SURPASS-2

CompletedPhase 3Results posted

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

A Phase 3, Randomized, Open-Label Trial Comparing Efficacy and Safety of Tirzepatide Versus Semaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes

Lead sponsor

Eli Lilly and Company

Assets

GLP-1 / incretin class catch-all / Semaglutide / Tirzepatide

Listed sites

127

Recruiting sites

—

Enrollment

1,879

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥25•HbA1c 7-10.5%

Primary endpoint

•HbA1c, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03987919

Org study ID17001

Secondary ID2018-004422-29

Secondary IDI8F-MC-GPGLEli Lilly and Company

Timeline

Milestones

Study first posted2019-06-17actual

Study start2019-07-30actual

Primary completion2021-01-28actual

Study completion2021-02-15actual

Last update posted2022-02-14actual

Results first posted2022-02-14actual

Assets

Investigational agents

GLP-1 / incretin class catch-all Semaglutide Tirzepatide

Study populations

Who this study enrolls

Type 2 diabetes

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

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

Endpoints (20)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Glycemic / diabetes

Weight & body composition

Patient-reported / QoL

Safety / tolerability / PK

Weight & body composition

4 endpoints

Secondary/registry result

Change From Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Kilograms (kg)	95% CI
5 mg Tirzepatide	-7.8	—
10 mg Tirzepatide	-10.3	—
15 mg Tirzepatide	-12.4	—
1 mg Semaglutide	-6.2	—

LS Mean Difference-1.795% CI-2.6 – -0.7p<0.001Mixed Models Analysis

LS Mean Difference-4.195% CI-5.0 – -3.2p<0.001Mixed Models Analysis

LS Mean Difference-6.295% CI-7.1 – -5.3p<0.001Mixed Models Analysis

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss ≥5%

Time frame:Week 40

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	95% CI
5 mg Tirzepatide	68.55	—
10 mg Tirzepatide	82.35	—
15 mg Tirzepatide	86.21	—
1 mg Semaglutide	58.44	—

Odds Ratio (OR)1.5895% CI1.20 – 2.08p0.001Regression, Logistic

Odds Ratio (OR)3.4995% CI2.57 – 4.75p<0.001Regression, Logistic

Odds Ratio (OR)4.6095% CI3.32 – 6.38p<0.001Regression, Logistic

Secondary/protocol endpoint

Change From Baseline in Body Weight

Time frame:Baseline, Week 40

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss ≥5%

Time frame:Week 40

≥5% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

12 endpoints

Primary/registry result

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

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), Percentage of HbA1c	95% CI
10 mg Tirzepatide	-2.37	—
15 mg Tirzepatide	-2.46	—
1 mg Semaglutide	-1.86	—

LS Mean Difference-0.5195% CI-0.64 – -0.38p<0.001Mixed Models Analysis

LS Mean Difference-0.6095% CI-0.73 – -0.47p<0.001Mixed Models Analysis

Primary/protocol endpoint

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

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change From Baseline in HbA1c (5 mg)

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), Percentage of HbA1c	95% CI
5 mg Tirzepatide	-2.09	—
1 mg Semaglutide	-1.86	—

LS Mean Difference-0.2395% CI-0.36 – -0.10p<0.001Mixed Models Analysis

Secondary/registry result

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

Time frame:Week 40

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
5 mg Tirzepatide	85.47	—
10 mg Tirzepatide	88.89	—
15 mg Tirzepatide	92.24	—
1 mg Semaglutide	81.13	—

Odds Ratio (OR)1.5495% CI1.06 – 2.23p0.023Regression, Logistic

Odds Ratio (OR)2.1495% CI1.44 – 3.17p<0.001Regression, Logistic

Odds Ratio (OR)3.0395% CI1.97 – 4.66p<0.001Regression, Logistic

Secondary/registry result

Change From Baseline in Fasting Serum Glucose (FSG)

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Value (least_squares_mean), milligram per Deciliter (mg/dL)	95% CI
5 mg Tirzepatide	-56.0	—
10 mg Tirzepatide	-61.6	—
15 mg Tirzepatide	-63.4	—
1 mg Semaglutide	-48.6	—

LS Mean Difference-7.395% CI-11.7 – -3.0p0.001Mixed Models Analysis

LS Mean Difference-13.095% CI-17.4 – -8.6p<0.001Mixed Models Analysis

LS Mean Difference-14.795% CI-19.1 – -10.3p<0.001Mixed Models Analysis

Secondary/registry result

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

Time frame:Baseline, Week 40

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
5 mg Tirzepatide	-65.4	—
10 mg Tirzepatide	-70.6	—
15 mg Tirzepatide	-74.3	—
1 mg Semaglutide	-61.4	—

Secondary/registry result

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

Time frame:Week 40

HbA1c <5.7% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of Participants	95% CI
5 mg Tirzepatide	29.28	—
10 mg Tirzepatide	44.66	—
15 mg Tirzepatide	50.86	—
1 mg Semaglutide	19.74	—

Odds Ratio (OR)1.8695% CI1.35 – 2.57p<0.001Regression, Logistic

Odds Ratio (OR)3.9495% CI2.88 – 5.39p<0.001Regression, Logistic

Odds Ratio (OR)5.1095% CI3.73 – 6.97p<0.001Regression, Logistic

Secondary/protocol endpoint

Change From Baseline in HbA1c (5 mg)

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

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

Time frame:Week 40

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Baseline in Fasting Serum Glucose (FSG)

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

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

Time frame:Baseline, Week 40

change from baseline, improvement

Secondary/protocol endpoint

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

Time frame:Week 40

HbA1c <5.7% achievement

threshold achievement, improvement

LOINC 4548-4

Patient-reported / QoL

2 endpoints

Secondary/registry result

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

Time frame:Baseline, Week 40

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a Scale	95% CI
5 mg TirzepatideHyperglycemia	-1.3	—
Hypoglycemia	-0.7	—
Total Score	15.7	—
10 mg TirzepatideHyperglycemia	-1.4	—
Hypoglycemia	-0.7	—
Total Score	15.6	—
15 mg TirzepatideHyperglycemia	-1.5	—
Hypoglycemia	-0.8	—
Total Score	16.1	—
1 mg SemaglutideHyperglycemia	-1.1	—
Hypoglycemia	-0.7	—
Total Score	15.8	—

LS Mean Difference-0.2495% CI-0.50 – 0.03p0.084ANCOVA

Hyperglycemia

LS Mean Difference-0.2795% CI-0.54 – 0.00p0.050ANCOVA

Hyperglycemia

LS Mean Difference-0.3995% CI-0.66 – -0.12p0.005ANCOVA

Hyperglycemia

LS Mean Difference-0.0695% CI-0.33 – 0.22p0.688ANCOVA

Hypoglycemia

LS Mean Difference-0.0295% CI-0.29 – 0.26p0.909ANCOVA

Hypoglycemia

LS Mean Difference-0.1395% CI-0.40 – 0.15p0.358ANCOVA

Hypoglycemia

LS Mean Difference-0.1095% CI-0.62 – 0.41p0.701ANCOVA

Total Score

LS Mean Difference-0.2595% CI-0.78 – 0.27p0.341ANCOVA

Total Score

LS Mean Difference0.2695% CI-0.26 – 0.79p0.321ANCOVA

Total Score

Secondary/protocol endpoint

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

Time frame:Baseline, Week 40

change from baseline, improvement

Safety / tolerability / PK

2 endpoints

Secondary/registry result

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)

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Posted result

Group	Value (mean), Episodes/participant/365.25 days	95% CI
5 mg Tirzepatide	0.0102	—
10 mg Tirzepatide	0.0046	—
15 mg Tirzepatide	0.0202	—
1 mg Semaglutide	0.0046	—

Secondary/protocol endpoint

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)

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Publications (11)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Tirzepatide for Older Adults with Type 2 Diabetes and Without Obesity: A Post Hoc Analysis of the SURPASS Clinical Trials.
Diabetes therapy : research, treatment and education of diabetes and related disorders2025 Apr (month)PMID40016573doi:10.1007/s13300-025-01711-0via pubmed nct search
Post Hoc Analysis of SURPASS-1 to -5: Efficacy and Safety of Tirzepatide in Adults with Type 2 Diabetes are Independent of Baseline Characteristics.
Diabetes therapy : research, treatment and education of diabetes and related disorders2025 Jan (month)PMID39531161doi:10.1007/s13300-024-01660-0via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide 5, 10 and 15 mg versus injectable semaglutide 0.5 mg for the treatment of type 2 diabetes: An adjusted indirect treatment comparison.
Diabetes research and clinical practice2024 Jun (month)PMID38777128doi:10.1016/j.diabres.2024.111717via clinicaltrials gov reference derived + pubmed nct search
Patient-Reported Outcomes in People with Type 2 Diabetes Receiving Tirzepatide in the SURPASS Clinical Trial Programme.
Diabetes therapy : research, treatment and education of diabetes and related disorders2023 Nov (month)PMID37526908doi:10.1007/s13300-023-01451-zvia clinicaltrials gov reference derived + pubmed nct search
Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.
Diabetes therapy : research, treatment and education of diabetes and related disorders2023 Nov (month)PMID37668888doi:10.1007/s13300-023-01457-7via clinicaltrials gov reference derived + pubmed nct search
Semaglutide versus tirzepatide for people with type 2 diabetes: cost of glycemic control in Austria, the Netherlands, Lithuania, and the United Arab Emirates.
Current medical research and opinion2023 Aug (month)PMID37415503doi:10.1080/03007995.2023.2231275via clinicaltrials gov reference derived + pubmed nct search
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.
Diabetes therapy : research, treatment and education of diabetes and related disorders2023 May (month)PMID37000390doi:10.1007/s13300-023-01398-1via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide-Friend or Foe in Diabetic Cancer Patients?
Biomolecules2022 Oct 28PMID36358930doi:10.3390/biom12111580via pubmed nct search
Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2022 Sep (month)PMID35489606doi:10.1016/j.cmi.2022.04.009via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.
Nature medicine2022 Mar (month)PMID35210595doi:10.1038/s41591-022-01707-4via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.
The New England journal of medicine2021 Aug 5PMID34170647doi:10.1056/NEJMoa2107519via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.