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

Registered clinical trial record on ClinicalTrials.gov (NCT06982846). This describes a planned, ongoing, or completed study — it is NOT peer-reviewed results. Status: completed. Study type: interventional. Phase: Phase 1. Sponsor: Eli Lilly and Company. Conditions: Type 2 Diabetes Mellitus. Interventions: Retatrutide, Placebo. 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. Primary outcome measures: 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). Eligibility: 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.