Phase III Randomized, Double‑Blind, Placebo‑Controlled Study of Elecoglipron in Adults with Obesity or Overweight, With or Without Type 2 Diabetes Mellitus

The primary objective is to determine whether elecoglipron is superior to placebo for percent body weight loss in adults with obesity or overweight, with or without type 2 diabetes mellitus, reflecting a clinically meaningful reduction in adiposity that can improve metabolic risk.

Secondary objectives include:

• Assessment of absolute body weight loss compared with placebo.
• Proportion of participants achieving total body weight loss of ≥5%, ≥10% and ≥15% from baseline.
• Percent body weight loss in participants with baseline BMI ≥27 kg/m².
• Reduction in waist circumference.
• Improvement in glycemic control.
• Achievement of normoglycemia in participants with baseline HbA1c ≥5.7%.
• Achievement of glycemic control in participants with baseline HbA1c ≥7.0% (Study 2).
• Reduction in systolic blood pressure.

The trial enrolled 3,490 adult participants aged 18 years and older, comprising both female and male individuals, including vulnerable subjects. All participants were classified as having obesity or overweight and presented with at least one weight‑related comorbidity; some also had type 2 diabetes mellitus. Enrollment required a body‑mass index (BMI) of ≥30 kg/m², or a BMI of 27–<30 kg/m² accompanied by hypertension, prediabetes, dyslipidemia, cardiovascular disease, or obstructive sleep apnea in the first study, and a BMI of ≥27 kg/m² with a confirmed diagnosis of type 2 diabetes mellitus or HbA1c ≥6.5 % in the second study. Candidates must have demonstrated a stable body weight (±5 % change) for at least 90 days prior to screening and reported at least one prior unsuccessful dietary effort to lose weight. The population was selected from patients meeting these criteria without further restriction on other lifestyle factors.

The trial is a Phase III, multicenter, master protocol that employs a randomized, double‑blind, placebo‑controlled design to evaluate the efficacy and safety of the oral film‑coated tablet Elecoglipron in adults with obesity or overweight, with or without type 2 diabetes mellitus. Eligible participants (≥18 years, BMI criteria as specified, stable body weight for ≥90 days, and a history of at least one unsuccessful dietary effort) undergo a screening visit to confirm eligibility, obtain baseline measurements, and collect laboratory data; qualified individuals are then randomized in a 1:1 ratio to receive either Elecoglipron or matching placebo. After randomization, participants attend scheduled follow‑up visits at regular intervals through Week 72, during which study drug compliance, adverse events, body weight, waist circumference, hemoglobin A1c, and blood pressure are assessed. The primary efficacy endpoint—percent change in body weight from baseline to Week 72—is evaluated at the end‑of‑study visit at Week 72, together with a series of secondary endpoints. Participant involvement therefore extends from the initial screening encounter through the final Week 72 assessment, encompassing approximately 72 weeks of treatment and observation.

The investigational product, Elecoglipron, is supplied as a film‑coated tablet for oral administration. Each tablet contains 0 mg of the active ingredient (dose unit: milligram). The tablets are to be taken once daily by mouth, with dosing schedule and possible titration defined in the study protocol. Compliance with the dosing regimen is monitored through tablet count at each study visit and electronic dosing diaries.

The control arm receives a matching placebo formulated to be indistinguishable from the active tablet. The placebo is administered orally once daily under the same conditions as the investigational product, ensuring blinding of participants and investigators. Compliance with placebo administration is similarly assessed by tablet count and dosing diaries.

Efficacy will be evaluated primarily by the percent change from baseline to Week 72 in body weight. Body weight will be measured at study entry and at Week 72, and the percentage difference between these time points will be compared between the Elecoglipron and placebo groups.

Secondary efficacy assessments include the absolute change in body weight at Week 72, the proportion of participants achieving ≥ 5 %, ≥ 10 % and ≥ 15 % body weight loss, the percent change in body weight among subjects with baseline BMI ≥ 27 kg/m², the absolute change in waist circumference, the change in systolic blood pressure, and glycemic outcomes. Glycemic outcomes comprise the change in hemoglobin A1c (HbA1c) from baseline to Week 72, the proportion attaining normoglycemia (HbA1c < 5.7 %), and, in Study 2, the proportions achieving HbA1c < 7.0 % and ≤ 6.5 % among participants with elevated baseline values. All secondary parameters will be measured at baseline and again at Week 72, with comparative statistical analyses performed to determine differences between treatment arms.