Danuglipron
Metabolic / Weight LossAlso known as: PF-06882961, Pfizer Danuglipron
Mechanism
Danuglipron is an oral, non-peptide small molecule that activates the same GLP-1 receptor as injectable semaglutide. Unlike peptide-based GLP-1 drugs that must be injected or specially formulated for oral use, danuglipron is a traditional pill. It reduces appetite, improves blood sugar control, and promotes weight loss, though gastrointestinal side effects remain common.
Technical detail
Danuglipron is a non-peptide, small-molecule oral GLP-1R agonist. It binds the extracellular domain of GLP-1R and activates Gs-coupled cAMP signaling in pancreatic beta cells, promoting glucose-dependent insulin secretion. Despite being a non-peptide, it achieves full GLP-1R agonism with biased signaling profiles that may differ from native GLP-1. Oral bioavailability eliminates the need for injection or permeation enhancers required by oral semaglutide. Twice-daily dosing in current formulations.
Evidence
- strong
Saxena AR et al. (2023) — JAMA Netw Open — PMID: 37213102
16-week phase 2b randomized trial in 411 adults with type 2 diabetes showed statistically significant HbA1c and fasting glucose reductions across danuglipron doses, plus body-weight loss up to 4.17 kg versus placebo at 120 mg BID; nausea, diarrhea, and vomiting were common adverse events.
- strong
Saxena AR et al. (2023) — Diabetes Obes Metab — PMID: 37311722
12-week randomized placebo-controlled phase 2 study found danuglipron reduced HbA1c by about 1.04%-1.57%, lowered fasting glucose, and reduced body weight by 1.93-5.38 kg, but with higher discontinuation and gastrointestinal adverse-event rates at higher target doses.
- moderate
Saxena AR et al. (2021) — Nat Med — PMID: 34127852
Multiple ascending-dose phase 1 trial in type 2 diabetes found danuglipron generally well tolerated over 28 days, with mostly mild gastrointestinal adverse events and no clinically meaningful laboratory or ECG safety signal.