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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

Short name SURPASS-6

NCTNCT04537923 (opens ClinicalTrials.gov in a new tab)Other id17204Other idI8F-MC-GPHDOther id2020-000284-23
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
1,428 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Open label (no masking)
Countries
16 countries

United States, Argentina, Belgium, Brazil, Czechia, Germany, Greece, Hungary, Italy, Mexico, Puerto Rico, Romania, Russia, Slovakia, Spain, Turkey (Türkiye)

Start
19 Oct 2020
Primary completion
11 Oct 2022
Completion
1 Nov 2022
First posted
3 Sept 2020
Last update posted
2 Nov 2023
Conditions
Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2020202120222023
  1. Ph 3

    SURPASS-6

    NCT04537923

    19 Oct 2020 to 1 Nov 2022

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

The purpose of this study is to compare the safety and efficacy of the study drug tirzepatide to insulin lispro (U100) three times a day in participants with type 2 diabetes that are already on insulin glargine (U100), with or without metformin.

Interventions

  • TirzepatideDrug
  • Insulin Lispro (U100)Drug

Arms4

  • Experimental

    5 mg Tirzepatide

    5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

  • Experimental

    10 mg Tirzepatide

    10 mg tirzepatide administered SC once a week.

  • Experimental

    15 mg Tirzepatide

    15 mg tirzepatide administered SC once a week.

  • Active comparator

    Insulin Lispro

    Insulin lispro 100 units per milliliter (U100) administered SC three times a day.

Primary outcomes1

Outcomes the sponsor listed as primary.

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

    Time frame · Baseline, Week 52

    Registry description

    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary outcomes(9)

  1. Change From Baseline in HbA1c

    Time frame · Baseline, Week 52

    Registry description

    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by MMRM model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

  2. Percentage of Participants With HbA1c Target Values <7.0%

    Time frame · Week 52

    Registry description

    HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

  3. Change From Baseline in Body Weight

    Time frame · Baseline, Week 52

    Registry description

    LS mean was determined by MMRM model with Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

  4. Change From Baseline in Fasting Serum Glucose

    Time frame · Baseline, Week 52

    Registry description

    LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

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

    Time frame · Baseline, Week 52

    Registry description

    The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post meal, Midday Premeal, Midday 2-hour Post meal, Evening Premeal, Evening 2-hour Post meal and Bedtime. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS mean was determined by MMRM model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares).

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

    Time frame · Week 52

    Registry description

    Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

  7. Percentage of Participants Who Achieved Weight Loss ≥5%

    Time frame · Week 52

    Registry description

    Percentage of Participants who Achieved Weight Loss ≥5% is reported here.

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

    Time frame · Baseline, Week 52

    Registry description

    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. PCS consisted of physical functioning, bodily pain, role-physical, and general health scales. PCS score is reported here. PCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by analysis of covariance (ANCOVA) model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

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

    Time frame · Baseline, Week 52

    Registry description

    The SF-36 is a health-related survey that assesses participant's quality of life and consists of 36 questions covering 8 health domains: physical functioning, bodily pain, role limitations due to physical problems and emotional problems, general health, mental health, social functioning, vitality, and two overall summary scores: physical component summary (PCS) and mental component summary (MCS) scores. MCS consisted of social functioning, vitality, mental health, and role-emotional scales. MCS score is reported here. MCS domain is scored by summing individual items and transforming scores into a 0 to 100 scale with higher scores indicating better health status or functioning. LS mean was determined by ANCOVA model with variables Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Treatment (Type III sum of squares).

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 52

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

GroupValue (Percentage of HbA1c)Spread
Pooled 5 mg/10 mg/15 mg Tirzepatide-2.260.048
Insulin Lispro-1.160.049
Secondary and other outcome results(7)
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in HbA1c

GroupValue (Percentage of HbA1c)Spread
5 mg Tirzepatide-2.050.082
10 mg Tirzepatide-2.270.083
15 mg Tirzepatide-2.460.084
Insulin Lispro-1.160.049
Secondary outcomeNumber· Week 52

Percentage of Participants With HbA1c Target Values <7.0%

GroupValue (Percentage of participants)
5 mg Tirzepatide61.04
10 mg Tirzepatide75.64
15 mg Tirzepatide79.86
Insulin Lispro36.69
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Body Weight

GroupValue (Kilograms (kg))Spread
5 mg Tirzepatide-6.90.37
10 mg Tirzepatide-9.90.37
15 mg Tirzepatide-12.00.38
Insulin Lispro3.80.22
Secondary outcomeLeast squares mean· Baseline, Week 52

Change From Baseline in Fasting Serum Glucose

GroupValue (milligram per Deciliter (mg/dL))Spread
5 mg Tirzepatide-33.23.28
10 mg Tirzepatide-43.03.32
15 mg Tirzepatide-41.63.42
Insulin Lispro-10.01.99
Secondary outcomeLeast squares mean· Baseline, Week 52

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

GroupValue (mg/dL/day)Spread
5 mg Tirzepatide-56.71.80
10 mg Tirzepatide-61.51.85
15 mg Tirzepatide67.61.86
Insulin Lispro-55.81.13
Secondary outcomeNumber· Week 52

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

GroupValue (Percentage of participants)
5 mg Tirzepatide52.70
10 mg Tirzepatide70.05
15 mg Tirzepatide75.12
Insulin Lispro13.41
Secondary outcomeNumber· Week 52

Percentage of Participants Who Achieved Weight Loss ≥5%

GroupValue (Percentage of participants)
5 mg Tirzepatide64.19
10 mg Tirzepatide79.21
15 mg Tirzepatide83.15
Insulin Lispro6.34

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
5 mg TirzepatideParticipants received 5 mg tirzepatide administered SC once a week.3 / 24320 / 24394 / 243
10 mg TirzepatideParticipants received 10 mg tirzepatide administered SC once a week.3 / 23816 / 238116 / 238
15 mg TirzepatideParticipants received 15 mg tirzepatide administered SC once a week.1 / 23617 / 236121 / 236
Insulin LisproParticipants received Insulin lispro (U100) administered SC three times a day.11 / 70881 / 70899 / 708

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

More studies

2 studies on this page

PubMed tag: none · 2026

Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.

Bajaj et al. 2026Diabetes therapy : research, treatment and education of diabetes and related disorders

PMID 41961454PMC13156352DOI 10.1007/s13300-026-01859-3PUB-41961454

Free to read · publisher termsCC BY-NC
Read at source

Indexing hint: Randomized controlled trial · 2023

Corrected

Tirzepatide vs Insulin Lispro Added to Basal Insulin in Type 2 Diabetes: The SURPASS-6 Randomized Clinical Trial.

Rosenstock et al. 2023JAMAcited by 127

PMID 37786396PMC10548360DOI 10.1001/jama.2023.20294PUB-37786396

Rights unknown
Source linkRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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 \[for participants on metformin, estimated glomerular filtration rate \<45 mL/min/1.73 m2 (or lower than the country-specific threshold for using the protocol-required dose of metformin per local label)\]

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