Type 2 Diabetes MellitusPhase 3ENI-SPIRE-2NCT07889648
A Clinical Study to Evaluate the Effects of Enicepatide Versus Tirzepatide in Participants With Type 2 Diabetes and Inadequate Blood Sugar Control on Oral Glucose-Lowering Medications
A Phase 3 study testing Enicepatide and Tirzepatide in people with Type 2 Diabetes Mellitus, run by Hoffmann-La Roche.
Trial summary
The study will evaluate the efficacy and safety of enicepatide, a glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor (GLP-1/GIP) receptor agonist (RA), compared with tirzepatide among participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on oral glucose-lowering… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Enicepatide and Tirzepatide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 948 participants
- Where
- No sites listed yet
- Study dates
- 1 Dec 2026to 23 Apr 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a diagnosis of type 2 diabetes mellitus (T2DM) based on World Health Organization (WHO) classification or other locally applicable diagnostic standards and have inadequate glycemic control in the opinion of the investigator
- Have a HbA1c of ≥7.5% to ≤10.5% (or 58 millimole (mmol)/mol to 91 mmol/mol) at screening
- Receiving stable T2DM treatment with oral glucose-lowering medication, during the 90 days prior to screening, and throughout the screening period until randomization; Dose of oral glucose-lowering medication is considered stable if the dose was unchanged during this 90-day period
- Agree to not initiate a new diet, fast, and/or exercise program during the study which may result in changes in body weight or HbA1c, other than the standard of care lifestyle and dietary measures for diabetes treatment
Who cannot join
- History of type 1 diabetes mellitus (T1DM) diagnosis
- History of ketoacidosis or hyperosmolar state/coma within 12 months prior to screening
- One or more episodes of Level 3 hypoglycemia (per 2026 American Diabetes Association (ADA) Standards of Care in Diabetes) and/or one or more episodes of hypoglycemia unawareness within the 6 months prior to screening
- Self-reported change in body weight of more than 5 kilogram (kg) gain or loss within 90 days prior to screening
- Used any injectable glucose-lowering medication during the 90 days prior to screening, and throughout the screening period until randomization. Short term treatment with insulin for <14 days is permitted for necessary clinical situations
- Body Mass Index (BMI) <25.0 kg/square meter (m2) at screening
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- Estimated glomerular filtration rate (eGFR) <15 milliliters per minute per 1.73 square meters (mL/min/1.73 m2)
- Treatment with any approved, investigational, compounded, or biosimilar versions of GLP-1 RA-based therapy (e.g., GLP-1 receptor agonist, GLP-1/GIP receptor agonist/antagonist, GLP-1/Glucagon receptor agonist, or GLP-1/GIP/Glucagon receptor agonist) or amylin analog within 6 months prior to randomization
- Prior non-response or intolerance to contemporary GLP-1 RA-based therapies
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Reference Study ID Number: WC45975 https://forpatients.roche.com/ No attachments to email below. contact
Fastest response: use the inquiry form. https://www.gene.com/contact-us/submit-medical-inquiry contact
About this study
Official title: A Phase III, Randomized, Open-Label, Active-Controlled Study to Evaluate the Efficacy and Safety of Enicepatide Versus Tirzepatide Among Participants With Type 2 Diabetes and Inadequate Glycemic Control on Oral Glucose-Lowering Medications
The study will evaluate the efficacy and safety of enicepatide, a glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide receptor (GLP-1/GIP) receptor agonist (RA), compared with tirzepatide among participants with type 2 diabetes mellitus (T2DM) and inadequate glycemic control on oral glucose-lowering medications.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Enicepatide, Tirzepatide
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EnicepatideCombination product
Also called RO7795068, RG6640, CT-388
Participants will receive enicepatide as per the schedule described in the protocol.
TirzepatideCombination product
Participants will receive tirzepatide as per the schedule described in the protocol.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: Tirzepatide | Active comparator | Participants will receive tirzepatide. Receives: Combination Product: Tirzepatide |
| Arm 2: Enicepatide | Experimental | Participants will receive enicepatide. Receives: Combination Product: Enicepatide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline to Week 72 in Glycosylated Hemoglobin (HbA1c, %)
Measured: Baseline through Week 72
Secondary outcomes (24)
Percentage of Participants Achieving HbA1c of ≤6.5% at Week 72
Measured: At Week 72
Percentage of Participants Achieving HbA1c of <5.7% at Week 72
Measured: At Week 72
Change From Baseline to Week 72 in Fasting Glucose
Measured: Baseline through Week 72
Percent Change From Baseline to Week 72 in Body Weight
Measured: Baseline through Week 72
Percentage of Participants Achieving HbA1c of <7% at Week 72
Measured: At Week 72
Change From Baseline to Week 72 in 7-Point Self-Monitoring Blood Glucose (SMBG) Profiles
Measured: Baseline through Week 72
Percentage of Participants Achieving HbA1c of <7% at Week 72 Without Clinically Significant, Documented Symptomatic Hypoglycemia, or Severe Hypoglycemia
Measured: At Week 72
Percentage of Participants Achieving HbA1c of <6.5% at Week 72 Without Clinically Significant, Documented Symptomatic Hypoglycemia, or Severe Hypoglycemia
Measured: At Week 72
Percentage of Participants Achieving HbA1c of <5.7% at Week 72 Without Clinically Significant, Documented Symptomatic Hypoglycemia, or Severe Hypoglycemia
Measured: At Week 72
Percentage of Participants Achieving Weight Loss of ≥5% at Week 72
Measured: At Week 72
Percentage of Participants Achieving Weight Loss of ≥10% at Week 72
Measured: At Week 72
Percentage of Participants Achieving Weight Loss of ≥15% at Week 72
Measured: At Week 72
Change From Baseline to Week 72 in Waist Circumference
Measured: Baseline through Week 72
Change From Baseline to Week 72 in Waist-to-Height Ratio
Measured: Baseline through Week 72
Percentage of Participants Achieving HbA1c of ≤6.5% and Weight Loss of ≥10% at Week 72
Measured: At Week 72
Change From Baseline to Week 72 in Total Cholesterol
Measured: Baseline through Week 72
Change from Baseline to Week 72 in Triglycerides
Measured: Baseline through Week 72
Change from Baseline to Week 72 in Low-Density Lipoprotein Cholesterol (LDL-C)
Measured: Baseline through Week 72
Change from Baseline to Week 72 in High-Density Lipoprotein Cholesterol (HDL-C)
Measured: Baseline through Week 72
Change From Baseline to Week 72 in Systolic Blood Pressure
Measured: Baseline through Week 72
Change From Baseline to Week 72 in Diastolic Blood Pressure
Measured: Baseline through Week 72
Change From Baseline to Week 72 in Urine Albumin to Creatinine Ratio (UACR)
Measured: Baseline through Week 72
Change From Baseline to Week 72 in High-Sensitivity C-Reactive Protein (hsCRP)
Measured: Baseline through Week 72
Incidence and Severity of Adverse Events
Measured: From Baseline up to Week 75
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2026
- Study start1 Dec 2026 (estimated)
- Primary completion2 Apr 2029 (estimated)
- Study completion23 Apr 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 948 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Chugai Pharmaceutical
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07889648
- Sponsor's protocol ID
- WC45975
- Other IDs
- 2026-526948-13-00
- Acronym
- ENI-SPIRE-2
- Status last verified
- Oct 2026
- First submitted
- 16 Oct 2026
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing