Phase 3 Randomized, Placebo‑Controlled Trial Assessing Efficacy and Safety of MET097, a Long‑Acting GLP‑1 Receptor Agonist, in Overweight/Obese Adults with Type 2 Diabetes

The primary objective is to assess whether once‑weekly administration of MET097 at the CCI mg dose produces a superior percent change from baseline body weight at week 64 compared with placebo in participants with overweight or obesity and type 2 diabetes. Demonstrating a greater reduction in body weight would support the therapeutic potential of this ultra‑long‑acting GLP‑1 receptor agonist for weight management in this population.

Secondary objectives include:

• Evaluation of the superiority of MET097 on HbA1c change from baseline at week 64.
• Assessment of absolute body‑weight reduction at week 64.
• Investigation of the effect on lipids and lipoproteins at week 64.
• Measurement of change in systolic blood pressure from baseline at week 64.
• Comparison of patient‑reported outcomes for physical functioning at week 64.
• Analysis of the percent change in body weight at week 84.
• Evaluation of absolute body‑weight change at week 84.
• Assessment of HbA1c change from baseline at week 84.

The trial enrolled 80 adult participants, both male and female, who were at least 18 years of age and met a body‑mass‑index threshold of ≥27 kg/m², indicating obesity. All subjects had a documented history of type 2 diabetes mellitus for a minimum of six months and demonstrated HbA1c values between 6.5 % and 10.0 % while receiving stable antidiabetic therapy (excluding DPP‑4 inhibitors, GLP‑1 agonists, and insulin) for at least 90 days prior to screening. Enrollment required a signed informed‑consent form and the ability to adhere to trial procedures, including self‑administration of the weekly subcutaneous study drug, regular finger‑stick glucose monitoring, and compliance with prescribed dietary restrictions and an exercise plan. Participants were selected on the basis of these clinical and behavioral criteria to ensure a motivated population capable of following the study protocol throughout the 64‑week period.

The study is a randomized, double-blind, placebo-controlled Phase 3 trial evaluating weekly subcutaneous administration of MET097 (5 mg/mL) versus matching placebo in adults with a BMI ≥ 27 kg/m² and type 2 diabetes. After obtaining written informed consent, participants attend a screening visit to confirm eligibility, record baseline body weight, HbA1c, and safety laboratory values, and undergo randomization. Study drug is administered once weekly for a total duration of 84 weeks, with scheduled follow‑up visits at weeks 4, 12, 24, 36, 48, 64, and 84 to assess body weight, glycaemic control, vital signs, laboratory safety parameters, and patient‑reported outcomes. The primary efficacy assessment is the percent change in body weight from baseline to week 64; secondary assessments include absolute weight change, HbA1c change, lipid parameters, blood pressure, and health‑related quality of life at weeks 64 and 84. Participants are expected to remain in the study for approximately 20 months, encompassing the treatment period and final end‑of‑study visit at week 84. Early termination may occur if a participant experiences a serious adverse event related to the investigational product, requires prohibited medication (e.g., GLP‑1 agonists or insulin), demonstrates non‑compliance with study procedures, or withdraws consent.

The investigational product is MET097, supplied as a 5 mg/mL solution for injection in a sterile vial. The formulation is administered by subcutaneous injection once weekly (QW) throughout the 64‑week treatment period. The dosing schedule follows a titration protocol that escalates to the target weekly dose, after which the assigned dose is maintained until study completion.

The comparator is a matching placebo presented in an identical vial and presentation, containing no active peptide. The placebo is administered by the same subcutaneous route and frequency as the active product to preserve blinding.

All study medications are prepared by qualified personnel in accordance with aseptic technique and are logged in the trial pharmacy. Dosing is recorded in the source documents, and participants receive training on self‑administration. Compliance is monitored by counting returned devices, electronic injection logs, and periodic serum drug‑level assessments where applicable.

The efficacy assessment will focus on changes from baseline in several predefined parameters. The primary efficacy parameter is percent change from baseline in body weight at Week 64. Secondary parameters include absolute body‑weight change (kg) at Weeks 64 and 84, change in HbA1c (%) at the same time points, reductions in fasting triglycerides (mg/dL) and non‑high‑density lipoprotein cholesterol (non‑HDL‑C, mg/dL) at Week 64, change in systolic blood pressure (mmHg) at Week 64, and the Short Form‑36 (SF‑36) physical function domain score at Week 64. Additional efficacy evaluations consist of percent body‑weight reduction at Week 84 and HbA1c change at Week 84.

All efficacy parameters will be measured at baseline and at the specified study visits (Weeks 64 and 84). Body‑weight and blood‑pressure measurements will be obtained using calibrated scales and sphygmomanometers, respectively. Laboratory assessments for HbA1c, fasting triglycerides, and non‑HDL‑C will be performed with standard, validated assays. The SF‑36 questionnaire will be administered to capture health‑related quality‑of‑life outcomes. Data will be analyzed by comparing the MET097 group to the placebo group using appropriate statistical methods for continuous and categorical outcomes, with significance testing conducted at the prespecified time points.