Primary outcomeLeast squares mean· Baseline, Week 40
Change From Baseline in Hemoglobin A1c (HbA1c)
| Group | Value (Percentage of HbA1c) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -1.87 | 0.094 |
| 10 mg Tirzepatide | -1.89 | 0.096 |
| 15 mg Tirzepatide | -2.07 | 0.098 |
| Placebo | 0.04 | 0.105 |
Trial · Interventional
CompletedPhase 3Results postedRegistry dataA Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone
Short name SURPASS-1
Overview
- Status
- Completed
- Phase
- Phase 3
- Enrollment
- 478 participants (actual)
- Sponsor
- Eli Lilly and Company · Industry
- Design
- Randomized · Double masking
- Countries
5 countries
United States, India, Japan, Mexico, Puerto Rico
- Start
- 3 Jun 2019
- Primary completion
- 5 Oct 2020
- Completion
- 28 Oct 2020
- First posted
- 17 May 2019
- Last update posted
- 20 Oct 2021
- 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
201920202021
- Ph 3
Registry summary
Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.
The goal for this study is to evaluate the efficacy and safety of tirzepatide versus placebo in participants with type 2 diabetes not under control with diet and exercise alone. The study will last approximately 47 weeks and may include about 15 visits.
Interventions
- TirzepatideDrug
- PlaceboDrug
Arms4
Experimental
5 mg Tirzepatide
Participants received 5 milligrams (mg) of tirzepatide as subcutaneous injection once a week.
Experimental
10 mg Tirzepatide
Participants received 10mg of tirzepatide as subcutaneous injection once a week.
Experimental
15 mg Tirzepatide
Participants received 15mg of tirzepatide as subcutaneous injection once a week.
Placebo comparator
Placebo
Participants received placebo as subcutaneous injection once a week.
Primary outcomes1
Outcomes the sponsor listed as primary.
Change From Baseline in Hemoglobin A1c (HbA1c)
Time frame · Baseline, Week 40
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 with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Secondary outcomes(8)
Change From Baseline in Body Weight
Time frame · Baseline, Week 40
Registry description
Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants With HbA1c Target Value of <7%
Time frame · Week 40
Registry description
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Change From Baseline in Fasting Serum Glucose
Time frame · Baseline, Week 40
Registry description
Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants With HbA1c Target Value of <5.7%
Time frame · Week 40
Registry description
Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
Time frame · Baseline, Week 40
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. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Who Achieved Weight Loss ≥5%
Time frame · Week 40
Registry description
Percentage of Participants who Achieved Weight Loss ≥5%.
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia
Time frame · Baseline through end of safety follow-up (up to week 44)
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. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide
Time frame · Week 7, 15 and 23
Registry description
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.
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 40
Change From Baseline in Body Weight
| Group | Value (Kilograms (kg)) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -7.0 | 0.52 |
| 10 mg Tirzepatide | -7.8 | 0.53 |
| 15 mg Tirzepatide | -9.5 | 0.54 |
| Placebo | -0.7 | 0.57 |
Secondary outcomeNumber· Week 40
Percentage of Participants With HbA1c Target Value of <7%
| Group | Value (Percentage of participants) |
|---|---|
| 5 mg Tirzepatide | 86.78 |
| 10 mg Tirzepatide | 91.53 |
| 15 mg Tirzepatide | 87.93 |
| Placebo | 19.64 |
Secondary outcomeLeast squares mean· Baseline, Week 40
Change From Baseline in Fasting Serum Glucose
| Group | Value (milligram per Deciliter (mg/dL)) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -43.6 | 3.40 |
| 10 mg Tirzepatide | -45.9 | 3.45 |
| 15 mg Tirzepatide | -49.3 | 3.62 |
| Placebo | 12.9 | 4.00 |
Secondary outcomeNumber· Week 40
Percentage of Participants With HbA1c Target Value of <5.7%
| Group | Value (Percentage of participants) |
|---|---|
| 5 mg Tirzepatide | 33.88 |
| 10 mg Tirzepatide | 30.51 |
| 15 mg Tirzepatide | 51.72 |
| Placebo | 0.89 |
Secondary outcomeLeast squares mean· Baseline, Week 40
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
| Group | Value (mg/dL) | Spread |
|---|---|---|
| 5 mg Tirzepatide | -46.9 | 2.09 |
| 10 mg Tirzepatide | -47.9 | 2.11 |
| 15 mg Tirzepatide | -45.7 | 2.23 |
| Placebo | -9.2 | 2.53 |
Secondary outcomeNumber· Week 40
Percentage of Participants Who Achieved Weight Loss ≥5%
| Group | Value (Percentage of participants) |
|---|---|
| 5 mg Tirzepatide | 66.94 |
| 10 mg Tirzepatide | 77.97 |
| 15 mg Tirzepatide | 76.72 |
| Placebo | 14.29 |
Secondary outcomeMean· Baseline through end of safety follow-up (up to week 44)
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 | 0.02 | 0.002 |
| 10 mg Tirzepatide | 0.02 | 0.002 |
| 15 mg Tirzepatide | 0.02 | 0.002 |
| Placebo | 0.04 | 0.028 |
Adverse events, as posted
| Group | Deaths | Serious events | Other events |
|---|---|---|---|
| 5 mg TirzepatideParticipants received 5 mg of Tirzepatide as subcutaneous injection, once weekly. | 0 / 121 | 5 / 121 | 50 / 121 |
| 10 mg TirzepatideParticipants received 10 mg of Tirzepatide as subcutaneous injection, once weekly. | 0 / 121 | 2 / 121 | 55 / 121 |
| 15 mg TirzepatideParticipants received 15 mg of Tirzepatide as subcutaneous injection, once weekly. | 0 / 121 | 1 / 121 | 53 / 121 |
| PlaceboParticipants received placebo as subcutaneous injection, once weekly. | 1 / 115 | 3 / 115 | 54 / 115 |
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
Studies5
Studies that cite this trial.
Studies with results
1 study 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
More studies
4 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
Indexing hint: Randomized controlled trial · 2021
Corrected
Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial.
Rosenstock et al. 2021Lancet (London, England)cited by 789
PMID 34186022DOI 10.1016/s0140-6736(21)01324-6PUB-34186022
Full text at the publisher
Eligibility
Who could join, as posted.
- Sex
- All
- Age
- from 18 Years
- Healthy volunteers
- Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria:
* Have been diagnosed with type 2 diabetes mellitus (T2DM).
* Are naïve to diabetes injectable therapies and have not used any oral antihyperglycemic medications (OAMs) during the 3 months preceding screening.
* Have HbA1c between ≥7.0% and ≤9.5%.
* Be of stable weight (± 5%) for at least 3 months before screening.
* Have a BMI ≥23 kilograms per meter squared (kg/m²) at screening.
Exclusion Criteria:
* 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 acute treatment.
* Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.
* Have an estimated glomerular filtration rate \<30 mL/minute/1.73 m².
* 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 weight loss drugs, including over-the-counter medications during the last 3 months.
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