Comprehensive Clinical Development Review: Lotiglipron (PF-07081532)

1. Introduction to Lotiglipron (PF-07081532)

Lotiglipron, identified by the code PF-07081532, was an investigational, orally administered, small-molecule therapeutic agent developed by Pfizer Inc..[1] It belongs to the glucagon-like peptide-1 receptor agonist (GLP-1 RA) class of drugs.[3] The intended therapeutic indications for lotiglipron were the management of Type 2 Diabetes Mellitus (T2D) and obesity.[1]

The development of lotiglipron represented an effort to provide a convenient oral alternative to the widely successful injectable peptide-based GLP-1 RAs, such as semaglutide and liraglutide, which dominate the treatment landscape for T2D and obesity.[2] Pfizer pursued the development of lotiglipron concurrently with another oral small-molecule GLP-1 RA, danuglipron (PF-06882961).[1] This parallel development strategy suggested a high perceived value in capturing a share of the oral metabolic drug market, while also acknowledging the inherent risks and challenges in bringing such a novel small-molecule agent through clinical trials successfully. Despite initial promise, the clinical development of lotiglipron was ultimately discontinued by Pfizer in June 2023 due to safety concerns.[1]

2. Mechanism of Action and Therapeutic Rationale