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Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity NEJM : DOI: 10.1056/NEJMoa2302392 Orforglipron es un agonista oral no peptídico del receptor GLP-1 que se está desarrollando para el control del peso y el tratamiento de la diabetes tipo 2. Orforglipron actúa como un potente agonista parcial del receptor GLP-1. GLP-1 (Péptido similar al glucagón-1) es una hormona que juega un papel en la regulación de la glucosa y el control del apetito. Orforglipron tiene un mecanismo único de activación del receptor GLP-1. Produce señalización cAMP similar a la producida por el GLP-1 nativo. Sin embargo, conduce a una baja activación de la vía β-arrestina, que regula la internalización del receptor. Este efecto de señalización sesgada puede contribuir a su eficacia. 272 participantes fueron asignados aleatoriamente para recibir diferentes dosis de orforglipron: 12 mg, 24 mg, 36 mg, etc. Participantes del Estudio: El estudio se centró en participantes que tenían obesidad (índice de masa corporal IMC 30) o estaban con sobrepeso (IMC entre 27 a 30) con al menos una condición relacionada con el peso, como hipertensión, dislipidemia, enfermedad cardiovascular o apnea obstructiva del sueño. Se requería que los participantes tuvieran un peso corporal estable (5% de ganancia o pérdida) durante los 3 meses anteriores a la aleatorización. Semana 26: Orforglipron 12 mg: -9.0 kg Orforglipron 24 mg: -12.3 kg Orforglipron 36 mg: -12.9 kg Orforglipron 45 mg: -13.3 kg Placebo: -2.1 kg Semana 36: Orforglipron 12 mg: -9.8 kg Orforglipron 24 mg: -13.6 kg Orforglipron 36 mg: -14.2 kg Orforglipron 45 mg: -15.4 kg Placebo: -2.4 kg Estos valores representan el cambio medio estimado en el peso corporal desde el inicio para cada grupo. Se observó que la reducción de peso dependía de la dosis, con dosis más altas de Orforglipron resultando en una mayor pérdida de peso en comparación con el grupo placebo.