A Study to Evaluate the Effect of Retatrutide on Insulin Secretion and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus

NCT06982859 | Recruiting Phase 1

• 3 other identifiers: 27317J1I-MC-GZQG2024-518470-13-00
• Study Type: interventional
• Target: 95
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of Study GZQG is to compare the effect of retatrutide and placebo on total clamp disposition index (cDI) after 28 weeks of treatment.

Conditions

Diabetes Mellitus; Insulin Sensitivity

Outcome Measures

Primary Outcomes (1)

• Change from Baseline in Total Clamp Disposition Index (cDI) for Comparison of Retatrutide With Placebo

  Change from baseline in total cDI for comparison of retatrutide with placebo

  Baseline, Week 28

Secondary Outcomes (12)

• Change from Baseline in cDI for Comparison Between Retatrutide and Semaglutide

  Baseline, Week 28

• Change from Baseline in Hyperinsulinemic Euglycemic Clamp M-value

  Baseline, Week 28

• Change from Baseline in First Phase Incremental Insulin Secretion Rate (ISR)

  Baseline, Week 28

• Change from Baseline in Second Phase Total ISR

  Baseline, Week 28

• Change from Baseline in Total ISR

  Baseline, Week 28

Study Arms (3)

Retatrutide

EXPERIMENTAL

Retatrutide administered subcutaneously (SC).

Drug: Retatrutide

Semaglutide

ACTIVE COMPARATOR

Semaglutide administered SC.

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

Placebo administered SC.

Drug: Placebo

Interventions

Semaglutide DRUG

Administered SC

Semaglutide

Placebo DRUG

Administered SC

Placebo

Retatrutide DRUG

Administered SC

Also known as: LY3437943

Retatrutide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have been diagnosed with Type 2 Diabetes Mellitus (T2DM) for at least 6 months prior to screening.
• Treated with diet and exercise and metformin daily, with or without other allowed oral antihyperglycaemia medications (OAMs), 3 months prior to screening. Allowed OAMs are dipeptidyl peptidase-4 inhibitors (DPP-IV) inhibitors, sodium/glucose cotransporter 2 (SGLT2) inhibitors, glinides, and sulfonylureas.
• Have a HbA1c value at screening of:
• % and ≤ 9.5 % if on metformin with or without SGLT2 inhibitors, or
• % and ≤8.5% if on metformin in combination with allowed OAMs that require washout.
• Have venous access sufficient to allow for blood sampling as per the protocol.
• Have clinical laboratory test results within normal reference range for the population or investigative site or results with acceptable deviations that are judged to be not clinically significant by the investigator.
• Have a body mass index (BMI) between 25 kilograms per meter squared (kg/m²) and 45 kg/m², both inclusive, at screening.
• Have had a stable body weight that is less than 5% change during the 3-month period prior to screening.

You may not qualify if:

• Have Type 1 Diabetes Mellitus (T1DM)
• Have had more than 1 episode of severe hypoglycaemia, as defined by the American Diabetes Association criteria, within 6 months before screening or a history of hypoglycaemia unawareness or poor recognition of hypoglycaemic symptoms; any participant that cannot communicate an understanding of hypoglycaemic symptoms and the appropriate treatment of hypoglycaemia prior to the first dose of study drug should also be excluded.
• Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiring hospitalisation within the 6 months prior to screening.
• Are currently receiving, planning to receive, or in need of treatment, that is, intravitreal injections of Vascular Endothelial Growth Factor inhibitor or corticosteroids, focal/grid macular laser surgery, panretinal photocoagulation, or vitrectomy for diabetic retinopathy at screening.
• Have impaired renal estimated glomerular filtration rate \<60.0 mL/min/1.73 m² calculated by Chronic Kidney Disease-Epidemiology (2021).
• Have acute or chronic pancreatitis or a history of acute idiopathic pancreatitis.
• Have elevations in:
• serum aspartate aminotransferase (AST) \>2.5X the upper limit of normal (ULN)
• serum alanine aminotransferase (ALT) \>2.5X ULN
• total bilirubin level (TBL) \>1.5X ULN (except, participants with Gilbert's syndrome), or
• Alkaline phosphatase (ALP) level ≥1.5X ULN
• Show evidence of possible chronic or active hepatitis B, including hepatitis B core antibody and/or hepatitis B surface antigen positivity.
• Have a positive Hepatitis C virus (HCV) antibody (Ab) test. Participants with a positive HCV Ab test at screening can be included only if a confirmatory HCV ribonucleic acid (RNA) test is negative.
• Have a known clinically significant gastric emptying abnormality, have undergone gastric bypass (bariatric) surgery or restrictive bariatric surgery or chronically take drugs that directly affect GI motility.
• Have had within 3 months prior to screening:

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Profil Institut für Stoffwechselforschung

Neuss, 41460, Germany

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

retatrutide; semaglutide

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Central Study Contacts

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor is blinded to Retatrutide/Placebo. Semaglutide is open-label.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 21, 2025
• Study Start: June 2, 2025
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: March 3, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)