Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03730662




Registration number
NCT03730662
Ethics application status
Date submitted
2/11/2018
Date registered
5/11/2018
Date last updated
14/02/2022

Titles & IDs
Public title
A Study of Tirzepatide (LY3298176) Once a Week Versus Insulin Glargine Once a Day in Participants With Type 2 Diabetes and Increased Cardiovascular Risk
Scientific title
Efficacy and Safety of LY3298176 Once Weekly Versus Insulin Glargine in Patients With Type 2 Diabetes and Increased Cardiovascular Risk (SURPASS-4)
Secondary ID [1] 0 0
I8F-MC-GPGM
Secondary ID [2] 0 0
17072
Universal Trial Number (UTN)
Trial acronym
SURPASS-4
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 2 Diabetes Mellitus 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tirzepatide
Treatment: Drugs - Insulin Glargine

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 Glargine - Insulin glargine administered SC once a day. Doses were individualized and titrated according to protocol-defined targets.

The starting dose of insulin glargine was 10 IU/day at bedtime, titrated to a FBG \<100 mg/dL, following a treat-to-target (TTT) algorithm.


Treatment: Drugs: Tirzepatide
Administered SC.

Treatment: Drugs: Insulin Glargine
Administered SC
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [1] 0 0
Change From Baseline in HbA1c (5 mg)
Timepoint [1] 0 0
Baseline, Week 52
Secondary outcome [2] 0 0
Change From Baseline in Body Weight
Timepoint [2] 0 0
Baseline, Week 52
Secondary outcome [3] 0 0
Percentage of Participants With HbA1c of <7.0%
Timepoint [3] 0 0
Week 52
Secondary outcome [4] 0 0
Change From Baseline in Fasting Serum Glucose
Timepoint [4] 0 0
Baseline, Week 52
Secondary outcome [5] 0 0
Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) Values
Timepoint [5] 0 0
Baseline, Week 52
Secondary outcome [6] 0 0
Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve From Zero to Tau (AUC 0-Tau) of Tirzepatide
Timepoint [6] 0 0
1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post dose of Week 7, 15, 23, 35
Secondary outcome [7] 0 0
Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 (Millimole/Liter (mmol/L))] or Severe Hypoglycemia
Timepoint [7] 0 0
Baseline through Week 52

Eligibility
Key inclusion criteria
Participants must:

* Have been diagnosed with type 2 diabetes mellitus (T2DM)
* Have HbA1c between =7.5% and =10.5%
* Be on stable treatment with unchanged dose of at least 1 and no more than 3 types of oral antihyperglycemic drugs, which may only include metformin, SGLT-2 inhibitors, and/or sulfonylureas for at least 3 months before screening
* Have increased risk for cardiovascular (CV) events
* Be of stable weight (± 5%)
* Have a BMI =25 kilograms per meter squared (kg/m2) at screening
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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 immediate or urgent 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 there ALT level is =3.0 the ULN for the reference range
* 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, SGLT-2 inhibitors, and/or sulfonylureas during the last 3 months
* Have been taking weight loss drugs, including over-the-counter medications during the last 3 months

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/11/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
22/04/2021
Sample size
Target
Accrual to date
Final
2002
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Paratus Clinical Blacktown Clinic - Blacktown
Recruitment hospital [2] 0 0
Campbelltown Medical & Dental Centre - Campbelltown
Recruitment hospital [3] 0 0
Paratus Clinical Kanwal Clinic - Kanwal
Recruitment hospital [4] 0 0
The AIM Centre - Merewether
Recruitment hospital [5] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [6] 0 0
CORE Research Group Pty Ltd - Brisbane
Recruitment hospital [7] 0 0
Morayfield Medical and Dental Centre - Morayfield
Recruitment hospital [8] 0 0
AusTrials Pty Ltd - Sherwood
Recruitment hospital [9] 0 0
Victoria Point Medical and Dental Centre - Victoria Point
Recruitment hospital [10] 0 0
GP Plus Marion - Oaklands Park
Recruitment hospital [11] 0 0
Eastern Clinical Research Unit - Box Hill
Recruitment hospital [12] 0 0
Forest Hill Medical and Dental Centre - Forest Hill
Recruitment hospital [13] 0 0
Barwon Health - The Geelong Hospital - Geelong
Recruitment hospital [14] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [15] 0 0
Fremantle Hospital - Fremantle
Recruitment postcode(s) [1] 0 0
2148 - Blacktown
Recruitment postcode(s) [2] 0 0
2560 - Campbelltown
Recruitment postcode(s) [3] 0 0
2259 - Kanwal
Recruitment postcode(s) [4] 0 0
2291 - Merewether
Recruitment postcode(s) [5] 0 0
2065 - St. Leonards
Recruitment postcode(s) [6] 0 0
4064 - Brisbane
Recruitment postcode(s) [7] 0 0
4506 - Morayfield
Recruitment postcode(s) [8] 0 0
4075 - Sherwood
Recruitment postcode(s) [9] 0 0
4165 - Victoria Point
Recruitment postcode(s) [10] 0 0
5046 - Oaklands Park
Recruitment postcode(s) [11] 0 0
3128 - Box Hill
Recruitment postcode(s) [12] 0 0
3131 - Forest Hill
Recruitment postcode(s) [13] 0 0
3220 - Geelong
Recruitment postcode(s) [14] 0 0
3050 - Parkville
Recruitment postcode(s) [15] 0 0
6160 - Fremantle
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Idaho
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Iowa
Country [8] 0 0
United States of America
State/province [8] 0 0
Kansas
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Montana
Country [14] 0 0
United States of America
State/province [14] 0 0
Nevada
Country [15] 0 0
United States of America
State/province [15] 0 0
New Hampshire
Country [16] 0 0
United States of America
State/province [16] 0 0
North Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
North Dakota
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oklahoma
Country [20] 0 0
United States of America
State/province [20] 0 0
Oregon
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
South Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Utah
Country [26] 0 0
United States of America
State/province [26] 0 0
Virginia
Country [27] 0 0
United States of America
State/province [27] 0 0
Washington
Country [28] 0 0
Argentina
State/province [28] 0 0
Buenos Aires
Country [29] 0 0
Argentina
State/province [29] 0 0
Mendoza
Country [30] 0 0
Argentina
State/province [30] 0 0
Ciudad Autonoma de Buenos Aire
Country [31] 0 0
Argentina
State/province [31] 0 0
Cordoba
Country [32] 0 0
Brazil
State/province [32] 0 0
Ceara
Country [33] 0 0
Brazil
State/province [33] 0 0
Distrito Federal
Country [34] 0 0
Brazil
State/province [34] 0 0
ES
Country [35] 0 0
Brazil
State/province [35] 0 0
Parana
Country [36] 0 0
Brazil
State/province [36] 0 0
RJ
Country [37] 0 0
Brazil
State/province [37] 0 0
SP
Country [38] 0 0
Brazil
State/province [38] 0 0
Fortaleza
Country [39] 0 0
Brazil
State/province [39] 0 0
São Paulo
Country [40] 0 0
Canada
State/province [40] 0 0
Alberta
Country [41] 0 0
Canada
State/province [41] 0 0
Ontario
Country [42] 0 0
Canada
State/province [42] 0 0
Quebec
Country [43] 0 0
Greece
State/province [43] 0 0
Athens
Country [44] 0 0
Greece
State/province [44] 0 0
Thessaloniki
Country [45] 0 0
Greece
State/province [45] 0 0
Larissa
Country [46] 0 0
Israel
State/province [46] 0 0
Afula
Country [47] 0 0
Israel
State/province [47] 0 0
Beer Sheva
Country [48] 0 0
Israel
State/province [48] 0 0
Haifa
Country [49] 0 0
Israel
State/province [49] 0 0
Holon
Country [50] 0 0
Israel
State/province [50] 0 0
Jerusalem
Country [51] 0 0
Israel
State/province [51] 0 0
Petach Tikva
Country [52] 0 0
Israel
State/province [52] 0 0
Ramat Gan
Country [53] 0 0
Israel
State/province [53] 0 0
Sakhnin
Country [54] 0 0
Israel
State/province [54] 0 0
Tel Aviv Jaffa
Country [55] 0 0
Mexico
State/province [55] 0 0
Jalisco
Country [56] 0 0
Mexico
State/province [56] 0 0
Mexico State
Country [57] 0 0
Mexico
State/province [57] 0 0
Nuevo León
Country [58] 0 0
Mexico
State/province [58] 0 0
Tamaulipas
Country [59] 0 0
Mexico
State/province [59] 0 0
Chihuahua
Country [60] 0 0
Poland
State/province [60] 0 0
Mazowieckie
Country [61] 0 0
Poland
State/province [61] 0 0
Bialystok
Country [62] 0 0
Poland
State/province [62] 0 0
Krakow
Country [63] 0 0
Poland
State/province [63] 0 0
Lodz
Country [64] 0 0
Poland
State/province [64] 0 0
Lublin
Country [65] 0 0
Poland
State/province [65] 0 0
Poznan
Country [66] 0 0
Poland
State/province [66] 0 0
Ruda Slaska
Country [67] 0 0
Poland
State/province [67] 0 0
Wroclaw
Country [68] 0 0
Puerto Rico
State/province [68] 0 0
Arecibo
Country [69] 0 0
Puerto Rico
State/province [69] 0 0
Manati
Country [70] 0 0
Puerto Rico
State/province [70] 0 0
Ponce
Country [71] 0 0
Puerto Rico
State/province [71] 0 0
Rio Pedras
Country [72] 0 0
Puerto Rico
State/province [72] 0 0
San Juan
Country [73] 0 0
Romania
State/province [73] 0 0
Constanta
Country [74] 0 0
Romania
State/province [74] 0 0
Jud Satu-Mare
Country [75] 0 0
Romania
State/province [75] 0 0
Maramures
Country [76] 0 0
Romania
State/province [76] 0 0
Mures
Country [77] 0 0
Romania
State/province [77] 0 0
Timis
Country [78] 0 0
Romania
State/province [78] 0 0
Brasov
Country [79] 0 0
Romania
State/province [79] 0 0
Bucharest
Country [80] 0 0
Romania
State/province [80] 0 0
Bucuresti
Country [81] 0 0
Romania
State/province [81] 0 0
Galati
Country [82] 0 0
Russian Federation
State/province [82] 0 0
Arkhangelsk
Country [83] 0 0
Russian Federation
State/province [83] 0 0
Moscow
Country [84] 0 0
Russian Federation
State/province [84] 0 0
Novosibirsk
Country [85] 0 0
Russian Federation
State/province [85] 0 0
Ryazan
Country [86] 0 0
Russian Federation
State/province [86] 0 0
Saint Petersburg
Country [87] 0 0
Russian Federation
State/province [87] 0 0
Saint-Petersburg
Country [88] 0 0
Russian Federation
State/province [88] 0 0
Saratov
Country [89] 0 0
Russian Federation
State/province [89] 0 0
Yaroslavl
Country [90] 0 0
Slovakia
State/province [90] 0 0
Slovak Republic
Country [91] 0 0
Slovakia
State/province [91] 0 0
Puchov
Country [92] 0 0
Slovakia
State/province [92] 0 0
Roznava
Country [93] 0 0
Slovakia
State/province [93] 0 0
Sabinov
Country [94] 0 0
Spain
State/province [94] 0 0
Cantabria
Country [95] 0 0
Spain
State/province [95] 0 0
Madrid
Country [96] 0 0
Spain
State/province [96] 0 0
Valencia
Country [97] 0 0
Spain
State/province [97] 0 0
Alicante
Country [98] 0 0
Spain
State/province [98] 0 0
Almeria
Country [99] 0 0
Spain
State/province [99] 0 0
Barcelona
Country [100] 0 0
Spain
State/province [100] 0 0
Granada
Country [101] 0 0
Spain
State/province [101] 0 0
La Coruña
Country [102] 0 0
Spain
State/province [102] 0 0
Malaga
Country [103] 0 0
Spain
State/province [103] 0 0
Palma de Mallorca
Country [104] 0 0
Spain
State/province [104] 0 0
Sevilla
Country [105] 0 0
Spain
State/province [105] 0 0
Seville
Country [106] 0 0
Taiwan
State/province [106] 0 0
Taipei County
Country [107] 0 0
Taiwan
State/province [107] 0 0
Kaohsiung City
Country [108] 0 0
Taiwan
State/province [108] 0 0
Taichung City
Country [109] 0 0
Taiwan
State/province [109] 0 0
Taichung County
Country [110] 0 0
Taiwan
State/province [110] 0 0
Taichung
Country [111] 0 0
Taiwan
State/province [111] 0 0
Tainan City
Country [112] 0 0
Taiwan
State/province [112] 0 0
Tainan
Country [113] 0 0
Taiwan
State/province [113] 0 0
Taipei City
Country [114] 0 0
Taiwan
State/province [114] 0 0
Taipei

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Eli Lilly and Company
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of the trial is to assess the efficacy and safety of tirzepatide taken once a week to insulin glargine taken once daily in participants with type 2 diabetes and increased cardiovascular risk. The study will last about 108 weeks and may include up to 30 visits.
Trial website
https://clinicaltrials.gov/study/NCT03730662
Trial related presentations / publications
Heerspink HJL, Sattar N, Pavo I, Haupt A, Duffin KL, Yang Z, Wiese RJ, Tuttle KR, Cherney DZI. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 Nov;10(11):774-785. doi: 10.1016/S2213-8587(22)00243-1. Epub 2022 Sep 21.
Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese RJ, Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022 Mar;28(3):591-598. doi: 10.1038/s41591-022-01707-4. Epub 2022 Feb 24.
Del Prato S, Kahn SE, Pavo I, Weerakkody GJ, Yang Z, Doupis J, Aizenberg D, Wynne AG, Riesmeyer JS, Heine RJ, Wiese RJ; SURPASS-4 Investigators. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 2021 Nov 13;398(10313):1811-1824. doi: 10.1016/S0140-6736(21)02188-7. Epub 2021 Oct 18.
Public notes

Contacts
Principal investigator
Name 0 0
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT03730662