A Study of Enicepatide (CT-388) in Participants Who Are Overweight or Obese With Type 2 Diabetes Mellitus

• Placebo (Drug): Placebo will be volume-matched and administered subcutaneously (SC) once weekly.
• Enicepatide (Drug), also known as CT-388, RO7795068, RG6640: Enicepatide will be administered subcutaneously (SC) once weekly at the randomized dosing regimen.

Primary outcomes

• Percent Change in Body Weight from Baseline to Week 36 [Baseline to Week 36]
• Change in Glycated Hemoglobin (HbA1c) from Baseline to Week 36 [Baseline to Week 36]

Secondary outcomes

• Percent Change in Body Weight from Baseline to Week 48 [Baseline to Week 48]
• Change in HbA1c from Baseline to Week 48 [Baseline to Week 48]
• Percentage of Participants with HbA1c <7.0% at Weeks 36 and 48 [Weeks 36 and 48]
• Percentage of Participants with Body Weight Reduction ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from Baseline to Week 36 [Baseline and Week 36]
• Percentage of Participants with Body Weight Reduction ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from Baseline to Week 48 [Baseline and Week 48]
• Percent Change in Body Weight from Baseline to Week 28 [Baseline and Week 28]
• Absolute Change in Body Weight (kg) from Baseline to Weeks 36 and 48 [Baseline to Weeks 36 and 48]
• Percent Change in Body Weight from Baseline to Weeks 16, 28, 36, and 48 by Obesity Class [Baseline to Weeks 16, 28, 36, and 48]
• Change in HbA1c from Baseline to Weeks 16 and 28 [Baseline to Weeks 16 and 28]
• Change in HbA1c from Baseline to Weeks 16, 28, 36, and 48 by Obesity Class [Baseline to Weeks 16, 28, 36, and 48]
• Percentage of Participants with HbA1c ≤6.5% at Weeks 16, 28, 36, and 48 [Weeks 16, 28, 36, and 48]
• Percentage of Participants with HbA1c <5.7% at Weeks 16, 28, 36, and 48 [Weeks 16, 28, 36, and 48]
• Change in 7-point Self-Monitored Blood Glucose (SMBG) Profile at Weeks 16, 28, 36, and 48 [Weeks 16, 28, 36, and 48]
• Percentage of Participants who Achieve HbA1c ≤6.5% and ≥10.0% Weight Reduction at Weeks 16, 28, 36, and 48 [Baseline, Weeks 16, 28, 36, and 48]
• Percentage of Participants who Achieve HbA1c <7.0% and ≥5.0% Weight Reduction at Weeks 16, 28, 36, and 48 [Baseline, Weeks 16, 28, 36, and 48]
• Change in Body Mass Index (BMI) from Baseline to Weeks 36 and 48 [Baseline, Weeks 36 and 48]
• Change in Waist Circumference from Baseline to Weeks 36 and 48 [Baseline, Weeks 36 and 48]
• Change in Hip Circumference from Baseline to Weeks 36 and 48 [Baseline, Weeks 36 and 48]
• Change in Waist-to-Hip Ratio from Baseline to Weeks 36 and 48 [Baseline, Weeks 36 and 48]
• Change in Waist-to-Height Ratio from Baseline to Weeks 36 and 48 [Baseline, Weeks 36 and 48]
• Change in Fasting Plasma Glucose from Baseline to Weeks 16, 28, 36, and 48 [Baseline to Weeks 16, 28, 36, and 48]
• Change in Fasting Insulin from Baseline to Weeks 16, 28, 36, and 48 [Baseline to Weeks 16, 28, 36, and 48]
• Change in Fasting C-peptide from Baseline to Weeks 16, 28, 36, and 48 [Baseline to Weeks 16, 28, 36, and 48]
• Change in Fasting Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) from Baseline to Weeks 16, 28, 36, and 48 [Baseline to Weeks 16, 28, 36, and 48]

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Male or female, 18 to 75 years of age
* Body mass index (BMI) ≥25.0 kg/m\^2
* Have a diagnosis of Type 2 Diabetes Mellitus (T2DM) according to the World Health Organization classification or other locally applicable standards
* Have an HbA1c ≥7% and ≤10.5%
* Management of T2DM with diet and exercise alone, metformin, or a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, as monotherapy or in combination, per approved local label
* At least one self-reported unsuccessful diet/exercise effort to lose body weight

Exclusion Criteria:

* Have Type 1 Diabetes Mellitus (T1DM), history of ketosis or hyperosmolar state/coma, or any other types of diabetes except T2DM
* Have had 1 or more episodes of Level 3 hypoglycemia or have had hypoglycemia unawareness within 3 months prior to screening
* Have history or presence of proliferative diabetic retinopathy, diabetic macular edema, or non-proliferative diabetic retinopathy that requires acute treatment
* Have evidence of clinically significant autonomic neuropathy (symptoms may include resting tachycardia, orthostatic hypotension, or diabetic diarrhea)
* Had treatment with any oral antihyperglycemic medications, with the exception of metformin or SGLT-2 inhibitors, within 3 months prior to screening or planned concurrent treatment with these medications during the study
* Had treatment with injectable antihyperglycemic medication, with the exception of short-term insulin, within 6 months prior to screening or planned concurrent treatment with these medications during the study
* Self-reported body weight change of >5 kg within 3 months before screening
* Any unbalanced/extreme diets, such as very low calorie, low carbohydrate, very high protein, ketogenic, or intermittent diets, within 3 months of the screening visit, or plan to be on such diets during the study
* Current or recent use of any treatment that promotes weight loss or glucose metabolism
* Current or recent use of treatment that may cause weight gain
* Prior or planned surgical treatment or procedure for obesity, except for liposuction or abdominoplasty if performed >1 year prior to screening. Participants with a history of devices, such as LAP-BAND® or intragastric balloon, are permitted, if devices were removed >1 year prior to screening.
* History of clinically significant or active gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction, intestinal obstruction), or chronic use of medications that directly affect GI motility
* History of chronic pancreatitis or acute pancreatitis or have signs and symptoms of acute pancreatitis at screening
* Have obesity induced by other endocrinologic disorders (e.g., Cushing syndrome) or diagnosed monogenetic or syndromic forms of obesity
* History or diagnosis of significant active or unstable major depressive disorder or any history/diagnosis of other severe psychiatric conditions (e.g., schizophrenia; bipolar disorder; other serious mood disorder or anxiety disorder, or hyperactivity disorder) within the last year before screening
* History of any hematologic conditions that may interfere with HbA1c measurement (e.g., hemolytic anemias, sickle cell disease, other hemoglobinopathies)
* Family or personal history of medullary thyroid carcinoma
* Women who are pregnant, breastfeeding, or intend to become pregnant, or are of childbearing potential and not using a highly effective contraceptive method as required per protocol

• Clinical Trials, Study director, Carmot Therapeutics, Inc., a Member of the Roche Group