A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia

NCT06982846 | Active Not Recruiting Phase 1

• 3 other identifiers: 27316J1I-MC-GZQF2024-518471-63-00
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to measure the effect of retatrutide versus placebo, administered every week, on time to recovery from hypoglycemia during hypoglycemic clamp in participants with Type 2 Diabetes Mellitus (T2DM) following 16 weeks of treatment.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Time-to-Event of Recovery of Plasma Glucose (PG) Concentration from 48 Milligram per Deciliter (48 mg/dL) to 70 mg/dL (tPG_nadir-70 mg/dL)

  Time-to-event of recovery of PG concentration from 48 mg/dL to 70 mg/dL.

  Within 60 minutes after nadir

Secondary Outcomes (4)

• Time to Reach Recovery of Plasma Glucose (PG) Concentration from 48 mg/dL to 70 mg/dL (tPG_nadir-70 mg/dL) Including Recovery Beyond 60 Minutes.

  Beyond 60 minutes after nadir

• Percentage of Participants Who Require Rescue Glucose Infusion to Attain Recovery PG Concentration of 70 mg/dL

  Up to 60 minutes after nadir

• Hypoglycemic Symptoms Score at set PG Concentration Points

  Day 114 during hypoglycemic clamp

• Percentage of Participants Who Experienced Hypoglycemic Awareness at Set PG Points

  Day 114 during hypoglycemic clamp

Study Arms (2)

Retatrutide

EXPERIMENTAL

Participants will receive escalated doses of retatrutide administered subcutaneously (SC) every week (QW) until reaching target dose.

Drug: Retatrutide

Placebo

PLACEBO COMPARATOR

Participants will receive matching placebo administered SC QW.

Drug: Placebo

Interventions

Retatrutide DRUG

Administered SC

Also known as: LY3437943

Retatrutide

Placebo DRUG

Administered SC

Placebo

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 T2DM for at least 6 months prior to screening.
• Treated with diet and exercise and stable treatment with metformin with or without 1 additional allowed oral antihyperglycemic medications (OAM), 3 months prior to screening.
• Treatment with metformin will be considered stable if all prescribed total daily doses for this period were ±850 mg from the original prescription for the same participant.
• Allowed OAMs include dipeptidyl peptidase-4 (DPP-IV) inhibitors, sodium-glucose co-transporter-2 (SGLT2) inhibitors, glinides, or sulfonylureas.
• Have a hemoglobin A1c value at screening of
• ≥6.0% (≥ 42 millimole per liter(mmol/L)) and ≤9.5% (≤80 mmol/L) if on metformin only or
• ≥6.0% (≥42 mmol/L) and ≤8.5% (≤69 mmol/L) if on metformin in combination with 1 additional allowed OAM.
• Have a BMI within the range 25.0 kg/m2 and 45.0 kg/m2 kg/m2 (both inclusive).
• Have had a stable body weight that is less than 5% change in body weight for more than 3 months prior to screening.

You may not qualify if:

• Have Type 1 diabetes mellitus.
• Have had more than 1 episode of severe hypoglycemia, as defined by the American Diabetes Association criteria, within 6 months before screening or has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms.
• Have had 1 or more episodes of ketoacidosis or hyperosmolar state/coma requiring hospitalization within the 6 months prior to screening.
• Have impaired renal estimated glomerular filtration rate \<60 mL/min/1.73 m2 calculated by Chronic Kidney Disease-Epidemiology.
• Have acute or chronic pancreatitis or a history of acute idiopathic pancreatitis.
• Have elevations in
• serum aspartate aminotransferase (AST) \>2.5× upper limit normal (ULN)
• serum alanine aminotransferase (ALT) \>2.5×ULN
• total bilirubin level (TBL) \>1.5×ULN, or
• alkaline phosphatase (ALP) level ≥1.5× ULN.
• Have a known clinically significant gastric emptying abnormality.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (1)

Medizinische Universität Graz

Graz, 8010, Austria

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

retatrutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor-blind
• 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 6, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: January 20, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)