Skip to content

Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Tirzepatide (LY3298176) Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Participants With Type 2 Diabetes

Short name SURPASS-2

NCTNCT03987919 (opens ClinicalTrials.gov in a new tab)Other id17001Other idI8F-MC-GPGLOther id2018-004422-29Other id2018
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
1,879 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
9 countries

United States, Argentina, Australia, Brazil, Canada, Israel, Mexico, Puerto Rico, United Kingdom

Start
30 Jul 2019
Primary completion
28 Jan 2021
Completion
15 Feb 2021
First posted
17 Jun 2019
Last update posted
14 Feb 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-2

    NCT03987919

    30 Jul 2019 to 15 Feb 2021

Registry summary

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

The reason for this study is to compare the effect of the study drug tirzepatide to semaglutide on blood sugar levels in participants with type 2 diabetes. The study will last approximately 47 weeks and may include about 12 visits.

Interventions

  • TirzepatideDrug
  • SemaglutideDrug

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

    1 mg Semaglutide

    1 mg semaglutide 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 + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary outcomes(9)

  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 + 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 + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + 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 (FSG)

    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%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

  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 + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (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. Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

    Time frame · Baseline, Week 40

    Registry description

    DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. The questionnaire consists of 8 items, 6 of which (1 and 4 through 8) assess treatment satisfaction. Each item is rated on a 7-point Likert scale. The scores from the 6 treatment satisfaction items are summed to a Total Treatment Satisfaction Score, which ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS Mean was determined by ANCOVA with Baseline DTSQs + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

  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 HbA1c Group (\<=8.5%, \>8.5%) + Treatment.

  9. Percentage of Participants Achieving an HbA1c Target Value of <5.7%

    Time frame · Week 40

    Registry description

    Percentage of Participants Achieving an HbA1c Target Value of \<5.7%.

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-2.370.048
15 mg Tirzepatide-2.460.048
1 mg Semaglutide-1.860.048
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-2.090.047
1 mg Semaglutide-1.860.048
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Body Weight

GroupValue (Kilograms (kg))Spread
5 mg Tirzepatide-7.80.33
10 mg Tirzepatide-10.30.34
15 mg Tirzepatide-12.40.34
1 mg Semaglutide-6.20.33
Secondary outcomeNumber· Week 40

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

GroupValue (Percentage of Participants)
5 mg Tirzepatide85.47
10 mg Tirzepatide88.89
15 mg Tirzepatide92.24
1 mg Semaglutide81.13
Secondary outcomeLeast squares mean· Baseline, Week 40

Change From Baseline in Fasting Serum Glucose (FSG)

GroupValue (milligram per Deciliter (mg/dL))Spread
5 mg Tirzepatide-56.01.57
10 mg Tirzepatide-61.61.60
15 mg Tirzepatide-63.41.59
1 mg Semaglutide-48.61.58
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-65.41.04
10 mg Tirzepatide-70.61.05
15 mg Tirzepatide-74.31.05
1 mg Semaglutide-61.41.04
Secondary outcomeNumber· Week 40

Percentage of Participants Who Achieved Weight Loss ≥5%

GroupValue (Percentage of Participants)
5 mg Tirzepatide68.55
10 mg Tirzepatide82.35
15 mg Tirzepatide86.21
1 mg Semaglutide58.44
Secondary outcomeLeast squares mean· Baseline, Week 40

Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Total Score

GroupValue (Units on a Scale)Spread
5 mg Tirzepatide-1.30.10
10 mg Tirzepatide-1.40.10
15 mg Tirzepatide-1.50.10
1 mg Semaglutide-1.10.10

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg Tirzepatide5 mg tirzepatide administered subcutaneously (SC) once a week.4 / 47033 / 470170 / 470
10 mg Tirzepatide10 mg tirzepatide administered SC once a week.4 / 46925 / 469187 / 469
15 mg Tirzepatide15 mg tirzepatide administered SC once a week.4 / 47027 / 470202 / 470
1 mg Semaglutide1 mg of semaglutide administered SC once a week.1 / 46913 / 469172 / 469

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

Studies8

Studies that cite this trial.

Studies with results

3 studies on this page

Indexing hint: Randomized controlled trial · 2024

9 results

Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison.

Osumili et al. 2024Diabetes research and clinical practicecited by 2

PMID 38777128DOI 10.1016/j.diabres.2024.111717PUB-38777128

Full text at the publisher9 results
Publisher pageSee results (9)

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)

Indexing hint: Randomized controlled trial · 2021

19 results

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.

Frías et al. 2021The New England journal of medicinecited by 1,535

PMID 34170647DOI 10.1056/nejmoa2107519PUB-34170647

Full text at the publisher19 results
Publisher pageSee results (19)

More studies

5 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
Read at source

PubMed tag: none · 2023

Time to Reach Glycaemic and Body Weight Loss Thresholds with Tirzepatide in Patients with Type 2 Diabetes: A Pre-planned Exploratory Analysis of SURPASS-2 and SURPASS-3.

Viljoen et al. 2023Diabetes therapy : research, treatment and education of diabetes and related disorderscited by 7

PMID 37000390PMC10126190DOI 10.1007/s13300-023-01398-1PUB-37000390

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

PubMed tag: none · 2023

Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates.

Reitzel et al. 2023Current medical research and opinioncited by 1

PMID 37415503DOI 10.1080/03007995.2023.2231275PUB-37415503

Full text at the publisher
Publisher page

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

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedTen Doesschate T, van der Vaart TW, Debisarun PA, Taks E, Moorlag SJCFM, Paternotte N, Boersma WG, Kuiper VP, Roukens AHE, Rijnders BJA, Voss A, Veerman KM, Kerckhoffs APM, Oever JT, van Crevel R, van Nieuwkoop C, Lalmohamed A, van de Wijgert JHHM, Netea MG, Bonten MJM, van Werkhoven CH. Bacillus Calmette-Guerin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial. Clin Microbiol Infect. 2022 Sep;28(9):1278-1285. doi: 10.1016/j.cmi.2022.04.009. Epub 2022 Apr 28. PMID 35489606

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) * Have HbA1c between ≥7.0% and ≤10.5% * Be on stable treatment with unchanged dose of metformin \>1500 mg/day for at least 3 months prior to screening * Be of stable weight (±5%) for at least 3 months before screening * Have a body mass index (BMI) ≥25 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 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 an estimated glomerular filtration rate \<45 milliliters/minute/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 any other diabetes medicines other than metformin 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.