Evaluation of Cagrilintide and Semaglutide Combination for Weight Reduction in Patients with Overweight, Obesity, and Type 2 Diabetes

The primary objective is to confirm the superiority of CagriSema versus placebo on body weight reduction as an adjunct to reduced‑calorie diet and increased physical activity in participants with overweight or obesity and type 2 diabetes. Secondary objectives are to:

• demonstrate superiority of CagriSema versus placebo for ≥20% weight loss, weight loss at week 20, waist circumference, glycated hemoglobin, systolic blood pressure and physical functioning;
• compare the safety and tolerability of CagriSema with placebo.

The trial enrolled 784 participants, including both male and female adults aged 18 years and older. Eligible individuals had a BMI of ≥27 kg/m² and a confirmed diagnosis of type 2 diabetes for at least 180 days before screening. All subjects were receiving either lifestyle modification alone or a stable regimen of one to three oral antidiabetic drugs for a minimum of 90 days, with HbA1c values between 7 % and 10 % as measured by a central laboratory. Participants were required to follow a reduced‑calorie diet and increase physical activity as part of the study protocol. Selection was based on these criteria to ensure inclusion of patients with overweight or obesity and the specified glycemic control range.

The study is a phase III, placebo‑controlled trial evaluating the efficacy and safety of cagrilintide semaglutide administered subcutaneously once weekly in participants with overweight or obesity and type 2 diabetes. Eligible participants are adults (≥18 years) with a BMI ≥ 27 kg/m², a diagnosis of diabetes for at least 180 days, stable oral antidiabetic therapy for ≥90 days, and a central‑lab HbA1c of 7 %–10 % at screening. After an initial screening visit to confirm eligibility, participants are randomized to receive either the investigational combination or placebo alongside a reduced‑calorie diet and increased physical activity. Follow‑up visits are scheduled throughout the study to monitor body weight, waist circumference, HbA1c, blood pressure, quality‑of‑life measures, and adverse events, with the primary endpoints being relative change in body weight and the proportion achieving ≥5 % weight loss. The trial concludes with an end‑of‑study visit that finalizes efficacy and safety assessments. Recruitment commenced on 1 February 2023 and the study is planned to end on 29 January 2025, encompassing the full period of participant involvement from screening to final assessment.

The investigational product is a fixed‑dose combination of cagrilintide and semaglutide supplied as a solution for injection. The preparation is administered by the subcutaneous route at a dose of 0 mg for each active substance, provided in a single injection once weekly.

The comparator arm consists of a matching placebo formulation designated as “Placebo + Placebo.” This product contains no active pharmaceutical ingredients, is presented as a non‑active solution for injection, and is administered subcutaneously on the same weekly schedule as the active combination.

Dosing occurs once per week throughout the treatment period. Study protocol mandates that each dose be recorded in the participant’s dosing log, and compliance is verified by review of returned medication containers and review of the dosing records at each study visit. Compliance monitoring procedures are applied uniformly to both the active and placebo arms.

Primary efficacy will be evaluated by the relative change in body weight from baseline and by the proportion of participants achieving a ≥ 5 % reduction in body weight. Body weight will be measured with calibrated scales at baseline and at each scheduled efficacy visit, and the changes will be calculated using pre‑specified statistical methods to assess superiority of the investigational regimen versus placebo.

Secondary efficacy assessments will include achievement of ≥ 20 % weight reduction, change in waist circumference, change in Glycated Haemoglobin (HbA1c), change in systolic blood pressure, and changes in patient‑reported outcome instruments (Impact of Weight on Quality Of Life‑Lite Clinical Trials Version Physical Function score and SF‑36v2 Acute Physical Functioning score). Safety‑related efficacy metrics such as the number of treatment‑emergent adverse events, treatment‑emergent serious adverse events, and hypoglycaemic episodes (levels 2 and 3) will also be recorded. These parameters will be captured using standard laboratory assays for HbA1c, automated sphygmomanometers for blood pressure, tape measures for waist circumference, and validated questionnaires for quality‑of‑life and physical functioning, with data collected at baseline and at each predefined study visit throughout the treatment period.