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.

Sponsor-blind