parallel randomized trial

SURPASS-CVOT

The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT)

Type 2 diabetes (adults)NCT04255433S002212

Design

Randomized: 13,299
Start year: 2020
Treatment: 260.9 weeks, follow-up 259 weeks
Countries: multinational (640 sites)
Sponsor: Eli Lilly and Company (industry)
Eligibility: age 40 or older; type 2 diabetes; HbA1c 7.0 to 10.5 percent; BMI 25 or more; established atherosclerotic cardiovascular disease

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: censored at last known contact

Arms

Arm	Treatment	Background	Randomized	Analyzed	Completed treatment
A1	tirzepatide Tirzepatide up to 15 mg or maximum tolerated dose	usual glucose lowering therapy at investigator discretion; DPP4 inhibitors stopped; lifestyle: standard	6,648	6,586
A2	Dulaglutide 1.5 mg subcutaneous once weekly Dulaglutide 1.5 mg	usual glucose lowering care; DPP4 inhibitor stop recommended; lifestyle: standard	6,651	6,579

Baseline characteristics

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

Characteristic	Statistic	Tirzepatide up to 15 mg or maximum tolerated dose A1	Dulaglutide 1.5 mg subcutaneous once weekly A2	Whole trial ALL
age	mean (years)	64.0	64.1
age	sd (years)	8.8	8.7
asian	n	580	590
black	n	111	109
bmi	mean (kg/m2)	32.6	32.6
bmi	sd (kg/m2)	5.5	5.5
diabetes duration	mean (years)	14.8	14.7
diabetes duration	sd (years)	8.8	8.7
egfr: less than 60	n	1516	1412
egfr: less than 60	percent	23.4	21.7
egfr	mean (mL/min/1.73 m2)	78.5	79.2
egfr	sd (mL/min/1.73 m2)	24.2	23.5
established cvd: coronary artery disease	n	4286	4267
established cvd: coronary artery disease	percent	65.1	64.9
established cvd: coronary revascularization	n	3756	3773
established cvd: coronary revascularization	percent	57.0	57.3
established cvd: heart failure	n	1310	1368
established cvd: heart failure	percent	19.9	20.8
established cvd: myocardial infarction	n	3097	3119
established cvd: myocardial infarction	percent	47.0	47.4
established cvd: peripheral artery disease	n	1660	1674
established cvd: peripheral artery disease	percent	25.2	25.4
established cvd: stroke	n	1253	1272
established cvd: stroke	percent	19.0	19.3
female	n	1891	1926
female	percent	28.7	29.3
hba1c	mean (percent)	8.40	8.38
hba1c	sd (percent)	0.92	0.93
hispanic	n	1988	1981
hispanic	percent	30.2	30.1
insulin use	percent			48.8
metformin use	percent			81.4
other race american indian alaska native	n	489	481
other race multiple	n	22	26
other race native hawaiian pacific islander	n	9	9
other sulfonylurea use	percent			21.6
sbp	mean (mmHg)	135.1	135.5
sbp	sd (mmHg)	15.5	15.8
sglt2i use	n			4027
sglt2i use	percent			30.6
uacr: macroalbuminuria	n	754	737
uacr: macroalbuminuria	percent	11.7	11.4
uacr: microalbuminuria	n	2072	2070
uacr: microalbuminuria	percent	32.0	31.9
uacr	median (mg/g)	22.0	22.0
uacr	q1 (mg/g)	9.0	9.0
uacr	q3 (mg/g)	86.0	81.0
weight	mean (kg)	92.6	92.5
weight	sd (kg)	18.9	18.8
white	n	5299	5282
white	percent	81.5	81.4

Results

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

HbA1c change (3 lines; O01)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
156.42	A1	change	-1.66 percent	-1.70 to -1.62	6586	treatment policy; modified itt; R0009202:Table 2
156.42	A1 vs A2	md	-0.78 percent	-0.84 to -0.72		treatment policy; modified itt; R0009202:Table 2
156.42	A2	change	-0.88 percent	-0.92 to -0.83	6579	treatment policy; modified itt; R0009202:Table 2

Level 2 or 3 hypoglycemia (participants) (8 lines; O04)

Arm	Statistic	Events / N	Detail
A1	events	0 / 6647	not stated; safety; registry:adverse_events
A1	events	49 / 6647	not stated; safety; R0009202:Table 3
A1	events	6 / 6647	not stated; safety; registry:adverse_events
A1	events	44 / 6647	not stated; safety; registry:adverse_events
A2	events	39 / 6647	not stated; safety; registry:adverse_events
A2	events	48 / 6647	not stated; safety; R0009202:Table 3
A2	events	2 / 6647	not stated; safety; registry:adverse_events
A2	events	9 / 6647	not stated; safety; registry:adverse_events

Level 2 or 3 hypoglycemia (episode rate) (6 lines; O04B)

Arm	Statistic	Events / N	Detail
A1	rate	6647	not stated; safety; registry:adverse_events
A1	rate	6647	not stated; safety; registry:adverse_events
A1	rate	6647	not stated; safety; registry:adverse_events
A2	rate	6647	not stated; safety; registry:adverse_events
A2	rate	6647	not stated; safety; registry:adverse_events
A2	rate	6647	not stated; safety; registry:adverse_events

Systolic blood pressure change (3 lines; O05)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
156.42	A1 vs A2	md	-2.1 mmHg	-2.6 to -1.5		not stated; modified itt; R0009202:Table 2
156.42	A1	change	-6.2 mmHg	-6.6 to -5.8	6586	not stated; modified itt; R0009202:Table 2
156.42	A2	change	-4.1 mmHg	-4.6 to -3.7	6579	not stated; modified itt; R0009202:Table 2

Percent body weight change (3 lines; O10)

Week	Arm	Statistic	Estimate	95% CI	Events / N	Detail
156.42	A1	percent change	-11.6 percent	-11.8 to -11.4	6586	not stated; modified itt; R0009202:Table 2
156.42	A1 vs A2	md	-6.8 percent	-7.1 to -6.5		not stated; modified itt; R0009202:Table 2
156.42	A2	percent change	-4.8 percent	-5.0 to -4.6	6578	not stated; modified itt; R0009202:Table 2

Acute kidney injury (4 lines; O121)

Arm	Statistic	Events / N	Detail
A1	events	226 / 6647	not stated; safety; R0009202:Table 3
A1	events	93 / 6647	not stated; safety; registry:adverse_events
A2	events	178 / 6647	not stated; safety; R0009202:Table 3
A2	events	92 / 6647	not stated; safety; registry:adverse_events

All cause mortality (5 lines; O20)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			566 / 6586	treatment policy; modified itt; R0009202:Table 2
A1	events			568 / 6648	not stated; randomized; registry:adverse_events
A1 vs A2	hr	0.84	0.75 to 0.94		treatment policy; modified itt; R0009202:Table 2
A2	events			670 / 6651	not stated; randomized; registry:adverse_events
A2	events			669 / 6579	treatment policy; modified itt; R0009202:Table 2

Three point MACE (5 lines; O21)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			801 / 6586	treatment policy; modified itt; R0009202:Table 2
A1 vs A2	competing hr	0.75	0.63 to 0.91		treatment policy; modified itt; R0009202:Results
A1 vs A2	hr	0.92	0.83 to 1.01		treatment policy; modified itt; R0009202:Table 2
A1 vs A2	hr	0.92	0.84 to 1.02		treatment policy; modified itt; R0009202:Results
A2	events			862 / 6579	treatment policy; modified itt; R0009202:Table 2

Kidney composite including albuminuria or smaller eGFR declines (5 lines; O22E)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			326 / 6586	treatment policy; modified itt; R0006080:Table 2
A1	events			373 / 6586	not stated; modified itt; registry:outcomes
A1 vs A2	hr	0.79	0.68 to 0.91		treatment policy; modified itt; R0006080:Table 2
A2	events			404 / 6579	treatment policy; modified itt; R0006080:Table 2
A2	events			442 / 6579	not stated; modified itt; registry:outcomes

Hospitalization for heart failure (15 lines; O23)

Arm	Statistic	Estimate	95% CI	Events / N	Detail
A1	events			9 / 6647	not stated; safety; cardiac failure congestive; registry:adverse_events
A1	events			34 / 6647	not stated; safety; cardiac failure; registry:adverse_events
A1	events			2 / 6647	not stated; safety; heart failure with preserved ejection fraction; registry:adverse_events
A1	events			3 / 6647	not stated; safety; cardiac failure acute; registry:adverse_events
A1	events			1 / 6647	not stated; safety; heart failure with reduced ejection fraction; registry:adverse_events
A1	events			198 / 6586	treatment policy; modified itt; R0006080:Table 2
A1 vs A2	hr	0.96	0.79 to 1.17		treatment policy; modified itt; R0006080:Table 2
A1	events			62 / 6647	not stated; safety; cardiac failure chronic; registry:adverse_events
A2	events			8 / 6647	not stated; safety; cardiac failure acute; registry:adverse_events
A2	events			204 / 6579	treatment policy; modified itt; R0006080:Table 2
A2	events			62 / 6647	not stated; safety; cardiac failure chronic; registry:adverse_events
A2	events			15 / 6647	not stated; safety; cardiac failure congestive; registry:adverse_events
A2	events			36 / 6647	not stated; safety; cardiac failure; registry:adverse_events
A2	events			1 / 6647	not stated; safety; heart failure with preserved ejection fraction; registry:adverse_events
A2	events			3 / 6647	not stated; safety; heart failure with reduced ejection fraction; registry:adverse_events

Serious adverse events (2 lines; O25)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2117 / 6647	not stated; safety; R0009202:Table 3
	A2	events				2121 / 6647	not stated; safety; R0009202:Table 3

Discontinuation due to adverse events (2 lines; O26)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				878 / 6647	not stated; safety; R0009202:Table 3
	A2	events				672 / 6647	not stated; safety; R0009202:Table 3

Nausea (6 lines; O27A)

Arm	Statistic	Events / N	Detail
A1	events	1667 / 6647	not stated; safety; R0009202:Table 3
A1	events	1665 / 6647	not stated; safety; registry:adverse_events
A1	events	5 / 6647	not stated; safety; registry:adverse_events
A2	events	1486 / 6647	not stated; safety; R0009202:Table 3
A2	events	1484 / 6647	not stated; safety; registry:adverse_events
A2	events	6 / 6647	not stated; safety; registry:adverse_events

Vomiting (6 lines; O27B)

Arm	Statistic	Events / N	Detail
A1	events	20 / 6647	not stated; safety; registry:adverse_events
A1	events	772 / 6647	not stated; safety; R0009202:Table 3
A1	events	757 / 6647	not stated; safety; registry:adverse_events
A2	events	637 / 6647	not stated; safety; registry:adverse_events
A2	events	642 / 6647	not stated; safety; R0009202:Table 3
A2	events	9 / 6647	not stated; safety; registry:adverse_events

Diarrhea (6 lines; O27C)

Arm	Statistic	Events / N	Detail
A1	events	1644 / 6647	not stated; safety; registry:adverse_events
A1	events	1651 / 6647	not stated; safety; R0009202:Table 3
A1	events	13 / 6647	not stated; safety; registry:adverse_events
A2	events	1258 / 6647	not stated; safety; registry:adverse_events
A2	events	1267 / 6647	not stated; safety; R0009202:Table 3
A2	events	10 / 6647	not stated; safety; registry:adverse_events

Constipation (4 lines; O27D)

Arm	Statistic	Events / N	Detail
A1	events	8 / 6647	not stated; safety; registry:adverse_events
A1	events	836 / 6647	not stated; safety; registry:adverse_events
A2	events	3 / 6647	not stated; safety; registry:adverse_events
A2	events	771 / 6647	not stated; safety; registry:adverse_events

Gallbladder and biliary disease (46 lines; O28)

Arm	Statistic	Events / N	Detail
A1	events	1 / 6647	not stated; safety; porcelain gallbladder; registry:adverse_events
A1	events	11 / 6647	not stated; safety; bile duct stone; registry:adverse_events
A1	events	1 / 6647	not stated; safety; biliary abscess; registry:adverse_events
A1	events	6 / 6647	not stated; safety; biliary colic; registry:adverse_events
A1	events	1 / 6647	not stated; safety; biliary cyst; registry:adverse_events
A1	events	2 / 6647	not stated; safety; biliary obstruction; registry:adverse_events
A1	events	1 / 6647	not stated; safety; biliary tract infection; registry:adverse_events
A1	events	1 / 6647	not stated; safety; cholangitis acute; registry:adverse_events
A1	events	0 / 6647	not stated; safety; cholangitis chronic; registry:adverse_events
A1	events	3 / 6647	not stated; safety; cholangitis; registry:adverse_events
A1	events	0 / 6647	not stated; safety; gallbladder disorder; registry:adverse_events
A1	events	1 / 6647	not stated; safety; gallbladder polyp; registry:adverse_events
A1	events	1 / 6647	not stated; safety; gallbladder rupture; registry:adverse_events
A1	events	0 / 6647	not stated; safety; hydrocholecystis; registry:adverse_events
A1	events	0 / 6647	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A1	events	91 / 6647	not stated; safety; R0009202:Table 3
A1	events	2 / 6647	not stated; safety; acute cholecystitis necrotic; registry:adverse_events
A1	events	56 / 6647	not stated; safety; cholecystitis acute; registry:adverse_events
A1	events	6 / 6647	not stated; safety; cholecystitis chronic; registry:adverse_events
A1	events	3 / 6647	not stated; safety; cholecystitis; registry:adverse_events
A1	events	1 / 6647	not stated; safety; emphysematous cholecystitis; registry:adverse_events
A1	events	158 / 6647	not stated; safety; cholelithiasis; R0009202:Table 3
A1	events	29 / 6647	not stated; safety; cholelithiasis; registry:adverse_events
A2	events	0 / 6647	not stated; safety; biliary obstruction; registry:adverse_events
A2	events	2 / 6647	not stated; safety; cholangitis; registry:adverse_events
A2	events	1 / 6647	not stated; safety; gallbladder disorder; registry:adverse_events
A2	events	0 / 6647	not stated; safety; gallbladder polyp; registry:adverse_events
A2	events	0 / 6647	not stated; safety; gallbladder rupture; registry:adverse_events
A2	events	1 / 6647	not stated; safety; hydrocholecystis; registry:adverse_events
A2	events	1 / 6647	not stated; safety; hyperplastic cholecystopathy; registry:adverse_events
A2	events	0 / 6647	not stated; safety; porcelain gallbladder; registry:adverse_events
A2	events	0 / 6647	not stated; safety; cholangitis acute; registry:adverse_events
A2	events	0 / 6647	not stated; safety; biliary tract infection; registry:adverse_events
A2	events	0 / 6647	not stated; safety; biliary cyst; registry:adverse_events
A2	events	2 / 6647	not stated; safety; biliary colic; registry:adverse_events
A2	events	0 / 6647	not stated; safety; biliary abscess; registry:adverse_events
A2	events	84 / 6647	not stated; safety; R0009202:Table 3
A2	events	6 / 6647	not stated; safety; acute cholecystitis necrotic; registry:adverse_events
A2	events	42 / 6647	not stated; safety; cholecystitis acute; registry:adverse_events
A2	events	2 / 6647	not stated; safety; cholecystitis chronic; registry:adverse_events
A2	events	4 / 6647	not stated; safety; cholecystitis; registry:adverse_events
A2	events	0 / 6647	not stated; safety; emphysematous cholecystitis; registry:adverse_events
A2	events	7 / 6647	not stated; safety; bile duct stone; registry:adverse_events
A2	events	1 / 6647	not stated; safety; cholangitis chronic; registry:adverse_events
A2	events	134 / 6647	not stated; safety; cholelithiasis; R0009202:Table 3
A2	events	25 / 6647	not stated; safety; cholelithiasis; registry:adverse_events

Acute pancreatitis (14 lines; O29)

Arm	Statistic	Events / N	Detail
A1	events	18 / 6647	not stated; safety; registry:adverse_events
A1	events	0 / 6647	not stated; safety; procedural pancreatitis; registry:adverse_events
A1	events	6 / 6647	not stated; safety; obstructive pancreatitis; registry:adverse_events
A1	events	0 / 6647	not stated; safety; pancreatitis necrotising; registry:adverse_events
A1	events	0 / 6647	not stated; safety; pancreatitis relapsing; registry:adverse_events
A1	events	41 / 6647	not stated; safety; pancreatitis; R0009202:Table 3
A1	events	6 / 6647	not stated; safety; pancreatitis; registry:adverse_events
A2	events	1 / 6647	not stated; safety; procedural pancreatitis; registry:adverse_events
A2	events	39 / 6647	not stated; safety; pancreatitis; R0009202:Table 3
A2	events	3 / 6647	not stated; safety; pancreatitis; registry:adverse_events
A2	events	20 / 6647	not stated; safety; registry:adverse_events
A2	events	4 / 6647	not stated; safety; obstructive pancreatitis; registry:adverse_events
A2	events	1 / 6647	not stated; safety; pancreatitis necrotising; registry:adverse_events
A2	events	1 / 6647	not stated; safety; pancreatitis relapsing; registry:adverse_events

Medullary thyroid carcinoma (2 lines; O32A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 6647	not stated; safety; R0009202:Table 3
	A2	events				0 / 6647	not stated; safety; R0009202:Table 3

Thyroid cancer (any) (8 lines; O32B)

Arm	Statistic	Events / N	Detail
A1	events	2 / 6647	not stated; safety; medullary thyroid cancer; R0009202:Table 3
A1	events	6 / 6647	not stated; safety; papillary thyroid cancer; registry:adverse_events
A1	events	0 / 6647	not stated; safety; follicular thyroid cancer; registry:adverse_events
A1	events	9 / 6647	not stated; safety; other thyroid carcinoma; R0009202:Table 3
A2	events	0 / 6647	not stated; safety; medullary thyroid cancer; R0009202:Table 3
A2	events	1 / 6647	not stated; safety; follicular thyroid cancer; registry:adverse_events
A2	events	2 / 6647	not stated; safety; other thyroid carcinoma; R0009202:Table 3
A2	events	1 / 6647	not stated; safety; papillary thyroid cancer; registry:adverse_events

Diabetic retinopathy complications (4 lines; O33)

Arm	Statistic	Events / N	Detail
A1	events	5 / 6647	not stated; safety; vitreous haemorrhage; registry:adverse_events
A1	events	2 / 6647	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	2 / 6647	not stated; safety; diabetic retinopathy; registry:adverse_events
A2	events	4 / 6647	not stated; safety; vitreous haemorrhage; registry:adverse_events

Nonarteritic anterior ischemic optic neuropathy (2 lines; O34)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				1 / 6647	not stated; safety; optic ischaemic neuropathy; registry:adverse_events
	A2	events				1 / 6647	not stated; safety; optic ischaemic neuropathy; registry:adverse_events

Suicidal ideation or behavior (4 lines; O35A)

Arm	Statistic	Events / N	Detail
A1	events	1 / 6647	not stated; safety; suicidal ideation; registry:adverse_events
A1	events	1 / 6647	not stated; safety; suicide attempt; registry:adverse_events
A2	events	2 / 6647	not stated; safety; suicidal ideation; registry:adverse_events
A2	events	3 / 6647	not stated; safety; suicide attempt; registry:adverse_events

Death by suicide (2 lines; O35B)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 6647	not stated; safety; registry:adverse_events
	A2	events				0 / 6647	not stated; safety; registry:adverse_events

Gastroparesis (2 lines; O37A)

Week	Arm	Statistic	Estimate	SE or SD	95% CI	Events / N	Detail
	A1	events				2 / 6647	not stated; safety; diabetic gastroparesis; registry:adverse_events
	A2	events				0 / 6647	not stated; safety; diabetic gastroparesis; registry:adverse_events

Intestinal obstruction or ileus (18 lines; O37B)

Arm	Statistic	Events / N	Detail
A1	events	3 / 6647	not stated; safety; intestinal obstruction; registry:adverse_events
A1	events	0 / 6647	not stated; safety; gallstone ileus; registry:adverse_events
A1	events	1 / 6647	not stated; safety; ileus paralytic; registry:adverse_events
A1	events	3 / 6647	not stated; safety; ileus; registry:adverse_events
A1	events	1 / 6647	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events
A1	events	0 / 6647	not stated; safety; large intestinal obstruction; registry:adverse_events
A1	events	1 / 6647	not stated; safety; mechanical ileus; registry:adverse_events
A1	events	5 / 6647	not stated; safety; small intestinal obstruction; registry:adverse_events
A1	events	4 / 6647	not stated; safety; subileus; registry:adverse_events
A2	events	0 / 6647	not stated; safety; ileus paralytic; registry:adverse_events
A2	events	4 / 6647	not stated; safety; ileus; registry:adverse_events
A2	events	10 / 6647	not stated; safety; intestinal obstruction; registry:adverse_events
A2	events	0 / 6647	not stated; safety; intestinal pseudo-obstruction; registry:adverse_events
A2	events	1 / 6647	not stated; safety; large intestinal obstruction; registry:adverse_events
A2	events	2 / 6647	not stated; safety; gallstone ileus; registry:adverse_events
A2	events	2 / 6647	not stated; safety; mechanical ileus; registry:adverse_events
A2	events	5 / 6647	not stated; safety; small intestinal obstruction; registry:adverse_events
A2	events	0 / 6647	not stated; safety; subileus; registry:adverse_events

Pancreatic cancer (12 lines; O38)

Arm	Statistic	Events / N	Detail
A1	events	2 / 6647	not stated; safety; pancreatic carcinoma stage iv; registry:adverse_events
A1	events	17 / 6647	not stated; safety; R0009202:Table 3
A1	events	4 / 6647	not stated; safety; registry:adverse_events
A1	events	1 / 6647	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A1	events	3 / 6647	not stated; safety; ductal adenocarcinoma of pancreas; registry:adverse_events
A1	events	6 / 6647	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events
A2	events	2 / 6647	not stated; safety; ductal adenocarcinoma of pancreas; registry:adverse_events
A2	events	3 / 6647	not stated; safety; adenocarcinoma pancreas; registry:adverse_events
A2	events	5 / 6647	not stated; safety; registry:adverse_events
A2	events	17 / 6647	not stated; safety; R0009202:Table 3
A2	events	0 / 6647	not stated; safety; pancreatic carcinoma stage iv; registry:adverse_events
A2	events	5 / 6647	not stated; safety; pancreatic carcinoma metastatic; registry:adverse_events