Efficacy and safety of subcutaneous once-weekly zenagamtide in participants with overweight or obesity and type 2 diabetes

The primary objective of this study is to evaluate the efficacy of NNC0487-0111 compared to placebo by assessing the change in body weight in participants with overweight or obesity and type 2 diabetes. The secondary objectives aim to confirm the superiority of various doses of NNC0487-0111 versus placebo regarding the following clinical outcomes:

• Waist circumference
• Haemoglobin A1c
• Systolic blood pressure
• Physical functioning

This clinical trial involves a total of 365 participants. The study population consists of male and female individuals diagnosed with type 2 diabetes and characterized by overweight or obesity. Eligible participants are aged 18 years or older at the time of informed consent. Inclusion requirements include a body mass index within a specified range and a diagnosis of diabetes mellitus at least 180 days prior to screening. Participants must demonstrate a haemoglobin A1c level between 7% and 10%. The population includes individuals receiving a lifestyle intervention and/or stable treatment with zero to three marketed oral antidiabetic drugs, such as metformin, α-glucosidase inhibitors, glinides, sodium-glucose cotransporter 2 inhibitors, thiazolidinediones, or sulfonylureas.

This Phase III clinical trial is designed to evaluate the efficacy and safety of zenagamtide administered via subcutaneous injection once weekly. The study focuses on participants diagnosed with type 2 diabetes and obesity. The primary objective is to confirm the superiority of various doses of zenagamtide compared to a placebo regarding the relative change in body weight. Secondary endpoints include assessments of haemoglobin A1c, waist circumference, blood pressure, lipid profiles, and various quality of life measures. The research methodology involves a controlled comparison to measure clinical outcomes and the incidence of adverse events. The total duration of the study is estimated to span from April 2026 to July 2028.

The experimental treatment consists of zenagamtide, administered as a solution for injection in pre-filled pen. This medication is provided in multiple formulations, identified as NNC0487-0111 B 10141, NNC0487-0111 B 10142, NNC0487-0111 B 10143, NNC0487-0111 B 10144, NNC0487-0111 B 10145, and NNC0487-0111 B 10146. The subcutaneous administration occurs on a once-weekly basis in participants with overweight, obesity, or type 2 diabetes.

The control group receives a placebo as a comparator treatment.

The primary efficacy endpoint is the relative change in body weight in participants with overweight or obesity and type 2 diabetes. Secondary efficacy parameters include the change in body mass index (BMI), change in body weight, and change in waist circumference.

Glycemic control will be assessed through the change in haemoglobin A1c (HbA1c), change in fasting plasma glucose (FPG), change in fasting insulin, and the achievement of specific HbA1c thresholds. Cardiovascular and metabolic parameters include the change in systolic blood pressure (SBP), change in diastolic blood pressure, change in lipids (encompassing total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, and triglycerides), change in high-sensitivity C-reactive protein (hsCRP), and change in urinary albumin-to-creatinine ratio (UACR).

Patient-reported outcomes and quality of life assessments involve the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT), specifically evaluating the physical function score and the physical psychosocial total score. Additionally, the SF-36v2® Health Survey Acute (SF-36v2 Acute) physical functioning score will be utilized for assessment.