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

Phase 1

Recruiting

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Retatrutide; Drug: Placebo

• Registration Number: NCT06982846
• Lead Sponsor: Eli Lilly and Company

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-05-14
• Study First Submitted QC: 2025-05-14
• Study First Posted: 2025-05-21
• Study Start: 2025-06-06
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-09
• Last Update Posted: 2025-07-14
• Primary Completion: 2026-05
• Study Completion: 2026-05-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 78

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 allowed oral antihyperglycemic medications (OAMs), 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

  • ≥6.5% and ≤9.5% if on metformin only or
  • ≥6.0% and ≤8.5% if on metformin in combination with allowed OAMs.

• 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Retatrutide	Retatrutide	Participants will receive escalated doses of retatrutide administered subcutaneously (SC) every week (QW) until reaching target dose.
Placebo	Placebo	Participants will receive matching placebo administered SC QW.

Primary Outcome Measures

Name	Time	Method
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)	Within 60 minutes after nadir	Time-to-event of recovery of PG concentration from 48 mg/dL to 70 mg/dL.

Secondary Outcome Measures

Name	Time	Method
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	Time-to-event of recovery of PG concentration from 48 mg/dL to 70 mg/dL including recovery beyond 60 minutes.
Percentage of Participants Who Require Rescue Glucose Infusion to Attain Recovery PG Concentration of 70 mg/dL	Up to 60 minutes after nadir	Percentage of participants who require rescue glucose infusion to attain recovery PG concentration of 70 mg/dL.
Hypoglycemic Symptoms Score at set PG Concentration Points	Day 114 during hypoglycemic clamp	Hypoglycemia symptoms were measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) where lower scores indicate fewer symptoms.
Percentage of Participants Who Experienced Hypoglycemic Awareness at Set PG Points	Day 114 during hypoglycemic clamp	Percentage of participants who experienced hypoglycemic awareness at set PG points.

Trial Locations

Locations (1)

Medizinische Universität Graz; 🇦🇹 Graz, Austria