Phase III Randomized Open‑Label Trial Evaluating Elecoglipron Versus Oral Semaglutide for Glycemic Control in Adults with Type 2 Diabetes Mellitus

The primary objective is to assess the efficacy of elecoglipron versus oral semaglutide in achieving glycemic control in adults with type 2 diabetes mellitus, providing data on comparative HbA1c reduction to inform therapeutic choices. Secondary objectives encompass evaluation of additional efficacy and safety outcomes, including:

• Magnitude of body weight reduction with elecoglipron compared with oral semaglutide.
• Combined effect on body weight reduction and glycemic control.
• Isolated assessment of glycemic control.
• Safety and tolerability of the investigational agent.
• Pharmacokinetic profile of elecoglipron.

The trial enrolled 865 participants diagnosed with type 2 diabetes mellitus, comprising both male and female adults, including individuals classified as vulnerable. Eligibility required a diagnosis of diabetes for at least 90 days, inadequate glycemic control despite lifestyle management alone or the use of up to two oral glucose‑lowering agents, an HbA1c between 7 % and 10.5 % (53–91.3 mmol/mol), and a body‑mass index of ≥ 23 kg/m² with stable weight for the preceding 90 days. Participants also needed to exhibit an elevated cardiovascular risk, defined by a history of coronary heart disease, peripheral arterial disease, ischemic cerebrovascular disease, heart failure (NYHA class II–III), or the presence of two or more cardiovascular risk factors. The population reflected a broad range of adult patients with diabetes who were managed under real‑world conditions, incorporating typical lifestyle considerations such as diet and physical activity alongside medication regimens.

The study is a Phase III, randomized, open‑label, parallel‑group trial evaluating the efficacy, safety, and tolerability of elecoglipron compared with oral semaglutide in adults with type 2 diabetes mellitus. After an eligibility screening visit, participants who meet inclusion criteria are randomized to receive either elecoglipron or one of the semaglutide tablets (Rybelsus 1.5 mg, 4 mg, or 9 mg) and begin treatment at baseline (week 0). Follow‑up visits are scheduled regularly throughout a 52‑week treatment period to monitor glycemic control, body weight, adverse events, and protocol compliance, culminating in an end‑of‑study visit at week 52. Participant involvement therefore extends from the screening encounter through the final assessment at week 52, encompassing approximately one year of study participation. The primary efficacy endpoint is the change from baseline to week 52 in HbA1c, with secondary endpoints including weight change and achievement of predefined HbA1c and weight‑loss targets.

The investigational product, elecoglipron, is provided as a film‑coated tablet for oral administration. The tablet is supplied in a strength listed as 0 mg in the source data; therefore, the specific dose and dosing frequency are defined by the study protocol. Participants receive the tablet according to the scheduled dosing regimen, and adherence is monitored through pill counts, electronic medication diaries, and periodic compliance assessments conducted by study staff.

The comparator arm utilizes oral semaglutide marketed as Rybelsus tablets in three dosage strengths: 1.5 mg, 4 mg, and 9 mg. Each strength is supplied as a tablet intended for oral use and is administered once daily. The appropriate dose for each participant is selected according to the protocol‑specified titration schedule. Compliance with the comparator therapy is similarly monitored by pill counts, patient diaries, and regular review of dosing records.

Efficacy will be assessed by comparing the change from baseline to Week 52 in HbA1c (%) between the test and comparator arms. Baseline values will be recorded prior to randomization, and the same laboratory measurement will be repeated at Week 52 to determine the primary endpoint.

Secondary efficacy assessments will include the percent change and absolute change in body weight (kg) from baseline to Week 52, the proportion of participants achieving ≥ 5% weight loss together with HbA1c < 7% (53 mmol/mol) at Week 52, and the proportions achieving HbA1c ≤ 6.5% (48 mmol/mol) or HbA1c < 7% at Week 52. All secondary parameters will be evaluated using the values obtained at baseline and at the Week 52 visit.