Phase III Randomized, Double‑Blind, Parallel‑Group Study of Elecoglipron Added to Dapagliflozin in Adults with Type 2 Diabetes Mellitus and Impaired Renal Function

Primary objective: To assess the efficacy of elecoglipron dose A and dose B compared with placebo, when added to dapagliflozin 10 mg, in improving glycemic control in adults with type 2 diabetes mellitus and impaired renal function, thereby addressing the need for additional glucose‑lowering options in this high‑risk population.

Secondary objectives:

• Evaluate the effect of elecoglipron dose A and dose B versus placebo on body‑weight reduction, systolic blood pressure reduction, and glycemic control.
• Assess the impact on the requirement for rescue medication, diastolic blood pressure reduction, and glycemic control.
• Characterize safety and tolerability, including adverse‑event incidence and laboratory safety markers.

The trial enrolled 717 participants diagnosed with type 2 diabetes mellitus. Both female and male adults were included, covering the age categories represented by codes 3 and 4. Eligible individuals had a documented diagnosis of T2DM for at least 90 days, were either on a stable dose of an SGLT2 inhibitor or SGLT2i‑naïve, and presented a baseline HbA1c of 7.0%–10.5% (or 7.5%–10.5% if naïve). Additional inclusion requirements were a body‑mass index of ≥23 kg/m², stable body weight for the preceding 90 days, impaired renal function, and use of no more than one other glucose‑lowering medication. The study population comprised patients, including individuals classified as vulnerable, without specific restrictions on diet or physical‑activity habits beyond the stability criteria. Selection was based on meeting these predefined inclusion parameters; exclusion criteria were not detailed in the source information.

The study is a Phase III, randomized, double‑blind, parallel‑group trial evaluating two dose levels of elecoglipron versus placebo, each administered in combination with dapagliflozin 10 mg daily, in adults with type 2 diabetes mellitus and impaired renal function. After an eligibility screening visit, participants are randomized to one of three arms and receive study medication for 40 weeks, with scheduled follow‑up visits at Weeks 4, 12, 24, and 40 to assess efficacy (primary endpoint: change in HbA1c from baseline to Week 40) and safety; a final end‑of‑study visit occurs at Week 40. Total participant involvement therefore spans approximately 42 weeks, including screening. Early termination may occur if a participant experiences a serious adverse event, requires rescue medication, withdraws consent, or violates major protocol criteria.

The investigational product Elecoglipron is provided as a film‑coated tablet for oral use, supplied at a dose of 00 mg per tablet. Participants receive the assigned dosage of Elecoglipron in accordance with the randomization schedule; the tablet is taken by mouth.

All participants continue background therapy with dapagliflozin (Forxiga) administered as a 10 mg film‑coated tablet, taken orally. This standard‑of‑care agent is maintained throughout the study period.

The control arm utilizes a matching placebo for Elecoglipron (AZD5004). The placebo has no active substance, is presented in a tablet form identical to the active product, and is administered orally following the same dosing schedule as the active comparator.

Efficacy will be assessed by measuring the change from baseline to Week 40 in the primary parameter, HbA1c (%). The analysis will compare the mean change for each dose of elecoglipron with placebo while participants continue background dapagliflozin therapy.

Secondary efficacy assessments include the proportion of participants achieving HbA1c < 7% (53 mmol/mol) or ≤ 6.5% (48 mmol/mol) at Week 40, the percent and absolute change in body weight (kg) from baseline to Week 40, the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to Week 40, the proportion achieving HbA1c < 7% without hypoglycemia (glucose < 54 mg/dL or severe hypoglycemia) at Week 40, the change in fasting plasma glucose (FPG) from baseline to Week 40, and the time to initiation of rescue medication over the 40‑week period. All parameters will be evaluated using the values recorded at baseline and at the Week 40 visit.