Efficacy and Safety of Cagrilintide and Semaglutide in Patients with Type 2 Diabetes, Chronic Kidney Disease, and Overweight or Obesity

The primary objective is to investigate the efficacy of co-administered cagrilintide and semaglutide compared to its individual components and placebo in improving surrogate markers of chronic kidney disease progression in individuals with type 2 diabetes and overweight or obesity.

Secondary objectives include the comparison of the co-administered therapy against monocomponents and placebo regarding the following parameters:

• Weight-related parameters
• Glycaemic control
• Blood pressure
• Safety and tolerability

This clinical trial involves a total of 310 participants, comprising both male and female individuals. The study population consists of patients diagnosed with type 2 diabetes and chronic kidney disease. Eligible subjects must be aged 18 years or older and exhibit overweight or obesity, defined by a body mass index of at least 27.0 kg/m2. Inclusion requires a glycated hemoglobin level of 10.5% or less and a specific range of estimated glomerular filtration rate between 15 and 90 mL/min/1.73 m2. Additionally, participants must present with albuminuria characterized by a urinary albumin-to-creatinine ratio between 100 and 5000 mg/g. The population must also be receiving a stable dose of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker.

This phase 4 clinical trial is designed to investigate the efficacy and safety of cagrilintide semaglutide compared to semaglutide, cagrilintide, and placebo in individuals with type 2 diabetes and chronic kidney disease presenting with overweight or obesity. The study methodology involves the administration of subcutaneous solution for injection. The primary endpoint is the change in the urinary albumin-to-creatinine ratio (UACR) from baseline to the end of treatment. Secondary endpoints include changes in the estimated glomerular filtration rate (eGFR), glycated haemoglobin (HbA1c), body weight, waist circumference, and blood pressure, as well as the frequency of adverse events and hypoglycaemia. Participants may receive background therapies such as finerenone, dapagliflozin, or enalapril. The recruitment period for this study is estimated to occur between April 2024 and November 2025.

The experimental treatment consists of cagrilintide and semaglutide administered as a fixed-dose combination. This medication is provided as a solution for injection for subcutaneous administration.

Comparator treatments include semaglutide and cagrilintide, both administered as a solution for injection via a subcutaneous route. A placebo is also utilized in the study design.

Background therapies may include finerenone, enalapril maleate, or dapagliflozin propanediol, which are administered through an oral route.

The primary efficacy endpoint is the change in UACR from baseline to the end of treatment. Secondary endpoints include the change in eGFR calculated using both creatinine and cystatin C-based CKD-EPI 2021 and creatinine-based CKD-EPI 2021 from baseline to end of treatment. Other secondary parameters involve the relative change in body weight, the achievement of weight reduction of at least 5% or 10%, and the change in waist circumference from baseline to end of treatment. Metabolic and hemodynamic assessments consist of changes in glycated haemoglobin (HbA1c), systolic blood pressure, and diastolic blood pressure from baseline to end of treatment. Safety and tolerability are evaluated through the number of treatment emergent adverse events (TEAEs), treatment emergent serious adverse events (SAEs), and the frequency of hypoglycaemic episodes, specifically level 2 episodes confirmed by a BG meter and level 3 episodes involving cognitive impairment.