This Phase II study is a randomized, parallel group, double blinded, placebo-controlled, multicenter to evaluate the efficacy, safety, and tolerability of AZD6234 in adults with overweight or obesity and type 2 diabetes on stable GLP-1 RA therapy.

This is a Phase II, randomised, parallel-group, double-blind, placebo-controlled, multi-centre study to assess the efficacy, safety, and tolerability of AZD6234 compared with placebo, given once weekly as a subcutaneous (SC) injection, in adults living with overweight or obesity and type 2 diabetes who are on a stable dose of GLP-1 RA. The study is being conducted across sites in the USA to evaluate the efficacy, safety, and tolerability of AZD6234 in adults with overweight or obesity and type 2 diabetes on stable GLP-1 RA therapy. A total of 64 Participants, aged 18-75 with a BMI ≥ 27 kg/m², will be randomized to receive weekly subcutaneous injections of either AZD6234 or a placebo, alongside their current GLP-1 RA medication. The study involves a screening period and a treatment and follow-up period.

Inclusion Criteria:

1. Be 18 to 75 years old at the time of signing the informed consent.
2. Diagnosed with type 2 diabetes ≥ 180 days before screening.
3. HbA1c value at screening of ≥ 6.0% (42 mmol/mol) and ≤ 10% (86 mmol/mol).
4. On a stable maintenance dose of an injectable GLP-1 RA.
5. At Screening, have a BMI ≥ 27 kg/m2

Exclusion Criteria:

1. Has received treatment with prescription or non-prescription medication for weight loss within the last 3 months prior to screening (other than a GLP-1 RA).
2. Self-reported weight change of > 5 % in the 3 months prior to screening.
3. Diabetes mellitus that is not clearly type 2 diabetes.
4. Use of insulin therapy for T2DM
5. Previous or planned (within study period) bariatric surgery or fitting of a weight loss device (eg, gastric balloon or duodenal barrier)
6. Significant hepatobiliary disease (except for non-alcoholic steatohepatitis or nonalcoholic fatty liver disease without portal hypertension or cirrhosis)

8. Impaired renal function defined as eGFR ≤ 45 mL/minute/1.73m2 at screening

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org.

Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

This study will be conducted as double-blind through its duration, with participants, investigators, and site staff remaining blinded to treatment allocation. At the time of the interim analysis, Sponsor and designated CRO staff will be unblinded to treatment allocations solely for statistical analysis or operational management. Investigators, site staff, and participants will remain blinded for the entire study duration.