A Research Study to Investigate the Effects of CagriSema Compared to Placebo in People With Type 2 Diabetes and Painful Diabetic Peripheral Neuropathy

Key Inclusion Criteria:

• Male or female.

• Age 18 years or above at the time of signing the informed consent.

• Body mass index (BMI) ≥25.0 kilogram per square meter (kg/m^2) at screening.

• Diagnosis of type 2 diabetes (T2D) ≥180 days before screening.

• Stable daily and/or weekly dose(s) ≥90 days before screening of any of thefollowing anti-diabetic drug(s) or combination regimen(s) at effective ormaximum tolerated dose, as judged by the investigator:

• Treatment with 1-3 marketed oral anti-diabetic drugs (OADs) (metformin, α-glucosidase inhibitors (AGI), glinides, sodium-glucose co-transporter 2inhibitors (SGLT2i), thiazolidinediones, or sulphonylureas (SU) as a singleagent or in combination) according to local guidelines.

• Treatment with basal insulin (including neutral protamine Hagedorn (NPH)insulin) according to local guidelines.

• HbA1c ≤10.5 % (91 millimole per mole [mmol/mol]) and ≥6.5 % (48 mmol/mol), asdetermined by central laboratory at screening.

• Diagnosis of painful diabetic peripheral neuropathy (pDPN) based on the followingcriteria:

• Participant with self-reported pain consistent with pDPN for a minimum of 3months before screening, as judged by the investigator. AND

• Michigan Neuropathy Screening Instrument (MNSI) q≥4 or e≥2.5 at screening. AND

• Douleur Neuropathique en 4 Questions (DN4) (Question 1 and 2) ≥4 at screening.

• The weekly average in Pain Intensity-Numerical Rating Scale (PI-NRS) score must meetthe following criteria in both weeks during the screening period (day -15 to -8 andday -7 to -1):

• Completion of daily PI-NRS reporting in the eDiary for a minimum of 4 out of 7days each week. AND

• The weekly average PI-NRS score must be ≥4.0. AND

• The standard deviation (SD) of the weekly average PI-NRS score must be ≤2.0.

• Stable pharmacological and non-pharmacological treatment of pain for a minimum of 3months before screening, in the opinion of the investigator. The treatment regimenshould adhere to local guidelines (if available).

Key Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is ofchildbearing potential and not using a highly effective contraceptive method.

• Use of any glucagon-like peptide-1 receptor agonist (GLP-1 RA), including medicationwith GLP-1 RA activity, or amylin analogue within 60 days before screening.

• Significant use of opioids, cannabinoids or benzodiazepines within 30 days beforescreening, in the opinion of the investigator.

• Anticipated initiation or clinically relevant change in concomitant medications (formore than 14 consecutive days during the study) known to affect weight or glucosemetabolism (e.g., orlistat, thyroid hormones or oral corticosteroids).

• Planned initiation or change in anti-depressant, anti-psychotic or anti-epilepticmedication. If participants are already taking such medication, they should havestable and optimised treatment for at least 8 weeks before screening.

• Presence or history of epilepsy and fibromyalgia.

• Presence of non-diabetic neuropathies, in the opinion of the investigator.

• Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verifiedby a fundus examination and OCT assessment performed within 90 days before screeningor in the period between screening and randomisation. Pharmacological pupil-dilationis a requirement unless using a digital fundus photography camera specified fornon-dilated examination.

• Any other painful medical condition(s) where the pain is significantly more severethan the diabetic peripheral neuropathy pain, as judged by the investigator (participants will not be excluded if the pain is transient in nature).

• History of suicidal attempt within 5 years before screening

• Suicidal behaviour within 1 month before screening.

• Renal impairment with estimated Glomerular Filtration Rate (eGFR) <30 ml/min/1.73 m2as determined by central laboratory at screening.

• Exposure to an investigational medicinal product within 90 days or 5 half-lives ofthe investigational medicinal product (if known), whichever is longer, beforescreening.