A Phase 3, randomised, double-blind, parallel-group, 76-week, efficacy and safety study of BI 456906 administered subcutaneously compared with placebo in participants with overweight or obesity and type 2 diabetes mellitus

The primary objective of this Phase 3, randomized, double-blind, parallel-group study is to evaluate the **efficacy**, safety, and **tolerability** of survodutide, administered subcutaneously, as an adjunct to a reduced-calorie diet and increased physical activity, compared to placebo in participants with a body mass index (BMI) ≥27 kg/m² and type 2 diabetes mellitus (T2DM). The primary aim is to demonstrate the superiority of both low and high doses of survodutide over placebo. This is clinically relevant as it addresses the management of overweight or obesity in individuals with T2DM, a population at increased risk for cardiovascular and metabolic complications.

Secondary objectives include demonstrating the superiority of survodutide, at both low and high doses, against placebo concerning the secondary endpoints specified in the clinical trial protocol. These secondary endpoints are crucial for understanding the broader impact of survodutide on health outcomes beyond weight loss, potentially influencing future therapeutic strategies for managing obesity and T2DM.

The clinical trial involves a total of **508 participants** diagnosed with **Type 2 Diabetes Mellitus** and **obesity**. The study population includes both male and female subjects aged 18 years and older, with a **Body Mass Index (BMI)** of 27 kg/m² or higher. Participants were selected based on their diagnosis of Type 2 Diabetes Mellitus, with a glycosylated hemoglobin A1c (HbA1c) level of at least 6.5% but less than 10%, and a history of at least one self-reported unsuccessful dietary effort to lose body weight. The trial population is required to follow a reduced-calorie diet and increase physical activity as part of the study protocol. Participants may be currently treated for Type 2 Diabetes Mellitus with diet and exercise alone or with stable treatment using specific anti-hyperglycemia medications. The trial includes a vulnerable population, ensuring a comprehensive assessment of the investigational product's efficacy, safety, and tolerability.

The clinical trial is designed as a **randomized, double-blind, controlled** study to evaluate the efficacy and safety of **survodutide** administered subcutaneously in participants with **type 2 diabetes mellitus** and **obesity**. The trial will span a total duration of 76 weeks, with the primary objective of demonstrating the superiority of survodutide over placebo in achieving weight reduction. Participants will be randomly assigned to receive either the investigational product, BI 456906, or a placebo, both administered as a **solution for injection**. The trial will include a screening visit to assess eligibility based on criteria such as age, body mass index (BMI), and diabetes management. Eligible participants will then proceed to the randomization phase.

Throughout the trial, participants will attend regular follow-up visits to monitor safety, efficacy, and adherence to the treatment protocol. These visits will include assessments of body weight, **glycosylated hemoglobin A1c (HbA1c)** levels, and other relevant health parameters. The primary endpoints include the percentage change in body weight and the achievement of a body weight reduction of at least 5% from baseline to week 76. Secondary endpoints will evaluate further weight reduction milestones and changes in metabolic and behavioral parameters. The end-of-study visit will conclude the trial, where final assessments will be conducted to gather comprehensive data on the long-term effects of the treatment.

Participant involvement is expected to last for the entire 76-week duration unless early termination is warranted. Conditions that may lead to early withdrawal include adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial aims to provide valuable insights into the potential benefits of survodutide as an adjunct to lifestyle modifications in managing weight and glycemic control in individuals with type 2 diabetes and obesity.

The clinical trial involves the administration of **BI 456906**, a **solution for injection** developed by Boehringer Ingelheim International. The active substance, **survodutide**, is a protein of other origin. The pharmaceutical form is a solution for injection, and the medication is administered via **subcutaneous use**. The dosing schedule varies, with a maximum treatment period of up to 60 weeks, depending on the specific protocol for each participant. The dosage is measured in milligrams, although specific daily and total dose amounts are not provided. The trial aims to evaluate the efficacy, safety, and tolerability of survodutide as an adjunct to a reduced-calorie diet and increased physical activity in participants with a BMI ≥27 kg/m² and type 2 diabetes mellitus.

In addition to the experimental treatment, a **placebo** is used as a comparator in the study. The placebo is not specified in terms of pharmaceutical form or active substance, as it serves as a control to assess the effects of the experimental medication. The placebo is administered under the same conditions as the experimental treatment to ensure blinding and maintain the integrity of the trial results.

Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol. The trial is designed to demonstrate the superiority of survodutide at both low and high doses compared to the placebo, with the primary objective being the assessment of its efficacy in reducing weight in participants with overweight or obesity and type 2 diabetes mellitus.

The efficacy of the clinical trial will be assessed through a series of primary and secondary endpoints. The primary endpoints include the percentage change in body weight from baseline to Week 76 and the achievement of a body weight reduction of at least 5% from baseline to Week 76. Secondary endpoints will evaluate further weight reduction milestones, such as achieving a body weight reduction of 10%, 15%, and 20% from baseline to Week 76. Additionally, absolute changes from baseline to Week 76 will be measured in several parameters: body weight (kg), **HbA1c** (%), waist circumference (cm), systolic blood pressure (SBP) (mmHg), and scores from the Eating Behaviour Patient-Reported Outcome (PRO) tool, specifically the "Capacity to Resist" domain score and the total score.

The trial will involve the administration of BI 456906, a solution for injection, compared to a placebo, with the treatment period extending up to 76 weeks. Efficacy assessments will be conducted at specified intervals throughout the trial, with the final evaluation occurring at the end of the treatment period. The data collected will be analyzed to determine the efficacy of BI 456906 in achieving the specified weight reduction and metabolic control goals in participants with overweight or obesity and type 2 diabetes mellitus.