Phase III Randomized Double‑Blind Study of Elecoglipron Plus Dapagliflozin Versus Elecoglipron or Dapagliflozin Monotherapy in Adults with Type 2 Diabetes Mellitus

The primary objective is to assess the efficacy of elecoglipron (dose B) combined with dapagliflozin compared with dapagliflozin monotherapy in achieving glycemic control in adults with type 2 diabetes mellitus.

Secondary objectives include:

• Evaluation of elecoglipron (dose A) plus dapagliflozin versus dapagliflozin alone for glycemic control.
• Assessment of elecoglipron (doses A and B) combined with dapagliflozin versus dapagliflozin alone for glycemic control and body‑weight reduction.
• Comparison of elecoglipron (doses A and B) plus dapagliflozin with the corresponding elecoglipron monotherapy for glycemic control, body‑weight reduction, and blood‑pressure reduction.
• Comparison of elecoglipron (doses A and B) monotherapy with dapagliflozin monotherapy for glycemic control, body‑weight reduction, and blood‑pressure reduction.
• Evaluation of the combination of elecoglipron (doses A and B) and dapagliflozin versus dapagliflozin alone for glycemic control, body‑weight reduction, blood‑pressure reduction, and the need for rescue medication.
• Evaluation of the combination of elecoglipron (doses A and B) and dapagliflozin versus the corresponding elecoglipron monotherapy for glycemic control, body‑weight reduction, blood‑pressure reduction, and rescue medication use.
• Evaluation of elecoglipron (doses A and B) monotherapy versus dapagliflozin monotherapy for glycemic control, body‑weight reduction, blood‑pressure reduction, and rescue medication use.

The trial enrolled 1,640 individuals diagnosed with type 2 diabetes mellitus who met predefined eligibility parameters. Both male and female adults were included, representing middle‑aged to older age categories (codes 3 and 4) and encompassing vulnerable participants. Eligibility required a documented diagnosis of the disease for at least 90 days, inadequate glycemic control with lifestyle measures alone or metformin, HbA1c between 7 % and 10.5 %, and a body‑mass index of at least 23 kg/m² with stable body weight for the preceding 90 days. Participants were generally in otherwise stable health, without concurrent glucose‑lowering agents other than metformin where applicable, and were expected to continue their usual diet and physical activity regimens throughout the study. Selection was based on these inclusion criteria, with exclusion of individuals not meeting the specified metabolic or weight stability thresholds.

The study is a Phase III, randomized, double-blind, parallel-group, placebo‑controlled trial evaluating the efficacy, safety, and tolerability of elecoglipron in combination with dapagliflozin versus each agent alone in adults with type 2 diabetes mellitus. After an initial screening visit to confirm eligibility (diagnosis ≥90 days, HbA1c 7–10.5 %, BMI ≥23 kg/m², stable weight), participants are randomized to one of four double‑dummy arms (elecoglipron + dapagliflozin, elecoglipron + placebo, dapagliflozin + placebo, double placebo) and receive study medication orally for 40 weeks. Study visits occur at baseline (Week 0), Weeks 4, 12, 24, and 40 for efficacy assessments (HbA1c, fasting plasma glucose, body weight, blood pressure) and safety monitoring, with an end‑of‑study visit at Week 40 for final evaluations. Total participant involvement spans approximately 42 weeks including screening and follow‑up. Early termination may occur if a participant experiences a serious adverse event, requires rescue medication, demonstrates protocol non‑compliance, or withdraws consent.

The investigational product Elecoglipron is supplied as a film‑coated tablet for oral use. Each tablet contains 00 mg of the active substance elecoglipron. The tablet is administered once daily, with dosing recorded in the study drug log and taken at approximately the same time each day throughout the treatment period.

Dapagliflozin, marketed as Forxiga 10 mg film‑coated tablets, is also administered orally. Each tablet provides 10 mg of dapagliflozin and is taken once daily under the same conditions as the investigational product.

The placebo matching Elecoglipron is a film‑coated tablet identical in appearance to the active tablet but containing no active pharmaceutical ingredient. It is administered orally once daily to maintain blinding.

The placebo matching dapagliflozin is similarly a tablet identical in size, shape, and appearance to the Forxiga tablet, containing no active substance. It is taken orally once daily.

All study medications and placebos are dispensed in blister packs labeled with a unique participant identifier. Dosing compliance is monitored by pill count at each scheduled visit, participant self‑reported dosing diaries, and verification of adherence through electronic medication event monitoring systems where available. Missed doses are recorded, and participants are instructed to resume the scheduled dosing regimen the following day without double‑dosing.

Efficacy will be assessed by comparing the change from baseline to Week 40 in several glycemic and metabolic parameters. The primary endpoint is the change in HbA1c (%) from baseline to Week 40. Secondary endpoints include the same HbA1c change, the proportion of participants achieving HbA1c < 7 % (53 mmol/mol) at Week 40, percent change and absolute change in body weight (kg), change in fasting plasma glucose (FPG) from baseline to Week 40, change in the daily mean of a 7‑point self‑monitoring blood glucose (7‑point SMBG) profile, achievement of ≥ 5 % weight loss at Week 40, change in systolic and diastolic blood pressure (SBP and DBP) from baseline to Week 40, and time to initiation of rescue medication over the 40‑week period.

Laboratory assays validated for HbA1c and FPG will be performed on blood samples collected at screening, baseline, and Week 40. Body weight will be measured with a calibrated scale at the same visits. Blood pressure will be obtained using a validated sphygmomanometer. Participants will record SMBG values using a standardized glucometer according to a 7‑point schedule. All data will be analyzed according to the predefined statistical analysis plan, with comparisons made between the combination therapy and each monotherapy group.