Orforglipron, a new oral tablet GLP-1 receptor agonist, has shown better glycemic control and weight loss in patients with type 2 diabetes compared to oral semaglutide (Rybelsus).[1][2] In the phase 3 ACHIEVE-3 trial of 1698 patients inadequately controlled on metformin after 52 weeks, orforglipron 36 mg achieved a 2.2% reduction in HbA1c, while semaglutide 14 mg achieved a 1.4% reduction.[3][5] Patients on orforgliprone 36 mg lost an average of 9.2% of body weight (8.9 kg), compared to 5.3% (5.0 kg) on semaglutide.[3][2] Up to 37.1% of patients on the highest dose of orforglipron achieved HbA1c below 5.7%, compared to 12.5% on semaglutide.[3][5] Orforglipron can be taken with or without food, unlike semaglutide, which requires taking it on an empty stomach.[1][9] The study was funded by Eli Lilly, the manufacturer of orforglipron, and the results published in The Lancet.[1][2] Treatment had mainly gastrointestinal side effects, with discontinuation in 9.7% of patients on the 36 mg dose versus 4.9% on semaglutide.[4] Orforglipron is under review in the US, with registration in type 2 diabetes expected later in 2026.[4]