SURPASS-1

CompletedPhase 3Results posted

A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

A Randomized, Double-blind, Placebo-Controlled Trial Comparing the Efficacy and Safety of Three Tirzepatide Doses Versus Placebo in Patients With Type 2 Diabetes, Inadequately Controlled With Diet and Exercise Alone

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

—

Enrollment

478

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥23•HbA1c 7-9.5%

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 IDNCT03954834

Org study ID17000

Secondary IDI8F-MC-GPGKEli Lilly and Company

Timeline

Milestones

Study first posted2019-05-17actual

Study start2019-06-03actual

Primary completion2020-10-05actual

Study completion2020-10-28actual

Last update posted2021-10-20actual

Results first posted2021-10-20actual

Assets

Investigational agents

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).

•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.

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

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	-7.0	—
10 mg Tirzepatide	-7.8	—
15 mg Tirzepatide	-9.5	—
Placebo	-0.7	—

LS Mean Difference-6.395% CI-7.8 – -4.7p<0.001Mixed Models Analysis

LS Mean Difference-7.195% CI-8.6 – -5.5p<0.001Mixed Models Analysis

LS Mean Difference-8.895% CI-10.3 – -7.2p<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	66.94	—
10 mg Tirzepatide	77.97	—
15 mg Tirzepatide	76.72	—
Placebo	14.29	—

Odds Ratio (OR)12.4095% CI6.43 – 23.94p<0.001Regression, Logistic

Odds Ratio (OR)21.1395% CI10.59 – 42.18p<0.001Regression, Logistic

Odds Ratio (OR)20.1095% CI10.09 – 40.04p<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

10 endpoints

Primary/registry result

Change From Baseline in Hemoglobin A1c (HbA1c)

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	-1.87	—
10 mg Tirzepatide	-1.89	—
15 mg Tirzepatide	-2.07	—
Placebo	0.04	—

LS Mean Difference-1.9195% CI-2.18 – -1.63p<0.001Mixed Models Analysis

LS Mean Difference-1.9395% CI-2.21 – -1.65p<0.001Mixed Models Analysis

LS Mean Difference-2.1195% CI-2.39 – -1.83p<0.001Mixed Models Analysis

Primary/protocol endpoint

Change From Baseline in Hemoglobin A1c (HbA1c)

Time frame:Baseline, Week 40

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/registry result

Percentage of Participants With 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	86.78	—
10 mg Tirzepatide	91.53	—
15 mg Tirzepatide	87.93	—
Placebo	19.64	—

Odds Ratio (OR)49.0095% CI21.12 – 113.67p<0.001Regression, Logistic

Odds Ratio (OR)80.3995% CI31.80 – 203.19p<0.001Regression, Logistic

Odds Ratio (OR)52.9595% CI22.30 – 125.73p<0.001Regression, Logistic

Secondary/registry result

Change From Baseline in Fasting Serum Glucose

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	-43.6	—
10 mg Tirzepatide	-45.9	—
15 mg Tirzepatide	-49.3	—
Placebo	12.9	—

LS Mean Difference-1.595% CI-11.9 – 8.9p0.776Mixed Models Analysis

LS Mean Difference-2.695% CI-13.0 – 7.8p0.622Mixed Models Analysis

LS Mean Difference-0.695% CI-11.1 – 9.8p0.908Mixed Models Analysis

Secondary/registry result

Percentage of Participants With 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	33.88	—
10 mg Tirzepatide	30.51	—
15 mg Tirzepatide	51.72	—
Placebo	0.89	—

Odds Ratio (OR)40.2895% CI7.74 – 209.71p<0.001Regression, Logistic

Odds Ratio (OR)34.1295% CI6.53 – 178.19p<0.001Regression, Logistic

Odds Ratio (OR)85.1395% CI16.36 – 443.13p<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 40

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), mg/dL	95% CI
5 mg TirzepatideMorning Premeal - Fasting	-46.9	—
Morning 2-hour Postmeal	-69.5	—
Midday Premeal	-43.5	—
Midday 2-hour Postmeal	-64.2	—
Evening Premeal	-44.8	—
Evening 2-hour Postmeal	-61.9	—
Bedtime	-57.0	—
10 mg TirzepatideMorning Premeal - Fasting	-47.9	—
Morning 2-hour Postmeal	-61.4	—
Midday Premeal	-42.5	—
Midday 2-hour Postmeal	-60.0	—
Evening Premeal	-45.1	—
Evening 2-hour Postmeal	-62.8	—
Bedtime	-59.8	—
15 mg TirzepatideMorning Premeal - Fasting	-45.7	—
Morning 2-hour Postmeal	-68.9	—
Midday Premeal	-42.7	—
Midday 2-hour Postmeal	-63.4	—
Evening Premeal	-42.3	—
Evening 2-hour Postmeal	-63.5	—
Bedtime	-60.8	—
PlaceboMorning Premeal - Fasting	-9.2	—
Morning 2-hour Postmeal	-11.6	—
Midday Premeal	-2.6	—
Midday 2-hour Postmeal	-12.7	—
Evening Premeal	-5.8	—
Evening 2-hour Postmeal	-10.3	—
Bedtime	-9.1	—

LS Mean Difference-37.795% CI-44.1 – -31.2p<0.001Mixed Models Analysis

Morning Premeal - Fasting

LS Mean Difference-38.695% CI-45.1 – -32.2p<0.001Mixed Models Analysis

Morning Premeal - Fasting

LS Mean Difference-36.595% CI-43.1 – -29.8p<0.001Mixed Models Analysis

Morning Premeal - Fasting

LS Mean Difference-57.995% CI-68.4 – -47.4p<0.001Mixed Models Analysis

Morning 2-hour Postmeal

LS Mean Difference-49.795% CI-60.3 – -39.2p<0.001Mixed Models Analysis

Morning 2-hour Postmeal

LS Mean Difference-57.395% CI-68.1 – -46.4p<0.001Mixed Models Analysis

Morning 2-hour Postmeal

LS Mean Difference-40.995% CI-49.6 – -32.2p<0.001Mixed Models Analysis

Midday Premeal

LS Mean Difference-39.995% CI-48.6 – -31.2p<0.001Mixed Models Analysis

Midday Premeal

LS Mean Difference-40.095% CI-49.0 – -31.1p<0.001Mixed Models Analysis

Midday Premeal

LS Mean Difference-51.495% CI-62.5 – -40.4p<0.001Mixed Models Analysis

Midday 2-hour Postmeal

LS Mean Difference-47.395% CI-58.4 – -36.2p<0.001Mixed Models Analysis

Midday 2-hour Postmeal

LS Mean Difference-50.795% CI-62.1 – -39.3p<0.001Mixed Models Analysis

Midday 2-hour Postmeal

LS Mean Difference-39.095% CI-47.6 – -30.4p<0.001Mixed Models Analysis

Evening Premeal

LS Mean Difference-39.295% CI-47.9 – -30.6p<0.001Mixed Models Analysis

Evening Premeal

LS Mean Difference-36.495% CI-45.3 – -27.5p<0.001Mixed Models Analysis

Evening Premeal

LS Mean Difference-51.795% CI-63.2 – -40.1p<0.001Mixed Models Analysis

Evening 2-hour Postmeal

LS Mean Difference-52.595% CI-64.1 – -40.9p<0.001Mixed Models Analysis

Evening 2-hour Postmeal

LS Mean Difference-53.295% CI-65.1 – -41.3p<0.001Mixed Models Analysis

Evening 2-hour Postmeal

LS Mean Difference-48.095% CI-58.6 – -37.4p<0.001Mixed Models Analysis

Bedtime

LS Mean Difference-50.795% CI-61.3 – -40.1p<0.001Mixed Models Analysis

Bedtime

LS Mean Difference-51.795% CI-62.6 – -40.9p<0.001Mixed Models Analysis

Secondary/protocol endpoint

Percentage of Participants With 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

Time frame:Baseline, Week 40

Fasting glucose, change

change from baseline, improvement

LOINC 1558-6

Secondary/protocol endpoint

Percentage of Participants With HbA1c Target Value of <5.7%

Time frame:Week 40

HbA1c <5.7% 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 40

change from baseline, improvement

Safety / tolerability / PK

4 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 end of 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	0.02	—
10 mg Tirzepatide	0.02	—
15 mg Tirzepatide	0.02	—
Placebo	0.04	—

Secondary/registry result

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

Time frame:Week 7, 15 and 23

AUC₀–∞

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanogramshours per milliliter (hng/mL)	95% CI
5 mg Tirzepatide	86900	—
10 mg Tirzepatide	171000	—
15 mg Tirzepatide	252000	—

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 end of safety follow-up (up to week 44)

Documented hypoglycemia

event count, event

componentsDocumented hypoglycemia, Severe hypoglycemia

Secondary/protocol endpoint

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

Time frame:Week 7, 15 and 23

AUC₀–∞

concentration, descriptive

Publications (7)

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
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
Tirzepatide-Friend or Foe in Diabetic Cancer Patients?
Biomolecules2022 Oct 28PMID36358930doi:10.3390/biom12111580via 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
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.
Lancet (London, England)2021 Jul 10PMID34186022doi:10.1016/S0140-6736(21)01324-6via 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.