Clinical trial NCT06982846: A Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia
Official title: A Randomized, Placebo-Controlled, Parallel Study to Investigate the Response of Participants With Type 2 Diabetes Mellitus on Once-Weekly Retatrutide to Hypoglycemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2025-05-21
Enrollment: 78
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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)
timeFrame: Within 60 minutes after nadir
Secondary outcomes:
measure: 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.
timeFrame: Beyond 60 minutes after nadir
measure: Percentage of Participants Who Require Rescue Glucose Infusion to Attain Recovery PG Concentration of 70 mg/dL
timeFrame: Up to 60 minutes after nadir
measure: Hypoglycemic Symptoms Score at set PG Concentration Points
timeFrame: Day 114 during hypoglycemic clamp
measure: Percentage of Participants Who Experienced Hypoglycemic Awareness at Set PG Points
timeFrame: Day 114 during hypoglycemic clamp
Other outcomes:
Locations:
city: Graz
country: Austria
facility: Medizinische Universität Graz
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: