Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ

Lancet (London, England)18 Oct 2021Cited by 533 (Europe PMC)

PMID34672967DOI10.1016/s0140-6736(21)02188-7PepBankPUB-34672967

Publisher page PubMedAsk about this study

Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and high cardiovascular risk, tirzepatide 15 mg lowered HbA1c by 2·58% at 52 weeks, versus 1·44% with insulin glargine.
In plain wordsIn adults with type 2 diabetes and high heart risk, tirzepatide 15 mg lowered HbA1c more than insulin glargine at 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c change at week 52, 15 mg
Study
n = 338
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 52 weeksAs given in this study (human).
Measurements
HbA1c change
−2.58%
tirzepatide 15 mg
HbA1c change
−1.44%
glargine
Source sentences
Summary
At 52 weeks, mean HbA_1c changes with tirzepatide were -2·43% (SD 0·05) with 10 mg and -2·58% (0·05) with 15 mg, versus -1·44% (0·03) with glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296702
02HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and high cardiovascular risk, tirzepatide 10 mg lowered HbA1c by 2·43% at 52 weeks, versus 1·44% with insulin glargine.
In plain wordsIn adults with type 2 diabetes and high heart risk, tirzepatide 10 mg lowered HbA1c more than insulin glargine at 52 weeks.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c change at week 52, 10 mg
Study
n = 328
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg once weekly · subcutaneous · 52 weeksAs given in this study (human).
Measurements
HbA1c change
−2.43%
tirzepatide 10 mg
HbA1c change
−1.44%
glargine
Source sentences
Summary
At 52 weeks, mean HbA_1c changes with tirzepatide were -2·43% (SD 0·05) with 10 mg and -2·58% (0·05) with 15 mg, versus -1·44% (0·03) with glargine.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296701
03HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and high cardiovascular risk, the HbA1c difference between tirzepatide 10 mg and glargine was -0·99%, and the non-inferiority margin of 0·3% was met.
In plain wordsIn adults with type 2 diabetes and high heart risk, tirzepatide 10 mg lowered HbA1c more than glargine, and met the non-inferiority test.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c treatment difference versus glargine, 10 mg (non-inferiority)
Study
n: not reported in source
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
10 mg once weekly · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−0.99%
tirzepatide 10 mg vs glargine
Source sentences
Summary
The estimated treatment difference versus glargine was -0·99% (multiplicity adjusted 97·5% CI -1·13 to -0·86) for tirzepatide 10 mg and -1·14% (-1·28 to -1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296703
04HumanRandomized controlled trialEfficacy outcome
In adults with type 2 diabetes and high cardiovascular risk, the HbA1c difference between tirzepatide 15 mg and glargine was -1·14%, and the non-inferiority margin of 0·3% was met.
In plain wordsIn adults with type 2 diabetes and high heart risk, tirzepatide 15 mg lowered HbA1c more than glargine, and met the non-inferiority test.
Peptide
Tirzepatide
Outcome
DecreaseHbA1c treatment difference versus glargine, 15 mg (non-inferiority)
Study
n: not reported in source
Comparator
Insulin glargine
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
15 mg once weekly · subcutaneous · 52 weeksAs given in this study (human).
Measurements
Estimated treatment difference
−1.14%
tirzepatide 15 mg vs glargine
Source sentences
Summary
The estimated treatment difference versus glargine was -0·99% (multiplicity adjusted 97·5% CI -1·13 to -0·86) for tirzepatide 10 mg and -1·14% (-1·28 to -1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296704
05HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, major cardiovascular events (MACE-4) were not increased with tirzepatide compared with glargine (hazard ratio 0·74).
In plain wordsIn adults with type 2 diabetes and high heart risk, tirzepatide did not raise the rate of major heart events compared with insulin glargine.
Peptide
Tirzepatide
Outcome
No significant changeAdjudicated MACE-4
Study
n = 1,995
Comparator
Insulin glargine
Outcome group
Cardiovascular events · Cardiovascular
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Hazard ratio
0.74
MACE-4, tirzepatide vs glargine
Source sentences
Summary
Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51-1·08).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296711
06HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, 25 deaths occurred with tirzepatide and 35 with glargine; no test was reported.
In plain wordsIn adults with type 2 diabetes and high heart risk, 25 deaths occurred with tirzepatide and 35 with insulin glargine.
Peptide
Tirzepatide
Outcome
Direction not reportedDeaths during the study
Study
n = 1,995
Comparator
Insulin glargine
Outcome group
Mortality · Whole body
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Deaths
25 n
tirzepatide
Deaths
35 n
glargine
Source sentences
Summary
60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296712
07HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, nausea was more frequent with tirzepatide (12-23%) than with glargine (2%).
In plain wordsIn adults with type 2 diabetes and high heart risk, nausea was more common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
IncreaseNausea
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Nausea incidence
12 to 23%
tirzepatide
Nausea incidence
2%
glargine
Source sentences
Summary
Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296705
08HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, diarrhoea was more frequent with tirzepatide (13-22%) than with glargine (4%).
In plain wordsIn adults with type 2 diabetes and high heart risk, diarrhoea was more common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
IncreaseDiarrhoea
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Diarrhoea incidence
13 to 22%
tirzepatide
Diarrhoea incidence
4%
glargine
Source sentences
Summary
Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296706
09HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, decreased appetite was more frequent with tirzepatide (9-11%) than with glargine (below 1%).
In plain wordsIn adults with type 2 diabetes and high heart risk, decreased appetite was more common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
IncreaseDecreased appetite
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Decreased appetite incidence
9 to 11%
tirzepatide
Decreased appetite incidence
< 1%
glargine
Source sentences
Summary
Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296707
10HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, vomiting was more frequent with tirzepatide (5-9%) than with glargine (2%).
In plain wordsIn adults with type 2 diabetes and high heart risk, vomiting was more common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
IncreaseVomiting
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Vomiting incidence
5 to 9%
tirzepatide
Vomiting incidence
2%
glargine
Source sentences
Summary
Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase.
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296708
11HumanRandomized controlled trialSafety outcome
In adults with type 2 diabetes and high cardiovascular risk, hypoglycaemia occurred in fewer participants with tirzepatide (6-9%) than with glargine (19%).
In plain wordsIn adults with type 2 diabetes and high heart risk, low blood sugar was less common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
DecreaseHypoglycaemia (glucose <54 mg/dL or severe)
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Hypoglycaemia incidence
6 to 9%
tirzepatide
Hypoglycaemia incidence
19%
glargine
Source sentences
Summary
The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6-9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1-3% vs glargine 16%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296709
12HumanRandomized controlled trialSafety outcome
In participants not on sulfonylureas, hypoglycaemia occurred in 1-3% with tirzepatide versus 16% with glargine.
In plain wordsIn people with type 2 diabetes not taking sulfonylureas, low blood sugar was less common with tirzepatide than with insulin glargine.
Peptide
Tirzepatide
Outcome
DecreaseHypoglycaemia in participants not on sulfonylureas
Study
n: not reported in source
Comparator
Insulin glargine
Outcome group
Adverse events · Metabolic and weight
Studied dose
5, 10 or 15 mg once weekly · subcutaneous · 52 to 104 weeksAs given in this study (human).
Measurements
Hypoglycaemia incidence
1 to 3%
tirzepatide, not on sulfonylureas
Hypoglycaemia incidence
16%
glargine, not on sulfonylureas
Source sentences
Summary
The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6-9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1-3% vs glargine 16%).
2 context sentences(design, population, supporting numbers)
Summary · context
Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA_1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m² or greate…
Summary · context
Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL.
Report a problemFND-3467296710

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · 1 with posted results · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 3Results postedNCT03730662

A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk

Eli Lilly and Companyn = 2,00220 Nov 2018 to 22 Apr 2021

Type 2 Diabetes Mellitus

Trial page ClinicalTrials.govUpdated 14 Feb 2022

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

Subjects

Terms as the source lists them.

Publication types

MeSH terms

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