SURPASS-5

CompletedPhase 3Results posted

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

Randomized, Phase 3, Double-blind Trial Comparing the Effect of the Addition of Tirzepatide Versus Placebo in Patients With Type 2 Diabetes Inadequately Controlled on Insulin Glargine With or Without Metformin

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

—

Enrollment

475

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥23•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 IDNCT04039503

Org study ID16998

Secondary ID2019-000860-99

Secondary IDI8F-MC-GPGIEli Lilly and Company

Timeline

Milestones

Study first posted2019-07-31actual

Study start2019-08-30actual

Primary completion2020-12-22actual

Study completion2021-01-13actual

Last update posted2022-01-12actual

Results first posted2022-01-12actual

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) 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.

Endpoints (22)

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	-6.2	—
10 mg Tirzepatide	-8.2	—
15 mg Tirzepatide	-10.9	—
Placebo	1.7	—

LS Mean Difference-7.895% CI-9.4 – -6.3p<0.001Mixed Models Analysis

LS Mean Difference-9.995% CI-11.5 – -8.3p<0.001Mixed Models Analysis

LS Mean Difference-12.695% CI-14.2 – -11.0p<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	53.91	—
10 mg Tirzepatide	64.60	—
15 mg Tirzepatide	84.62	—
Placebo	5.93	—

Odds Ratio (OR)17.1595% CI7.55 – 38.93p<0.001Regression, Logistic

Odds Ratio (OR)27.2495% CI11.87 – 62.55p<0.001Regression, Logistic

Odds Ratio (OR)79.6195% CI32.76 – 193.44p<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

14 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	-2.59	—
15 mg Tirzepatide	-2.59	—
Placebo	-0.93	—

LS Mean Difference-1.6695% CI-1.88 – -1.43p<0.001Mixed Models Analysis

LS Mean Difference-1.6595% CI-1.88 – -1.43p<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	-2.23	—
Placebo	-0.93	—

LS Mean Difference-1.3095% CI-1.52 – -1.07p<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	93.04	—
10 mg Tirzepatide	97.35	—
15 mg Tirzepatide	94.02	—
Placebo	33.90	—

Odds Ratio (OR)37.7795% CI15.23 – 93.70p<0.001Regression, Logistic

Odds Ratio (OR)100.0795% CI30.02 – 333.62p<0.001Regression, Logistic

Odds Ratio (OR)43.3195% CI16.92 – 110.83p<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	-61.4	—
10 mg Tirzepatide	-67.9	—
15 mg Tirzepatide	-67.7	—
Placebo	-38.9	—

LS Mean Difference-22.595% CI-29.5 – -15.4p<0.001Mixed Models Analysis

LS Mean Difference-29.095% CI-36.0 – -22.0p<0.001Mixed Models Analysis

LS Mean Difference-28.895% CI-35.9 – -21.6p<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	-67.1	—
10 mg Tirzepatide	-71.7	—
15 mg Tirzepatide	-73.7	—
Placebo	-39.4	—

Secondary/registry result

Percentage Change From Baseline in Daily Mean Insulin Glargine Dose

Time frame:Baseline, Week 40

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), International Units (IU)	95% CI
5 mg Tirzepatide	13.0	—
10 mg Tirzepatide	8.1	—
15 mg Tirzepatide	-11.4	—
Placebo	75.0	—

Estimate Difference-35.495% CI-46.0 – -22.8

Estimate Difference-38.295% CI-48.3 – -26.1

Estimate Difference-49.395% CI-57.7 – -39.4

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	26.09	—
10 mg Tirzepatide	47.79	—
15 mg Tirzepatide	62.39	—
Placebo	2.54	—

Odds Ratio (OR)12.2295% CI3.93 – 38.00p<0.001Regression, Logistic

Odds Ratio (OR)32.3695% CI10.52 – 99.49p<0.001Regression, Logistic

Odds Ratio (OR)56.2695% CI18.27 – 173.26p<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

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 Change From Baseline in Daily Mean Insulin Glargine Dose

Time frame:Baseline, Week 40

percent 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

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 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	0.49	—
10 mg Tirzepatide	0.66	—
15 mg Tirzepatide	0.38	—
Placebo	0.51	—

Secondary/registry result

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

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

Plasma concentration (steady state)

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanogramhour per milliliter (ngh/mL)	95% CI
5 mg Tirzepatide	79700	—
10 mg Tirzepatide	164000	—
15 mg Tirzepatide	246000	—

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

Secondary/protocol endpoint

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

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

AUC₀–∞

concentration, descriptive

Publications (8)

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 as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.
Diabetes therapy : research, treatment and education of diabetes and related disorders2026 May (month)PMID41961454doi:10.1007/s13300-026-01859-3via 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
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
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.
JAMA2022 Feb 8PMID35133415doi:10.1001/jama.2022.0078via 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.