Primary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| 10 mg Tirzepatide | -2.43 | 0.053 |
| 15 mg Tirzepatide | -2.58 | 0.053 |
| Insulin Glargine | -1.44 | 0.030 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataA Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk
Short name SURPASS-4
NCTNCT03730662 (opens ClinicalTrials.gov in a new tab)Other id17072Other idI8F-MC-GPGMOther id2018-002618-11Other id2018
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 2,002 participants (actual)
- Sponsor
- Eli Lilly and Company · Industry
- Design
- Randomized · Open label (no masking)
- Countries
15 countries
United States, Argentina, Australia, Brazil, Canada, Greece, Israel, Mexico, Poland, Puerto Rico, Romania, Russia, Slovakia, Spain, Taiwan
- Start
- 20 Nov 2018
- Primary completion
- 22 Jan 2021
- Completion
- 22 Apr 2021
- First posted
- 5 Nov 2018
- Last update posted
- 14 Feb 2022
- Conditions
- Type 2 Diabetes Mellitus
Timeline
1 trial · 1 completed · 1 with posted results
- Completed
- Ongoing
- Not yet recruiting
- Stopped
- Estimated dates (est.)
- Results posted
20182019202020212022
- Ph 3
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The purpose of the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.
Interventions
- TirzepatideDrug
- Insulin GlargineDrug
Arms4
Experimental
5 mg Tirzepatide
5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.
Experimental
10 mg Tirzepatide
10 mg tirzepatide administered SC once a week.
Experimental
15 mg Tirzepatide
15 mg tirzepatide administered SC once a week.
Active comparator
Insulin Glargine
Insulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG \<100 mg/dL, following a treat-to-target (TTT) algorithm.
Primary outcomes1
Outcomes the sponsor listed as primary.
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
Time frame · Baseline, Week 52
Registry description
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline sodium-glucose co-transporter-2 inhibitor (SGLT-2i) use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Secondary outcomes(7)
Change From Baseline in HbA1c (5 mg)
Time frame · Baseline, Week 52
Registry description
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Change From Baseline in Body Weight
Time frame · Baseline, Week 52
Registry description
LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants With HbA1c of <7.0%
Time frame · Week 52
Registry description
HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Change From Baseline in Fasting Serum Glucose
Time frame · Baseline, Week 52
Registry description
LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
Time frame · Baseline, Week 52
Registry description
The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. LS mean was determined by mixed-model repeated measures (MMRM) model with variables Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline SGLT-2i use Flag (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
Time frame · 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35
Registry description
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
Time frame · Baseline through Week 52
Registry description
The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL (\<3.0 mmol/L) or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Post-baseline comparisons between treatment and control group was evaluated using negative binomial model with variables : Number of episodes = Baseline HbA1c Group (\<=8.5%, \>8.5%) + Pooled Country + Baseline SGLT-2i use Flag (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable
Posted results
Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.
Primary outcome results
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in HbA1c (5 mg)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -2.24 | 0.053 |
| Insulin Glargine | -1.44 | 0.030 |
Secondary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in Body Weight
| Group | Value (Kilograms (kg)) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -7.1 | 0.34 |
| 10 mg Tirzepatide | -9.5 | 0.34 |
| 15 mg Tirzepatide | -11.7 | 0.33 |
| Insulin Glargine | 1.9 | 0.19 |
Secondary outcomeNumber· Week 52
Percentage of Participants With HbA1c of <7.0%
| Group | Value (percentage of participants) |
|---|---|
| 5 mg Tirzepatide | 80.98 |
| 10 mg Tirzepatide | 88.16 |
| 15 mg Tirzepatide | 90.72 |
| Insulin Glargine | 50.72 |
Secondary outcomeLeast squares mean· Baseline, Week 52
Change From Baseline in Fasting Serum Glucose
| Group | Value (milligram per Deciliter (mg/dL)) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -50.4 | 2.07 |
| 10 mg Tirzepatide | -54.9 | 2.06 |
| 15 mg Tirzepatide | -59.3 | 2.04 |
| Insulin Glargine | -51.4 | 1.17 |
Secondary outcomeLeast squares mean· Baseline, Week 52
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
| Group | Value (mg/dL) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -58.4 | 1.65 |
| 10 mg Tirzepatide | -61.1 | 1.66 |
| 15 mg Tirzepatide | -66.1 | 1.66 |
| Insulin Glargine | -46.1 | 0.96 |
Secondary outcomeGeometric mean· 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
| Group | Value (Nanograms per millilitre per hour) | Spread |
|---|---|---|
| 5 mg Tirzepatide | 81800 | 23.9 |
| 10 mg Tirzepatide | 165000 | 20.3 |
| 15 mg Tirzepatide | 246000 | 20.6 |
Secondary outcomeMean· Baseline through Week 52
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
| Group | Value (Episodes/participant/365.25 days) | Spread |
|---|---|---|
| 5 mg Tirzepatide | 0.10 | 0.023 |
| 10 mg Tirzepatide | 0.09 | 0.025 |
| 15 mg Tirzepatide | 0.11 | 0.030 |
| Insulin Glargine | 0.35 | 0.044 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| 5 mg Tirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week. | 15 / 329 | 48 / 329 | 112 / 329 |
| 10 mg Tirzepatide10 mg tirzepatide administered SC once a week. | 2 / 328 | 54 / 328 | 158 / 328 |
| 15 mg Tirzepatide15 mg tirzepatide administered SC once a week. | 8 / 338 | 41 / 338 | 184 / 338 |
| Insulin GlargineInsulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets. The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG \<100 mg/dL, following a treat-to-target (TTT) algorithm. | 35 / 1000 | 193 / 1000 | 192 / 1000 |
Each cell reads participants affected / participants at risk, as the registry posted them.
Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works
Studies6
Studies that cite this trial.
Studies with results
3 studies on this page
Indexing hint: Meta-analysis (pooled) · 2022
4 results
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.
Sattar et al. 2022Nature medicinecited by 268
PMID 35210595PMC8938269DOI 10.1038/s41591-022-01707-4PUB-35210595
CC BY4 results
Indexing hint: Randomized controlled trial · 2022
4 results
Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial.
Heerspink et al. 2022The lancet. Diabetes & endocrinologycited by 233
PMID 36152639DOI 10.1016/s2213-8587(22)00243-1PUB-36152639
Full text at the publisher4 results
Indexing hint: Clinical trial · 2021
12 results
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 et al. 2021Lancet (London, England)cited by 533
PMID 34672967DOI 10.1016/s0140-6736(21)02188-7PUB-34672967
Full text at the publisher12 results
More studies
3 studies on this page
PubMed tag: none · 2025
Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics.
De Block et al. 2025Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 13
PMID 39531161PMC11759727DOI 10.1007/s13300-024-01660-0PUB-39531161
Free to read · publisher termsCC BY-NC
PubMed tag: none · 2023
Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme.
Boye et al. 2023Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 16
PMID 37526908PMC10570242DOI 10.1007/s13300-023-01451-zPUB-37526908
Free to read · publisher termsCC BY-NC
PubMed tag: none · 2023
Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.
Boye et al. 2023Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 5
PMID 37668888PMC10570229DOI 10.1007/s13300-023-01457-7PUB-37668888
Free to read · publisher termsCC BY-NC
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
Participants must:
* Have been diagnosed with type 2 diabetes mellitus (T2DM)
* Have HbA1c between ≥7.5% and ≤10.5%
* Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
* Have increased risk for cardiovascular (CV) events
* Be of stable weight (± 5%)
* Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening
Exclusion Criteria
Participants must not:
* Have type 1 diabetes mellitus
* Have had chronic or acute pancreatitis any time prior to study entry
* Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring immediate or urgent treatment
* Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss
* Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) enzyme level \>3.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory. Participants with nonalcoholic fatty liver disease (NAFLD) are eligible for participation in this trial only if there ALT level is ≤3.0 the ULN for the reference range
* Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months
* Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
* Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 3 months
* Have been taking weight loss drugs, including over-the-counter medications during the last 3 months
PepBank is a research reference. Talk to a doctor before you use any peptide.