Oral glucagon-like peptide-1 receptor agonists may expand treatment options for type 2 diabetes mellitus (T2DM) by offering effective glycemic control without injection requirements. A Phase 2b trial published in The Lancet evaluated the efficacy, safety, and tolerability of once-daily oral elecoglipron in adults with T2DM.

This randomized, double-blind, placebo-controlled study enrolled adults with T2DM inadequately controlled with diet and exercise alone or monotherapy with metformin or a sodium-glucose cotransporter-2 (SGLT2) inhibitor. Participants were randomized to multiple elecoglipron dosing regimens, matched placebo, or open-label oral semaglutide for 26 weeks. The primary endpoint was change in glycated hemoglobin (HbA1c) from baseline to week 26.

Findings

• Among 404 participants who received treatment, mean baseline HbA1c was 7.9%, body weight was 99.8 kg, and body mass index was 34.9 kg/m².
• At week 26, HbA1c reductions with elecoglipron ranged from −0.91% (95% CI, −1.25 to −0.58) with the 5 mg dose to −1.88% (95% CI, −2.23 to −1.53) with the 75 mg dose using a 2-week dose-escalation schedule.
• The placebo group showed an HbA1c change of −0.15% (95% CI, −0.42 to 0.12).
• Adverse events were reported in 63% to 87% of participants receiving elecoglipron compared with 63% of those receiving placebo.
• The most common adverse events were gastrointestinal and included nausea, constipation, diarrhea, and vomiting.

This Phase 2b trial showed clinically meaningful, dose-dependent reductions in HbA1c with once-daily oral elecoglipron in adults with T2DM. The safety profile was consistent with that of the GLP-1 receptor agonist class, supporting further evaluation in Phase 3 clinical trials.