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Completed

NCT Number: NCT06982846

A 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.

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Key information

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Medizinische Universität Graz

Graz, 8010, Austria

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Retatrutide

Drug

Administered SC

Other names: LY3437943

Placebo

Drug

Administered SC

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 frame: Within 60 minutes after nadir

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

Secondary outcomes

  1. 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 frame: 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.

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

    Time frame: Up to 60 minutes after nadir

    Percentage of participants who require rescue glucose infusion to attain recovery PG concentration of 70 mg/dL.

  3. Hypoglycemic Symptoms Score at set PG Concentration Points

    Time frame: Day 114 during hypoglycemic clamp

    Hypoglycemia symptoms were measured with the Edinburgh Hypoglycemia Symptom Scale (EHSS) where lower scores indicate fewer symptoms.

  4. Percentage of Participants Who Experienced Hypoglycemic Awareness at Set PG Points

    Time frame: Day 114 during hypoglycemic clamp

    Percentage of participants who experienced hypoglycemic awareness at set PG points.

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
May 21, 2025
Registry last updated
Jun 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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