SURPASS-3

CompletedPhase 3Results posted

A Study of Tirzepatide (LY3298176) Versus Insulin Degludec in Participants With Type 2 Diabetes

A Randomized, Phase 3, Open-Label Trial Comparing the Effect of LY3298176 Versus Titrated Insulin Degludec on Glycemic Control in Patients With Type 2 Diabetes

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

122

Recruiting sites

Actual enrollment

1,444

Study population

Type 2 diabetes

Eligibility highlights

•BMI ≥25•HbA1c 7-10.5%

Primary endpoint

•HbA1c, change

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT03882970

Org study ID16997

Secondary ID2018-003422-84

Secondary IDI8F-MC-GPGHEli Lilly and Company

Timeline

Milestones

Study first posted2019-03-20actual

Study start2019-04-01actual

Primary completion2020-12-11actual

Study completion2021-01-04actual

Last update posted2022-01-19actual

Results first posted2022-01-19actual

Assets

Investigational agents

Tirzepatide

Who this study enrolls

Type 2 diabetes

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participants must:

-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 or metformin plus an SGLT-2 inhibitor for at least 3 months before screening

-Be of stable weight (± 5%) for at least 3 months before screening

-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 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 their ALT level is ≤3.0 the ULN for the reference range

-Have an estimated glomerular filtration rate <45 mL/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, or metformin plus an SGLT-2 inhibitor during the last 3 months

-Have been taking weight loss drugs, including over-the-counter medications during the last 3 months

Endpoints (18)

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 52

Body weight, absolute change (kg)

change from baseline, improvement

Posted result

Group	Least-squares mean · Kilograms (kg)	95% CI
5 mg Tirzepatide	-7.5	-
10 mg Tirzepatide	-10.7	-
15 mg Tirzepatide	-12.9	-
Insulin Degludec	2.3	-

Ls mean difference-9.895% CI-10.8 - -8.8p<0.001Mixed Models Analysis

Ls mean difference-13.095% CI-14.0 - -11.9p<0.001Mixed Models Analysis

Ls mean difference-15.295% CI-16.2 - -14.2p<0.001Mixed Models Analysis

Secondary/registry result

Percentage of Participants Who Achieved Weight Loss ≥5%

Time frame:Week 52

≥5% weight-loss responders

threshold achievement, improvement

Posted result

Group	Number · percentage of participants	95% CI
5 mg Tirzepatide	66.01	-
10 mg Tirzepatide	83.71	-
15 mg Tirzepatide	87.82	-
Insulin Degludec	6.27	-

Odds ratio (or)29.7895% CI18.35 - 48.35p<0.001Regression, Logistic

Odds ratio (or)79.8895% CI47.56 - 134.17p<0.001Regression, Logistic

Odds ratio (or)110.7795% CI64.73 - 189.55p<0.001Regression, Logistic

Secondary/protocol endpoint

Change From Baseline in Body Weight

Time frame:Baseline, Week 52

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved Weight Loss ≥5%

Time frame:Week 52

≥5% weight-loss responders

threshold achievement, improvement

Glycemic / diabetes

10 endpoints

Primary/registry result

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

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Least-squares mean · % HbA1c	95% CI
10 mg Tirzepatide	-2.20	-
15 mg Tirzepatide	-2.37	-
Insulin Degludec	-1.34	-

Ls mean difference-0.8695% CI-1.00 - -0.72p<0.001Mixed Models Analysis

Ls mean difference-1.0495% CI-1.17 - -0.90p<0.001Mixed Models Analysis

Primary/protocol endpoint

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

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Change From Baseline in HbA1c (5 mg)

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Least-squares mean · % HbA1c	95% CI
5 mg Tirzepatide	-1.93	-
Insulin Degludec	-1.34	-

Ls mean difference-0.5995% CI-0.73 - -0.45p<0.001Mixed Models Analysis

Secondary/registry result

Change From Baseline in Fasting Serum Glucose

Time frame:Baseline, Week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Posted result

Group	Least-squares mean · milligram per Deciliter (mg/dL)	95% CI
5 mg Tirzepatide	-48.2	-
10 mg Tirzepatide	-54.8	-
15 mg Tirzepatide	-59.2	-
Insulin Degludec	-55.7	-

Ls mean difference7.595% CI2.4 - 12.5p0.004Mixed Models Analysis

Ls mean difference0.895% CI-4.3 - 5.9p0.751Mixed Models Analysis

Ls mean difference-3.695% CI-8.7 - 1.5p0.168Mixed Models Analysis

Secondary/registry result

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

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Number · percentage of participants	95% CI
5 mg Tirzepatide	82.44	-
10 mg Tirzepatide	89.71	-
15 mg Tirzepatide	92.63	-
Insulin Degludec	61.25	-

Odds ratio (or)3.4595% CI2.38 - 5.01p<0.001Regression, Logistic

Odds ratio (or)7.0295% CI4.55 - 10.84p<0.001Regression, Logistic

Odds ratio (or)10.7995% CI6.65 - 17.48p<0.001Regression, Logistic

Secondary/registry result

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

Time frame:Baseline, Week 52

change from baseline, improvement

Posted result

Group	Least-squares mean · mg/dL	95% CI
5 mg Tirzepatide	-52.6	-
10 mg Tirzepatide	-59.7	-
15 mg Tirzepatide	-60.6	-
Insulin Degludec	-48.0	-

Secondary/protocol endpoint

Change From Baseline in HbA1c (5 mg)

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Change From Baseline in Fasting Serum Glucose

Time frame:Baseline, Week 52

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

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

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Secondary/protocol endpoint

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

Time frame:Baseline, Week 52

change from baseline, improvement

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 Treatment Satisfaction Score

Time frame:Week 52

change from baseline, improvement

Posted result

Group	Least-squares mean · units on a scale	95% CI
5 mg TirzepatideHyperglycemia	-1.4	-
Hypoglycemia	-1.1	-
Treatment Satisfaction Score	15.6	-
10 mg TirzepatideHyperglycemia	-1.4	-
Hypoglycemia	-0.9	-
Treatment Satisfaction Score	15.5	-
15 mg TirzepatideHyperglycemia	-1.6	-
Hypoglycemia	-1.0	-
Treatment Satisfaction Score	15.6	-
Insulin DegludecHyperglycemia	-1.1	-
Hypoglycemia	-0.7	-
Treatment Satisfaction Score	12.6	-

Ls mean difference-0.2695% CI-0.57 - 0.05p0.096ANCOVA

Hyperglycemia

Ls mean difference-0.2595% CI-0.57 - 0.06p0.113ANCOVA

Hyperglycemia

Ls mean difference-0.4795% CI-0.78 - -0.16p0.003ANCOVA

Hyperglycemia

Ls mean difference-0.4195% CI-0.74 - -0.08p0.014ANCOVA

Hypoglycemia

Ls mean difference-0.1895% CI-0.51 - 0.15p0.280ANCOVA

Hypoglycemia

Ls mean difference-0.2695% CI-0.59 - 0.07p0.129ANCOVA

Hypoglycemia

Ls mean difference3.0195% CI2.26 - 3.75p<0.001ANCOVA

Treatment Satisfaction Score

Ls mean difference2.9095% CI2.15 - 3.65p<0.001ANCOVA

Treatment Satisfaction Score

Ls mean difference2.9995% CI2.24 - 3.74p<0.001ANCOVA

Treatment Satisfaction Score

Secondary/protocol endpoint

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

Time frame:Week 52

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 56)

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Posted result

Group	Mean · Episodes/participant/365.25 days	95% CI
5 mg Tirzepatide	0.0137	-
10 mg Tirzepatide	0.0108	-
15 mg Tirzepatide	0.0275	-
Insulin Degludec	0.1020	-

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 56)

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 and muscle composition changes in people with type 2 diabetes (SURPASS-3 MRI): a post-hoc analysis of a randomised, open-label, parallel-group, phase 3 trial.
The lancet. Diabetes & endocrinology2025 Jun (month)PMID40318682doi:10.1016/S2213-8587(25)00027-0via clinicaltrials gov reference derived + pubmed nct search
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
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
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
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
Efficacy of once-weekly tirzepatide versus once-daily insulin degludec on glycaemic control measured by continuous glucose monitoring in adults with type 2 diabetes (SURPASS-3 CGM): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial.
The lancet. Diabetes & endocrinology2022 Jun (month)PMID35468321doi:10.1016/S2213-8587(22)00077-8via clinicaltrials gov reference derived + pubmed nct search
Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial.
The lancet. Diabetes & endocrinology2022 Jun (month)PMID35468325doi:10.1016/S2213-8587(22)00070-5via 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
Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.
Lancet (London, England)2021 Aug 14PMID34370970doi:10.1016/S0140-6736(21)01443-4via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 6, 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 6, 2026 snapshot.