In a major development for obesity and metabolic health treatment,Eli Lilly’s experimental oral GLP-1 therapy, orforglipron, demonstrated superior results compared withoral semaglutide (Wegovy)in a largePhase 3 head-to-head trialinvolving nearly 1,700 participants with type 2 diabetes and overweight conditions. TheACHIEVE-3study, published inThe Lancet, showed that orforglipron — taken once daily — delivered significantly greater improvements inweight loss and blood sugar controlcompared with semaglutide at key measured doses, with results emerging as early as four weeks and sustained throughout the study period.
Participants receiving orforglipron experienced more substantial average weight reduction and larger drops inA1C(a key marker of blood glucose levels) than those on the semaglutide regimen, highlighting its potential dual benefit in metabolic and obesity management. Unlike semaglutide, which is often taken under fasted conditions, orforglipron does not require fasting before dosing, offering easier administration for patients. While exact regulatory timelines are pending, orforglipron’s performance positions it as a strong candidate to expand the oral GLP-1 therapeutic landscape if approved for obesity indications.
Experts note that this milestone underscores intense competition in the weight-loss drug market, where multiple companies are racing to develop effective, convenient, and accessible oral treatments. Patients seeking options beyond injectable therapies — such as weekly GLP-1 injections — may benefit from the emerging crop of oral agents, but the long-term safety profiles and regulatory decisions will be key to widespread adoption.
