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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Tirzepatide (LY3298176) Versus Placebo in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Short name SURPASS-5

NCTNCT04039503 (opens ClinicalTrials.gov in a new tab)Other id16998Other idI8F-MC-GPGIOther id2019-000860-99Other id2019
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
475 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
8 countries

United States, Czechia, Germany, Japan, Poland, Puerto Rico, Slovakia, Spain

Start
30 Aug 2019
Primary completion
22 Dec 2020
Completion
13 Jan 2021
First posted
31 Jul 2019
Last update posted
12 Jan 2022
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2019202020212022
  1. Ph 3

    SURPASS-5

    NCT04039503

    30 Aug 2019 to 13 Jan 2021

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to placebo in participants with type 2 diabetes that are already on insulin glargine, with or without metformin. Participants will administer tirzepatide or placebo along with their previous glucose lowering medications. The study will last approximately 47 weeks and may include about 23 visits.

Interventions

  • TirzepatideDrug
  • PlaceboDrug

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.

  • Placebo comparator

    Placebo

    Placebo administered SC once a week.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

    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 + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary outcomes(10)

  1. Change From Baseline in HbA1c (5 mg)

    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 + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

  2. 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 + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

  3. Percentage of Participants Achieving an 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.

  4. 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. LS Mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

  5. 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 + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment (Type III sum of squares).

  6. Percentage of Participants Who Achieved Weight Loss ≥5%

    Time frame · Week 40

    Registry description

    Percentage of Participants who Achieved Weight Loss ≥5%.

  7. Percentage Change From Baseline in Daily Mean Insulin Glargine Dose

    Time frame · Baseline, Week 40

    Registry description

    LS mean was calculated using MMRM model with log (Baseline) + Baseline Metformin Use (Yes, No) + Pooled Country + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

  8. Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe Hypoglycemia

    Time frame · Baseline through 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 Metformin Use (Yes, No) + Baseline HbA1c Group (\<= 8.0%, \>8.0%) + Treatment, with log (exposure in days/365.25) as an offset variable.

  9. Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide

    Time frame · Week 7, 15, 23 and 39 post dose

    Registry description

    AUC is a combined measure obtained from Week 7, 15, 23 and 39 and a single averaged measure of AUC was reported.

  10. Percentage of Participants Achieving an 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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)

GroupValue (Percentage of HbA1c)Spread
10 mg Tirzepatide-2.590.081
15 mg Tirzepatide-2.590.083
Placebo-0.930.079
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in HbA1c (5 mg)

GroupValue (Percentage of HbA1c)Spread
5 mg Tirzepatide-2.230.081
Placebo-0.930.079
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Body Weight

GroupValue (Kilograms (kg))Spread
5 mg Tirzepatide-6.20.58
10 mg Tirzepatide-8.20.58
15 mg Tirzepatide-10.90.59
Placebo1.70.57
Secondary outcomeNumber· Week 40

Percentage of Participants Achieving an HbA1c Target Value of <7%

GroupValue (Percentage of Participants)
5 mg Tirzepatide93.04
10 mg Tirzepatide97.35
15 mg Tirzepatide94.02
Placebo33.90
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Fasting Serum Glucose

GroupValue (milligram per Deciliter (mg/dL))Spread
5 mg Tirzepatide-61.42.55
10 mg Tirzepatide-67.92.55
15 mg Tirzepatide-67.72.64
Placebo-38.92.49
Secondary outcomeLeast squares mean· Baseline, Week 40

Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values

GroupValue (mg/dL)Spread
5 mg Tirzepatide-67.12.05
10 mg Tirzepatide-71.72.04
15 mg Tirzepatide-73.72.10
Placebo-39.42.07
Secondary outcomeNumber· Week 40

Percentage of Participants Who Achieved Weight Loss ≥5%

GroupValue (Percentage of Participants)
5 mg Tirzepatide53.91
10 mg Tirzepatide64.60
15 mg Tirzepatide84.62
Placebo5.93
Secondary outcomeLeast squares mean· Baseline, Week 40

Percentage Change From Baseline in Daily Mean Insulin Glargine Dose

GroupValue (International Units (IU))Spread
5 mg Tirzepatide13.07.34
10 mg Tirzepatide8.17.03
15 mg Tirzepatide-11.45.85
Placebo75.011.11

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg Tirzepatide5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.0 / 1169 / 11652 / 116
10 mg Tirzepatide10 mg tirzepatide administered SC once a week.0 / 11913 / 11960 / 119
15 mg Tirzepatide15 mg tirzepatide administered SC once a week.0 / 1209 / 12067 / 120
PlaceboPlacebo administered SC once a week.0 / 12010 / 12058 / 120

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

2 studies on this page

Indexing hint: Randomized controlled trial · 2022

6 results

Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.

Dahl et al. 2022JAMAcited by 475

PMID 35133415PMC8826179DOI 10.1001/jama.2022.0078PUB-35133415

Rights unknown6 results
Source linkSee results (6)

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
Download PDFSee results (4)

More studies

4 studies on this page

PubMed tag: none · 2026

Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.

Bajaj et al. 2026Diabetes therapy : research, treatment and education of diabetes and related disorders

PMID 41961454PMC13156352DOI 10.1007/s13300-026-01859-3PUB-41961454

Free to read · publisher termsCC BY-NC
Read at source

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
Read at source

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
Read at source

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
Read at source

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) and have been treated with insulin glargine (U100), once daily with or without metformin ≥3 months prior to screening visit. * Have HbA1c between ≥7.0% and ≤10.5%. * Have a stable weight (± 5%) for at least 3 months before screening. * Have a body mass index (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 \[for participants on metformin, estimated glomerular filtration rate \<45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)\] * 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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