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.

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.