The Effect of Tirzepatide Versus Dulaglutide on Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes (SURPASS-CVOT)

Official Summary

The purpose of the trial is to assess the efficacy and safety of tirzepatide to dulaglutide in participants with type 2 diabetes and increased cardiovascular risk.

Eligibility Requirements

• Minimum Age: 40 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: DOUBLE
• Enrollment: 13,299 participants

Study Arms

• Tirzepatide (EXPERIMENTAL)
  Tirzepatide administered subcutaneously (SC) once a week.
• Dulaglutide (ACTIVE_COMPARATOR)
  Dulaglutide administered SC once a week.

Interventions

• DRUG: Tirzepatide — Administered SC
• DRUG: Dulaglutide — Administered SC

Primary Outcomes

• Time to First Occurrence of Death from Cardiovascular (CV) Causes, Myocardial Infarction (MI), or Stroke (MACE-3) (Randomization up to Study Completion (Approximate Maximum 54 Months))

Secondary Outcomes

• Time to Death from Any Cause (Randomization up to Study Completion (Approximate Maximum 54 Months))
• Time to CV Death (Randomization up to Study Completion (Approximate Maximum 54 Months))
• Time to First Occurrence of MI (Randomization up to Study Completion (Approximate Maximum 54 Months))
• Time to First Occurrence of Stroke (Randomization up to Study Completion (Approximate Maximum 54 Months))
• Time to First Occurrence of the Expanded Composite of CV Death, MI, Stroke, Coronary Revascularization, or Hospitalization for Unstable Angina (Randomization up to Study Completion (Approximate Maximum 54 Months))

Eligibility Criteria

Inclusion Criteria:

* Men or women at least 40 years old with a diagnosis of type 2 diabetes
* Established cardiovascular disease, including at least 1 of the following:

  * Coronary artery disease (CAD) with any of the following:

    * Documented history of spontaneous myocardial infarction (MI)
    * ≥50% stenosis in 1 or more major coronary arteries, determined by invasive angiography
    * ≥50% stenosis in 2 or more major coronary arteries, determined by computed tomography coronary angiography (CTCA)
    * History of surgical or percutaneous coronary revascularization procedure
  * Cerebrovascular disease - any of the following:

    * Documented history of ischemic stroke
    * Carotid arterial disease with ≥50% stenosis, documented by carotid ultrasound, magnetic resonance imaging (MRI), or angiography
    * Carotid stenting or surgical revascularization
  * Peripheral arterial disease with either of the following:

    * Intermittent claudication and ankle-brachial index \<0.9
    * Prior nontraumatic amputation or peripheral vascular procedure (eg, stenting or surgical revascularization), due to peripheral arterial ischemia
  * Note: Supporting medical documentation is required in all instances
* HbA1c ≥7% (≥53 mmol/mol) and ≤10.5% (≤91.3 mmol/mol) based on central laboratory assessment at screening
* Body mass index (BMI) ≥25 kg/m2
* At the time of signing the informed consent: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical trials.

  * Male patients: Men, regardless of their fertility status, with nonpregnant women of childbearing potential (WOCBP) partners must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms, as well as 1 additional highly effective (less than 1% failure rate) method of contraception (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) or effective method of contraception (such as diaphragms with spermicide or cervical sponges) for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug.

    * Men and their partners may choose to use a double-barrier method of contraception. (Barrier protection methods without concomitant use of a spermicide are not an effective or acceptable method of contraception. Thus, each barrier method must include use of a spermicide. It should be noted, however, that the use of male and female condoms as a double barrier method is not considered acceptable due to the high failure rate when these barrier methods are combined).
    * Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception.
  * Men with pregnant partners should use condoms during intercourse for the duration of the study and until the end of the estimated relevant potential exposure in WOCBP (90 days). Men should refrain from sperm donation for the duration of the study and until their plasma concentrations are below the level that could result in a relevant potential exposure to a possible fetus, predicted to be 90 days following the last dose of study drug. Men who are in exclusively same-sex relationships (as their preferred and usual lifestyle) are not required to use contraception.
  * Female patients: Women of childbearing potential who are abstinent (if this is complete abstinence, as their preferred and usual lifestyle) or in a same-sex relationship (as part of their preferred and usual lifestyle) must agree to either remain abstinent or stay in a same-sex relationship without sexual relationships with males. Periodic abstinence (eg, calendar, ovulation, symptothermal, or postovulation methods), declaration of abstinence just for the duration of a trial, and withdrawal are not acceptable methods of contraception. Otherwise, WOCBP participating must agree to use 2 forms of effective contraception, where at least 1 form is highly effective (less than 1% failure rate), for the entirety of the study. Contraception must continue following completion of study drug administration for the entirety of the study and for 30 days thereafter.

    * WOCBP participating must test negative for pregnancy prior to initiation of treatment as indicated by a negative serum pregnancy test at the screening visit followed by a negative urine pregnancy test within 24 hours prior to exposure.
    * Two forms of effective contraception, where at least 1 form is highly effective, (such as combination oral contraceptives, implanted contraceptives, or intrauterine devices) will be used. Effective contraception (such as male or female condoms with spermicide, diaphragms with spermicide, or cervical sponges) m

Trial Locations

• University of Alabama at Birmingham Medical Center, Birmingham, Alabama, United States
• John Muir Medical Center - Concord Campus, Concord, California, United States
• Valley Clinical Trials, Inc., Covina, California, United States
• AMCR Institute, Escondido, California, United States
• Valley Research, Fresno, California, United States
• NorCal Medical Research, Inc, Greenbrae, California, United States
• UCSD - Altman Clinical and Translational Research Institute (ACTRI), La Jolla, California, United States
• First Valley Medical Group, Lancaster, California, United States
• Monterey Endocrine & Diabetes Institute, Inc., Monterey, California, United States
• Riverside University Health System - Medical Center, Moreno Valley, California, United States
• ...and 10 more locations

Study Officials

• 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) — STUDY_DIRECTOR
  Eli Lilly and Company

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