Executive Summary

On April 1, 2026, the oral small-molecule GLP-1 Orforglipron was approved, ushering the GLP-1 space into the oral era.

Novo Nordisk's oral product was approved earlier; more than fifteen Chinese companies are advancing clinical programs.

Market competition is intensifying.

Oral peptide delivery faces multiple technical hurdles; permeation enhancers are the mainstream solution today, while new technologies continue to iterate.

This article reviews delivery technologies and the competitive landscape, and analyzes Nanjing Zhihe's positioning.

1. Background: Opportunities in Oral Peptide Drugs

Peptide drugs sit between small molecules and large-molecule biologics and offer multiple advantages.

The global GLP-1 market is growing fast, but most products today are injectable, limiting user experience.

Oral delivery is the industry's direction but faces major technical hurdles.

(1) Three Physiological Barriers for Oral Peptides

1. GI enzymatic degradation; insufficient stability

Peptide drugs are susceptible to the GI acidic/alkaline environment and various enzymes, leading to hydrolytic cleavage and direct loss of activity.

Use non-natural amino acid substitutions to optimize the drug structure.

Use fatty-acid side-chain modification to improve enzymatic resistance.

Apply cyclization to stabilize the peptide structure.

2. Weak transmembrane permeability; difficult absorption

Peptides have a fixed molecular-weight range and poor lipophilicity, so they cannot cross GI epithelial cells efficiently, making absorption difficult.

Combine with permeation enhancers to assist absorption.

Apply nanocrystal technology to improve drug properties.

Modify active-transporter ligands to facilitate drug penetration.

3. Short plasma residence time; poor in-vivo performance

The small fraction of peptide that is absorbed is rapidly metabolized and cleared, leaving insufficient plasma residence time for stable efficacy.

Modify with fatty-acid side chains to bind endogenous albumin.

Apply PEGylation to extend duration of action.

Use Fc fusion proteins and sustained-release formulations to optimize efficacy duration.

2. Global R&D Landscape: Fierce Oral GLP-1 Competition

(1) The Two Approved Oral GLP-1 Drugs

1. Novo Nordisk oral semaglutide

In December 2025, this drug was approved in the United States for weight management and for reducing cardiovascular risk.

It uses the SNAC permeation enhancer for absorption, with clinical efficacy close to that of the injectable form.

2. Lilly Orforglipron

Orforglipron was approved in April 2026 as a non-peptide small-molecule agonist with oral absorption without permeation enhancers.

It delivers excellent weight-loss and glucose-lowering efficacy with fewer dosing restrictions; the China filing has been submitted.

(2) Chinese Pipeline Layout

More than fifteen Chinese companies are developing oral GLP-1 programs.

Development progress spans Phase III, Phase II, Phase I, and preclinical stages.

Phase III: Multiple lead programs from Huadong Medicine, Hengrui, and AstraZeneca are advancing steadily.

Phase II: Innovent and Sciwind Biosciences have multiple candidates progressing orderly.

Phase I / preclinical: CSPC and Hengrui have multiple candidates in early development.

3. Technical Hurdles and Breakthroughs: A Paradigm Shift

(1) Maturity of SNAC Permeation Enhancer

SNAC is currently the most widely used oral-peptide permeation enhancer in commercial products.

Leveraging a proprietary platform, it modulates gastric pH, encapsulates the peptide, and helps the drug cross the cell membrane for absorption.

However, it has shortcomings including low bioavailability and usage limitations.

(2) Multiple Novel Permeation Technologies Progress in Parallel

Beyond SNAC, fatty-acid salts, surfactants, cyclodextrin inclusion, and other routes continue to be refined.

These enrich the technology toolbox and improve oral peptide absorption from multiple angles.

(3) Breakthrough in Small-Molecule Agonists

Small-molecule non-peptide GLP-1 success breaks the conventional formulation-improvement mindset, achieving good oral efficacy from molecular design itself.

These molecules have appropriate MW, meet drug-like criteria, are easier to dose, and cost less to manufacture, offering strong overall advantages.

4. Closing

2026 marks the formal commercialization of oral GLP-1 drugs.

Traditional delivery is maturing and new small-molecule routes are becoming viable.

Now is the golden window for innovators to position in this space.

Nanjing Zhihe can seize the trend by building a proprietary platform and laying out oral innovative drugs early.

This will consolidate Zhihe's position in the hundred-billion-yuan pharmaceutical market and capture future opportunities.