SURPASS-6

CompletedPhase 3Results posted

A Study of Tirzepatide (LY3298176) Versus Insulin Lispro (U100) in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin

A Randomized, Phase 3, Open-label Trial Comparing the Effect of the Addition of Tirzepatide Once Weekly Versus Insulin Lispro (U100) Three Times Daily in Participants With Type 2 Diabetes Inadequately Controlled on Insulin Glargine (U100) With or Without Metformin (SURPASS-6)

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

135

Recruiting sites

—

Enrollment

1,428

actual

Study population

Type 2 diabetes

Key I/E criteria

•BMI ≥23•HbA1c 7.5-11%

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 IDNCT04537923

Org study ID17204

Secondary ID2020-000284-23

Secondary IDI8F-MC-GPHDEli Lilly and Company

Timeline

Milestones

Study first posted2020-09-03actual

Study start2020-10-19actual

Primary completion2022-10-11actual

Study completion2022-11-01actual

Last update posted2023-11-02actual

Results first posted2023-11-02actual

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)

•Have HbA1c between ≥7.5% and ≤11%

•Have been treated for at least 90 days prior to day of screening with once or twice daily basal insulin with or without stable dose of metformin ≥1500 mg/day and up to maximum approved dose per country specific approved label, sulfonylureas or dipeptidyl peptidase 4 inhibitors

•Be of stable weight (± 5%) for at least 90 days

•Have a BMI ≥23 kilograms per meter squared (kg/m²) and ≤45 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 macular edema or nonproliferative diabetic retinopathy requiring immediate or urgent treatment

•Have disorders associated with slowed emptying of the stomach, have had any stomach surgeries for the purpose of weight loss, or are chronically taking drugs that directly affect gastrointestinal motility

•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

•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)]

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

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	Value (least_squares_mean), Kilograms (kg)	95% CI
5 mg Tirzepatide	-6.9	—
10 mg Tirzepatide	-9.9	—
15 mg Tirzepatide	-12.0	—
Insulin Lispro	3.8	—

LS Mean Difference-10.795% CI-11.5 – -9.9p<0.001Mixed Models Analysis

LS Mean Difference-13.795% CI-14.5 – -12.9p<0.001Mixed Models Analysis

LS Mean Difference-15.995% CI-16.7 – -15.0p<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	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	64.19	—
10 mg Tirzepatide	79.21	—
15 mg Tirzepatide	83.15	—
Insulin Lispro	6.34	—

Odds Ratio (OR)28.2595% CI18.36 – 43.46p<0.001Regression, Logistic

Odds Ratio (OR)58.9095% CI36.76 – 94.39p<0.001Regression, Logistic

Odds Ratio (OR)77.7695% CI47.49 – 127.33p<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

12 endpoints

Primary/registry result

Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 10 mg and 15 mg)

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), Percentage of HbA1c	95% CI
Pooled 5 mg/10 mg/15 mg Tirzepatide	-2.26	—
Insulin Lispro	-1.16	—

LS Mean Difference-1.1095% CI-1.24 – -0.97p<0.001Mixed Models Analysis

Primary/protocol endpoint

Change From Baseline in Hemoglobin A1c (HbA1c) (Pooled Doses of Tirzepatide 5 mg, 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

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Posted result

Group	Value (least_squares_mean), Percentage of HbA1c	95% CI
5 mg Tirzepatide	-2.05	—
10 mg Tirzepatide	-2.27	—
15 mg Tirzepatide	-2.46	—
Insulin Lispro	-1.16	—

LS Mean Difference-0.8995% CI-1.08 – -0.70p<0.001Mixed Models Analysis

LS Mean Difference-1.1195% CI-1.30 – -0.92p<0.001Mixed Models Analysis

LS Mean Difference-1.3095% CI-1.49 – -1.11p<0.001Mixed Models Analysis

Secondary/registry result

Percentage of Participants With HbA1c Target Values <7.0%

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	61.04	—
10 mg Tirzepatide	75.64	—
15 mg Tirzepatide	79.86	—
Insulin Lispro	36.69	—

Odds Ratio (OR)3.1395% CI2.25 – 4.36p<0.0001Regression, Logistic

Odds Ratio (OR)6.1695% CI4.27 – 8.88p<0.0001Regression, Logistic

Odds Ratio (OR)7.9495% CI5.37 – 11.75p<0.0001Regression, Logistic

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	Value (least_squares_mean), milligram per Deciliter (mg/dL)	95% CI
5 mg Tirzepatide	-33.2	—
10 mg Tirzepatide	-43.0	—
15 mg Tirzepatide	-41.6	—
Insulin Lispro	-10.0	—

LS Mean Difference-23.295% CI-30.8 – -15.7p<0.001Mixed Models Analysis

LS Mean Difference-33.095% CI-40.6 – -25.4p<0.001Mixed Models Analysis

LS Mean Difference-31.695% CI-39.3 – -23.8p<0.001Mixed Models Analysis

Secondary/registry result

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	Value (least_squares_mean), mg/dL/day	95% CI
5 mg Tirzepatide	-56.7	—
10 mg Tirzepatide	-61.5	—
15 mg Tirzepatide	67.6	—
Insulin Lispro	-55.8	—

LS Mean Difference-0.995% CI-5.0 – 3.3p0.682Mixed Models Analysis

LS Mean Difference-5.695% CI-9.9 – -1.4p0.010Mixed Models Analysis

LS Mean Difference-11.895% CI-16.0 – -7.5p<0.001Mixed Models Analysis

Secondary/registry result

Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Posted result

Group	Value (number), Percentage of participants	95% CI
5 mg Tirzepatide	52.70	—
10 mg Tirzepatide	70.05	—
15 mg Tirzepatide	75.12	—
Insulin Lispro	13.41	—

Odds Ratio (OR)8.1995% CI5.66 – 11.83p<0.001Regression, Logistic

Odds Ratio (OR)16.9095% CI11.44 – 24.96p<0.001Regression, Logistic

Odds Ratio (OR)21.8595% CI14.49 – 32.93p<0.001Regression, Logistic

Secondary/protocol endpoint

Change From Baseline in HbA1c

Time frame:Baseline, Week 52

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Percentage of Participants With HbA1c Target Values <7.0%

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, 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

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

Time frame:Baseline, Week 52

Postprandial glucose

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Who Achieved HbA1c Target Value of <7.0% Without Hypoglycemia

Time frame:Week 52

HbA1c <7.0% achievement

threshold achievement, improvement

LOINC 4548-4

Patient-reported / QoL

4 endpoints

Secondary/registry result

Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

Time frame:Baseline, Week 52

SF-36 physical

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	95% CI
5 mg Tirzepatide	1.0	—
10 mg Tirzepatide	1.7	—
15 mg Tirzepatide	1.7	—
Insulin Lispro	-0.6	—

LS Mean Difference1.595% CI0.5 – 2.6p0.005ANCOVA

LS Mean Difference2.395% CI1.2 – 3.3p<0.001ANCOVA

LS Mean Difference2.295% CI1.2 – 3.3p<0.001ANCOVA

Secondary/registry result

Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score

Time frame:Baseline, Week 52

SF-36 mental

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), score on a scale	95% CI
5 mg Tirzepatide	0.3	—
10 mg Tirzepatide	1.5	—
15 mg Tirzepatide	0.7	—
Insulin Lispro	-1.3	—

LS Mean Difference1.695% CI0.3 – 2.9p0.020ANCOVA

LS Mean Difference2.895% CI1.5 – 4.2p<0.001ANCOVA

LS Mean Difference2.195% CI0.7 – 3.5p0.004ANCOVA

Secondary/protocol endpoint

Change From Baseline in 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) Score

Time frame:Baseline, Week 52

SF-36 physical

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in 36-Item SF-36 Mental Component Summary (MCS) Score

Time frame:Baseline, Week 52

SF-36 mental

change from baseline, improvement

Publications (3)

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 Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).
Diabetes therapy : research, treatment and education of diabetes and related disorders2024 Sep (month)PMID39008236doi:10.1007/s13300-024-01620-8via pubmed nct search
Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial.
JAMA2023 Nov 7PMID37786396doi:10.1001/jama.2023.20294via 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.