An experimental oral GLP-1 receptor agonist, orforglipron, achieved superior glycaemic control compared with the SGLT2 inhibitor dapagliflozin in a phase 3 trial involving adults with type 2 diabetes inadequately managed with metformin. The findings, published in The Lancet, offer a potential new oral option for patients who need better blood sugar management.
The ACHIEVE-2 trial enrolled 1,200 participants across multiple centres in an open-label, non-inferiority design. Orforglipron belongs to a drug class that has transformed diabetes and obesity care, but most current GLP-1 therapies require injection. An oral formulation could expand access and patient adherence.
The agent's tolerability profile aligned with expectations for GLP-1 receptor agonists, including gastrointestinal side effects and increased rates of discontinuation due to adverse events. While orforglipron met its primary efficacy endpoint, the trial's open-label design introduces potential bias.
Regulatory filings are expected later this year. If approved, orforglipron would compete with oral semaglutide in the growing oral GLP-1 market. Analysts see blockbuster potential but caution that tolerability and real-world adherence remain open questions.
Some clinicians note that injectable GLP-1 formulations have already shown strong cardiovascular benefits, a benchmark oral agents have yet to match.