A Research Study Comparing How Well Different Doses of the Medicine UBT251 Lower Blood Sugar in People With Type 2 Diabetes

• UBT251 (Drug): UBT251 will be administered subcutaneously once-weekly.
• UBT251 Placebo (Drug): UBT251 placebo will be administered subcutaneously once-weekly.
• Semaglutide (Drug): Semaglutide will be administered subcutaneously once-weekly.
• Semaglutide Placebo (Drug): Semaglutide placebo will be administered subcutaneously once-weekly.

Primary outcomes

• UBT251: Change in glycated haemoglobin (HbA1c) [From baseline (week 0) to 12 weeks on a given maintenance dose (week 16, 28 and 40)]: Measured as percentage (%)-point.

Secondary outcomes

• UBT251: Relative change in body weight [From baseline (week 0) to week 40]: Measured as %.
• UBT251: Change in body weight [From baseline (week 0) to week 40]: Measured as kilogram (kg).
• UBT251 vs placebo: Change in HbA1c [From baseline (week 0) to 12 weeks on a given maintenance dose (week 16, 28 and 40)]: Measured as %-point.
• Change in HbA1c [From baseline (week 0) to week 40]: Measured as %-point.
• Change in homeostasis model assessment of insulin resistance (HOMA2-IR) [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in homeostasis model assessment of beta-cell function (HOMA2-B) [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in fasting plasma glucose (FPG) [From baseline (week 0) to 12 weeks on a given maintenance dose (week 16, 28 and 40)]: Measured as millimoles per litre (mmol/L).
• CGM: Change in time in range (TIR) 3.9-10.0 mmol/L (70-180 milligrams per deciliter (mg/dL)) [From baseline (week -2 to week 0) to week 14- 16, week 26-28 and week 38-40, respectively]: Measured as %-points.
• UBT251 vs placebo: Relative change in body weight [From baseline (week 0) to week 40]: Measured as %.
• UBT251 vs placebo: Change in body weight [From baseline (week 0) to week 40]: Measured as kg.
• Change in body mass index (BMI) [From baseline (week 0) to week 40]: Measured as Kilograms per square meter (kg/m\^2).
• Change in waist circumference [From baseline (week 0) to week 40]: Measured as centimeter (cm).
• Change in waist-to-height ratio (WHtR) [From baseline (week 0) to week 40]
• Change in systolic blood pressure (SBP) [From baseline (week 0) to week 40]: Measured as millimetres of mercury (mmHg).
• Change in diastolic blood pressure (DBP) [From baseline (week 0) to week 40]: Measured as mmHg.
• Change in pulse rate [From baseline (week 0) to week 40]: Measured in beats/min.
• Change in high sensitivity C-Reactive Protein (hsCRP) [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in total cholesterol [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in high-density lipoprotein (HDL) cholesterol [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in low-density lipoprotein (LDL) cholesterol [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in triglycerides [From baseline (week 0) to week 40]: Measured as ratio to baseline.
• Change in urine albumin creatinine ratio (UACR) [From baseline (week 0) to 12 weeks on a given maintenance dose (week 16, 28 and 40)]: Measured as ratio to baseline.
• Change in eGFR (creatinine-cystatin C-based CKD-EPI 2021) [From baseline (week 0) to week 40]: Measured in milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2).
• Number of treatment-emergent adverse events (TEAEs) [From baseline (week 0) to week 46]: Measured as number of events.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* Male or female (sex assigned at birth, inclusive of all gender identities).
* Age 18-75 years (both inclusive) at the time of signing the informed consent.
* Diagnosed with type 2 diabetes greater than or equal to (≥) 180 days before screening.
* Stable daily dose(s) ≥ 90 days before screening of the following antidiabetic drug(s) or combination regimen(s) at effective or maximum tolerated dose as judged by the investigator:

metformin with or without sodium-glucose cotransporter-2 (SGLT2) inhibitor.

* HbA1c of 7.0-10.5 percent (%) (53-91 millimoles per mole (mmol/mol)) (both inclusive) as assessed by central laboratory at screening.
* Body mass index between 25.0 kg/m\^2 and 50.0 kg/m\^2 (both inclusive) at screening.

Exclusion Criteria:

* Treatment with any medication (prescription or over-the counter) or alternative remedies for the indication of diabetes or obesity other than stated in the inclusion criteria within 90 days before screening. However, short term insulin treatment for a maximum of 14 consecutive days and prior insulin treatment for gestational diabetes are allowed.
* Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by an eye examination performed within 90 days before screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.
* Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire, question 8.

• Clinical Transparency dept. 2834, Study director, Novo Nordisk A/S