5	hypothetical; modified itt; R0007531:Table 2
52	A2	responders	28.3	hypothetical; modified itt; R0007531:Table 2
52	A3	responders	42.5	hypothetical; modified itt; R0007531:Table 2
52	A4	responders	0	hypothetical; modified itt; R0007531:Table 2

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; registry:adverse_events
A2	events	0 / 360	not stated; safety; registry:adverse_events
A3	events	0 / 359	not stated; safety; registry:adverse_events
A4	events	1 / 360	not stated; safety; registry:adverse_events

All cause mortality (4 lines; O20)

Arm	Statistic	Events / N	Detail
A1	events	1 / 358	not stated; safety; R0015264:Table 2
A2	events	2 / 360	not stated; safety; R0015264:Table 2
A3	events	1 / 359	not stated; safety; R0015264:Table 2
A4	events	1 / 360	not stated; safety; registry:adverse_events

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

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
52	A1	change	3.0 points		312	hypothetical; modified itt; R0007531:Supplement Table S3
52	A1 vs A4	md	4.0 points	1.6 to 6.4		hypothetical; modified itt; R0007531:Supplement Table S3
52	A2	change	5.5 points		297	hypothetical; modified itt; R0007531:Supplement Table S3
52	A2 vs A4	md	6.5 points	4.1 to 8.9		hypothetical; modified itt; R0007531:Supplement Table S3
52	A3	change	6.3 points		297	hypothetical; modified itt; R0007531:Supplement Table S3
52	A3 vs A4	md	7.3 points	4.9 to 9.7		hypothetical; modified itt; R0007531:Supplement Table S3
52	A4	change	-1.0 points		320	hypothetical; modified itt; R0007531:Supplement Table S3

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

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
52	A1 vs A4	md	0.01 points		-0.01 to 0.03		hypothetical; modified itt; R0007531:Supplement Table S3
52	A1	change	0.02 points			309	hypothetical; modified itt; R0007531:Supplement Table S3
52	A1	final	15.6 points	0.27		306	hypothetical; modified itt; registry:outcomes
52	A1 vs A4	md	3.0 points		2.3 to 3.8		hypothetical; modified itt; R0007531:Supplement Table S3
52	A2	final	15.5 points	0.28		293	hypothetical; modified itt; registry:outcomes
52	A2	change	0.03 points			295	hypothetical; modified itt; R0007531:Supplement Table S3
52	A2 vs A4	md	2.9 points		2.2 to 3.7		hypothetical; modified itt; R0007531:Supplement Table S3
52	A2 vs A4	md	0.02 points		0.00 to 0.04		hypothetical; modified itt; R0007531:Supplement Table S3
52	A3	change	0.03 points			294	hypothetical; modified itt; R0007531:Supplement Table S3
52	A3	final	15.6 points	0.28		292	hypothetical; modified itt; registry:outcomes
52	A3 vs A4	md	3.0 points		2.2 to 3.7		hypothetical; modified itt; R0007531:Supplement Table S3
52	A3 vs A4	md	0.02 points		0.00 to 0.04		hypothetical; modified itt; R0007531:Supplement Table S3
52	A4	change	0.01 points			318	hypothetical; modified itt; R0007531:Supplement Table S3
52	A4	final	12.6 points	0.27		313	hypothetical; modified itt; registry:outcomes

Serious adverse events (4 lines; O25)

Arm	Statistic	Events / N	Detail
A1	events	29 / 358	not stated; safety; R0015264:Table 2
A2	events	20 / 360	not stated; safety; R0015264:Table 2
A3	events	26 / 359	not stated; safety; R0015264:Table 2
A4	events	22 / 360	not stated; safety; registry:adverse_events

Discontinuation due to adverse events (11 lines; O26)

Arm	Statistic	Events / N	Detail
A1	events	25 / 358	not stated; safety; R0015264:Table 2
A1	events	6 / 358	not stated; safety; R0015264:Table 2
A1	events	5 / 359	not stated; randomized; registry:flow
A2	events	37 / 360	not stated; safety; R0015264:Table 2
A2	events	9 / 360	not stated; safety; R0015264:Table 2
A2	events	7 / 361	not stated; randomized; registry:flow
A3	events	39 / 359	not stated; safety; R0015264:Table 2
A3	events	4 / 359	not stated; safety; R0015264:Table 2
A3	events	3 / 359	not stated; randomized; registry:flow
A4	events	5 / 360	not stated; safety; R0007531:Supplement Table S2
A4	events	1 / 365	not stated; randomized; registry:flow

Nausea (4 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	41 / 358	not stated; safety; R0015264:Table 2
A2	events	81 / 360	not stated; safety; R0015264:Table 2
A3	events	85 / 359	not stated; safety; R0015264:Table 2
A4	events	6 / 360	not stated; safety; R0007531:Supplement Table S2

Vomiting (4 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	21 / 358	not stated; safety; R0015264:Table 2
A2	events	34 / 360	not stated; safety; R0015264:Table 2
A3	events	36 / 359	not stated; safety; R0015264:Table 2
A4	events	4 / 360	not stated; safety; R0007531:Supplement Table S2

Diarrhea (9 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; registry:adverse_events
A1	events	55 / 358	not stated; safety; R0015264:Table 2
A2	events	60 / 360	not stated; safety; R0015264:Table 2
A2	events	59 / 360	not stated; safety; registry:adverse_events
A2	events	1 / 360	not stated; safety; registry:adverse_events
A3	events	56 / 359	not stated; safety; R0015264:Table 2
A3	events	0 / 359	not stated; safety; registry:adverse_events
A4	events	14 / 360	not stated; safety; R0007531:Supplement Table S2
A4	events	0 / 360	not stated; safety; registry:adverse_events

Constipation (7 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; registry:adverse_events
A1	events	11 / 358	not stated; safety; R0015264:Table 2
A2	events	13 / 360	not stated; safety; R0015264:Table 2
A2	events	1 / 360	not stated; safety; registry:adverse_events
A3	events	17 / 359	not stated; safety; R0015264:Table 2
A3	events	0 / 359	not stated; safety; registry:adverse_events
A4	events	0 / 360	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (8 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; Cholecystitis; registry:adverse_events
A1	events	1 / 358	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	1 / 360	not stated; safety; Cholelithiasis; registry:adverse_events
A2	events	0 / 360	not stated; safety; Cholecystitis; registry:adverse_events
A3	events	1 / 359	not stated; safety; Cholecystitis; registry:adverse_events
A3	events	1 / 359	not stated; safety; Cholelithiasis; registry:adverse_events
A4	events	0 / 360	not stated; safety; Cholecystitis; registry:adverse_events
A4	events	0 / 360	not stated; safety; Cholelithiasis; registry:adverse_events

Acute pancreatitis (4 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; registry:adverse_events
A2	events	1 / 360	not stated; safety; registry:adverse_events
A3	events	0 / 359	not stated; safety; registry:adverse_events
A4	events	0 / 360	not stated; safety; registry:adverse_events

Suicidal ideation or behavior (8 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	0 / 358	not stated; safety; Depression suicidal; registry:adverse_events
A1	events	0 / 358	not stated; safety; Suicide attempt; registry:adverse_events
A2	events	0 / 360	not stated; safety; Depression suicidal; registry:adverse_events
A2	events	0 / 360	not stated; safety; Suicide attempt; registry:adverse_events
A3	events	1 / 359	not stated; safety; Depression suicidal; registry:adverse_events
A3	events	0 / 359	not stated; safety; Suicide attempt; registry:adverse_events
A4	events	0 / 360	not stated; safety; Depression suicidal; registry:adverse_events
A4	events	1 / 360	not stated; safety; Suicide attempt; registry:adverse_events