Oral GLP-1 Receptor Agonist Bofanglutide Shows Promising Results
Key Clinical Summary
- Oral bofanglutide demonstrated dose-dependent pharmacokinetics and robust weight reduction after 14 days of treatment.
- No serious adverse events were reported; mild gastrointestinal symptoms were the most common side effects.
- A 60-minute post-dose fasting interval enhanced drug exposure by approximately 60% compared to 30 minutes.
At ObesityWeek 2025, researchers presented encouraging results on the pharmacokinetics, pharmacodynamics, safety, and bioavailability of the oral GLP-1 receptor agonist, bofanglutide. In this first-in-human trial, oral bofanglutide demonstrated favorable exposure levels, a predictable safety profile, and clinically relevant reductions in fasting plasma glucose (FPG) and body weight.
Session Highlights
In the poster session Oral-001, researchers detailed a randomized, open-label, 2-part study evaluating the safety, bioavailability, and pharmacologic profile of oral bofanglutide co-formulated with the absorption enhancer SNAC.
Part A of the study assessed single ascending doses (30, 60, 90 mg) of oral bofanglutide in 44 healthy males and compared them to a 0.6 mg subcutaneous injection. Results showed dose-proportional increases in exposure. The AUC₀–ₜ values ranged from 3,980.76 to 28,180.67 h•ng/mL and Cₘₐₓ from 40.95 to 254.47 ng/mL across oral doses.
Part B involved 48 subjects who received daily oral bofanglutide with varying fasting intervals post-dose (30 or 60 minutes). Bofanglutide exposure increased by ~60% in the 60-minute group for both AUC₀–ₜ and Cₘₐₓ (p = 0.008 and p = 0.011, respectively). The mean half-life across all groups was approximately one week. Notably, subjects in the 60-minute group experienced a 4.16% mean reduction in body weight over 14 days, with weight loss continuing after treatment cessation.
No severe hypoglycemic events or serious adverse events (SAEs) were reported. Mild gastrointestinal disturbances were the most common adverse events (AEs), consistent with the GLP-1 RA class.
Expert Perspectives
Study investigators emphasized the potential clinical relevance of a once-daily oral GLP-1 receptor agonist formulation. “These findings represent a meaningful step toward expanding GLP-1 RA options for patients who prefer oral administration,” said the researchers, highlighting the importance of optimizing post-dose fasting intervals to maximize therapeutic exposure.
Experts noted the clinical implications of the significant pharmacokinetic differences between 30- and 60-minute fasting windows. “The ~60% increase in bioavailability with a 60-minute fast may allow better glycemic control and weight outcomes without compromising tolerability,” a co-investigator added.
Additionally, the trial supports the rationale for continued development of oral bofanglutide for indications such as type 2 diabetes and obesity, where GLP-1 RAs have become key components of care.
Implications for Practice
These findings underscore the feasibility of once-daily oral GLP-1 receptor agonist therapy in clinical settings, offering a new administration route with a favorable safety profile. The dose-response relationship and post-dose timing effects may inform future dosing guidelines and patient adherence strategies.
Conclusion
The first-in-human study of oral bofanglutide demonstrated favorable pharmacokinetics, robust weight loss, and a predictable safety profile. These results support the continued development of oral bofanglutide as a viable alternative to injectable GLP-1 RAs for type 2 diabetes and weight management.
Reference
Hao X, Zhao J, Min X, et al. Poster-315 bioavailability, PK, PD, and safety of the oral GLP-1 RA, Bofanglutide tablet, in healthy subjects. Presented at the ObesityWeek; November 4-7, 2025. Atlanta, Georgia.
