Efficacy and Safety of Oral Orforglipron in Patients with Type 2 Diabetes: A Multicentre, Randomised, Dose-Response, Phase 2 Study
Lancet. 2023. DOI: 10.1016/S0140-6736(23)01302-8
Orforglipron, an oral, non-peptide GLP-1RA, was assessed at various once-daily doses (3 mg, 12 mg, 24 mg, 36 mg, 45 mg) and dose-escalation schedules vs placebo and dulaglutide in 383 patients with T2D, with or without metformin, and BMI ≥23 kg/m2, with no food or water restrictions.
At doses of 12 mg or greater, once-daily orforglipron showed significant reductions in HbA1c and bodyweight compared with placebo or dulaglutide. At week 26, mean change in HbA1c with orforglipron was up to −2.10% vs −0.43% with placebo and −1.10% with dulaglutide. Change in mean bodyweight at week 26 was up to −10.1 kg with orforglipron vs −2.2 kg for placebo and −3.9 kg for dulaglutide. The incidence of AEs ranged from 61.8−88.9% in orforglipron-treated participants, compared with 61.8% with placebo and 56.0% with dulaglutide. High rates of treatment discontinuation and frequent GI AEs (44.1−70.4% with orforglipron, 18.2% with placebo and 34.0% with dulaglutide) were observed with orforglipron, particularly with rapid dose escalation.
The authors concluded that orforglipron might provide an alternative to injectable GLP-1RAs and oral semaglutide.
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