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

A Randomized, Placebo-Controlled, Parallel Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Retatrutide

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 1

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Medizinische Universität Graz

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Retatrutide; Participants will receive escalated doses of retatrutide administered subcutaneously (SC) every week (QW) until reaching target dose.	Drug: Retatrutide; Administered SC; Other Names: LY3437943
Placebo Comparator: Placebo; Participants will receive matching placebo administered SC QW.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Time-to-event of recovery of PG concentration from 48 mg/dL to 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	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	Hypoglycemia symptoms were measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) where lower scores indicate fewer symptoms.	Day 114 during hypoglycemic clamp
Percentage of Participants Who Experienced Hypoglycemic Awareness at Set PG Points	Percentage of participants who experienced hypoglycemic awareness at set PG points.	Day 114 during hypoglycemic clamp

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: 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 record dates

Study Major Dates

• Study Start (Actual): June 6, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: May 14, 2025
• First Submitted That Met QC Criteria: May 14, 2025
• First Posted (Actual): May 21, 2025

Study Record Updates

• Last Update Posted (Actual): January 20, 2026
• Last Update Submitted That Met QC Criteria: January 16, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; retatrutide
• Other Study ID Numbers: 27316; J1I-MC-GZQF (Other Identifier: Eli Lilly and Company); 2024-518471-63-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No