Orforglipron: Farewell to Injections! The First Oral “Weight-Loss Miracle Drug” Comparable to Semaglutide

A Breakthrough in Diabetes and Obesity Treatment

With the global prevalence of diabetes and obesity continuing to rise, a revolutionary oral therapy is reshaping the treatment landscape. Orforglipron, a first-in-class, small-molecule, non-peptide oral GLP-1 receptor agonist, was originally discovered by Chugai Pharmaceutical (Japan) and licensed to Eli Lilly in 2018. Today, it is bringing new hope to hundreds of millions of patients worldwide.

The Evolution of GLP-1 Therapies

GLP-1 receptor agonists have already rewritten pharmaceutical history in the fields of weight management and diabetes care. Injectable therapies such as Semaglutide (Ozempic®, Wegovy®) and Tirzepatide (Mounjaro®, Zepbound®) have achieved remarkable commercial success due to their powerful glucose-lowering and weight-reduction effects. However, injections present challenges in terms of convenience and patient adherence.

This bottleneck has now been overcome with the emergence of Orforglipron. In April 2025, it became the first oral small-molecule GLP-1 receptor agonist to successfully complete Phase 3 clinical trials—a true milestone. Patients will finally be able to avoid the burden of daily injections, instead taking a once-daily oral dose without restrictions on food or water.

Small-Molecule Innovation: A New Era of GLP-1

The success of Orforglipron lies in its groundbreaking non-peptide small-molecule design. Compared with traditional peptide-based GLP-1 drugs, it offers several advantages:

• Oral Stability: Its small-molecule structure resists enzymatic degradation in the digestive tract, making oral delivery feasible.
• Manufacturing Efficiency: Small molecules are easier and less costly to produce, supporting large-scale commercialization and improving global accessibility.
• Pharmacological Strength: As a potent, biased partial agonist of the GLP-1 receptor with cAMP signaling selectivity, Orforglipron reduces receptor desensitization. Its half-life of 29–49 hours supports once-daily dosing, ensuring sustained therapeutic efficacy.

Impressive Clinical Results

Weight Management: In a 36-week Phase 2 trial, Orforglipron reduced body weight by 9.4% to 14.7%, compared with only 2.3% in the placebo group. Remarkably, 46%–75% of patients achieved more than 10% weight loss.

Diabetes Treatment: In the Phase 3 ACHIEVE-1 trial for type 2 diabetes, Orforglipron lowered HbA1c by 1.24 to 1.48 percentage points over 40 weeks, versus 0.41% with placebo—demonstrating robust glycemic control.

Redefining a Trillion-Dollar Market

With Orforglipron nearing commercialization, the GLP-1 therapeutic landscape is undergoing a paradigm shift. The global GLP-1 receptor agonist market is projected to grow from USD 53.46 billion in 2024 to USD 156.71 billion by 2030, representing a CAGR of 17.46%. Some forecasts predict the market may surpass USD 150 billion by 2030.

The availability of an oral formulation will not only advance technology but also expand patient access—especially for those unwilling or unable to use injections. Industry experts expect the first oral GLP-1 drug to enter the market in 2027, with Eli Lilly’s Orforglipron positioned as the clear frontrunner.

Competition, however, is intensifying. Currently, 63 GLP-1 receptor agonist programs are in development worldwide, with 4 already in Phase 3. Lilly plans to submit regulatory filings for Orforglipron in obesity by the end of 2025, followed by type 2 diabetes in 2026.

CATO: Supporting Quality Control in Oral GLP-1 Innovation

As Orforglipron moves toward commercialization as the first oral small-molecule GLP-1 drug, its quality control requirements are both novel and demanding:

• Non-peptide structural innovation creates new impurity profiling challenges.
• Oral formulations require higher purity standards.
• Dual indications in diabetes and obesity demand a more rigorous quality system.

To meet these challenges, CATO provides Orforglipron-related impurity reference standards, offering professional support to pharmaceutical companies and research institutions. Our solutions ensure compliance with international quality standards, accelerating development, regulatory approval, and clinical application.

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