Phase III Randomized, Double‑Blind Study of Elecoglipron versus Placebo for Glycemic Control in Adults with Type 2 Diabetes Mellitus on Basal Insulin

The primary objective is to assess the efficacy of elecoglipron (dose A and dose B) versus placebo in achieving improved type 2 diabetes mellitus glycemic control when added to background insulin therapy, reflecting the therapeutic goal of lowering blood glucose in this population. Secondary objectives include evaluation of elecoglipron versus placebo for additional clinical outcomes:

• Glycemic control, body weight reduction, and systolic blood pressure reduction.
• Glycemic control, diastolic blood pressure reduction, and insulin dose reduction.

The trial enrolled 400 adult participants of both sexes diagnosed with type 2 diabetes mellitus. Eligible individuals were required to have a documented diagnosis for at least 90 days, be on a stable regimen of insulin with up to two oral glucose‑lowering agents, and present an HbA1c between 7% and 10.5%. Inclusion also mandated a BMI of ≥23 kg/m² and stable body weight for 90 days prior to screening. Participants were selected from the patient population meeting these criteria, with no additional lifestyle restrictions reported. The cohort comprised both male and female subjects, and vulnerable status was not excluded. General health status was limited to individuals with stable diabetes management, without mention of other comorbidities.

The study is a Phase III, randomized, double‑blind, parallel‑group, placebo‑controlled trial evaluating the efficacy, safety, and tolerability of oral elecoglipron film‑coated tablets in adults with type 2 diabetes mellitus receiving background insulin therapy. After an initial screening visit to confirm eligibility criteria (diagnosis ≥ 90 days, stable insulin regimen, HbA1c 7 %–10.5 %, BMI ≥ 23 kg/m², stable body weight), eligible participants are randomized in a 1:1:1 ratio to one of two elecoglipron dose levels or matching placebo. The treatment period lasts 40 weeks, with study visits scheduled at baseline (Day 0), Week 4, Week 12, Week 24, and Week 40, the latter serving as the end‑of‑study assessment for the primary endpoint (change from baseline in HbA1c%). Secondary assessments include achievement of HbA1c < 7 % or ≤ 6.5 % at Week 40, percent and absolute changes in body weight, and change in systolic blood pressure. Participants remain in the trial for approximately 44 weeks, including the screening phase. Early termination may occur if a participant experiences a serious adverse event, requires rescue medication, demonstrates non‑compliance with the protocol, or withdraws consent.

The investigational product is Elecoglipron, supplied as a film‑coated tablet intended for oral administration. Each tablet contains 0 mg of the active substance elecoglipron. The tablets are to be taken according to the study dosing schedule, which specifies the frequency and duration for each dose level (dose A and dose B) as outlined in the protocol.

The comparator is a matching placebo (AZD5004) formulated to be indistinguishable from the active tablets in appearance. The placebo contains no active pharmaceutical ingredient and is administered by the same oral route and schedule as the investigational product.

Efficacy will be evaluated by comparing changes from baseline to Week 40 in several predefined parameters. The primary efficacy parameter is the change in HbA1c (%) from baseline to Week 40. Secondary efficacy parameters include the proportion of participants achieving an HbA1c level < 7 % (53 mmol/mol) at Week 40, the proportion achieving an HbA1c level ≤ 6.5 % (48 mmol/mol) at Week 40, the percent change in body weight from baseline to Week 40, the absolute change in body weight (kg) from baseline to Week 40, and the change in systolic blood pressure (SBP) from baseline to Week 40.

HbA1c will be measured using a validated high‑performance liquid chromatography assay performed on blood samples collected at baseline and at Week 40. Body weight will be assessed with a calibrated digital scale, and SBP will be measured with an automated sphygmomanometer, both according to standard operating procedures at the same time points. Efficacy analyses will calculate the difference between baseline and Week 40 values for each parameter and will determine the proportion of participants meeting the predefined HbA1c thresholds at Week 40.