Efficacy and Safety of Cagrilintide and Semaglutide in Participants with Type 2 Diabetes Inadequately Controlled on Metformin with or without SGLT2 Inhibitors

The primary objective is to confirm the superiority of co-administered cagrilintide and semaglutide regarding the change in HbA1c in participants with type 2 diabetes experiencing inadequate glycaemic control while on a stable dose of metformin with or without an SGLT2 inhibitor. 5 The secondary objectives include:

• Evaluation of changes in body weight, including the achievement of weight reduction thresholds of ≥5%, ≥10%, ≥15%, and ≥20%.
• Assessment of glycaemic control parameters, specifically time in range (TIR) and time in tight range (TITR).
• Measurement of metabolic and cardiovascular markers, such as systolic blood pressure, diastolic blood pressure, triglycerides, non-HDL cholesterol, and lipids.
• Analysis of inflammatory and endocrine biomarkers, including hsCRP, leptin, and soluble leptin receptor.
• Evaluation of renal biomarkers and inflammation.
• Assessment of waist circumference and overall clinical outcome assessments.
• Comparison of safety and tolerability across treatment groups.

This study involves 1,505 participants diagnosed with type 2 diabetes. The study population consists of both male and female individuals, including vulnerable groups, with an age range categorized under codes 3 and 4. Eligible participants must have been diagnosed with the condition at least 180 days prior to screening and must possess a body mass index of at least 25 kg/m2. A requirement for inclusion is the maintenance of a stable daily dose of metformin, with or without SGLT2 inhibitors, for at least 90 days. Additionally, participants must demonstrate an HbA1c level between 7.0% and 10.5% as determined by a central laboratory.

This study is a phase 3a confirmatory clinical trial designed to evaluate the efficacy and safety of cagrilintide semaglutide in participants with type 2 diabetes. The research utilizes a comparative design to investigate the effects of various doses of the test product against semaglutide, cagrilintide, or a placebo. Participants are required to be on a stable dose of metformin, with or without an SGLT2 inhibitor, for at least 90 days prior to screening. The primary endpoint is the change in HbA1c from baseline to the end of the 68-week treatment period. Additional secondary endpoints include changes in body weight, fasting plasma glucose, and various metabolic and glycemic parameters measured via continuous glucose monitoring. The study protocol involves a screening visit to assess eligibility, followed by a 68-week treatment phase, and concludes with an end-of-study assessment at week 75 to monitor treatment-emergent adverse events. The total duration of participant involvement is approximately 75 weeks. Early termination from the study may occur based on investigator discretion or specific safety criteria.

The experimental treatment consists of cagrilintide and semaglutide administered as a fixed-dose combination in a solution for injection. This test substance is provided via subcutaneous administration once weekly.

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

Background therapies consist of metformin and dapagliflozin, which are administered in oral form. These medications are used for participants with type 2 diabetes.

The primary efficacy endpoint is the change in HbA1c from baseline at week 0 to the end of treatment at week 68. Secondary efficacy assessments include the evaluation of relative change in body weight and the achievement of specific weight reduction thresholds, including ≥5%, ≥10%, ≥15%, and ≥20% from baseline.

Additional efficacy parameters include:

• Continuous Glucose Monitoring (CGM) metrics, specifically changes in time in range (TIR), time in tight target range (TITR), time above range, and glycaemic variability.
• Changes in fasting plasma glucose (FPG) and achievement of HbA1c target values of ≤6.5% or <7.0%.
• Changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), and waist circumference.
• Alterations in lipid profiles, including ratios to baseline for triglycerides, non-HDL cholesterol, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, and free fatty acids.
• Changes in high sensitivity C-reactive protein (hsCRP).
• Patient-reported outcomes using the SF-36v2 score, Diabetes Treatment Satisfaction Questionnaire (DTSQ), and Treatment Related Impact Measure for Diabetes (TRIM-D).