Eli Lilly’s Orforglipron Shows Phase 3 Success: First Oral GLP-1 Drug for Type 2 Diabetes and Weight Loss

U.S. pharmaceutical giant Eli Lilly and Company announced good news on April 17 that its once-daily oral small molecule GLP-1 receptor agonist. Orforglipron has successfully met the primary endpoints in a key Phase 3 clinical trial. The investigational therapy demonstrated a safety and efficacy profile consistent with currently approved injectable GLP-1 drugs. It marks a significant milestone in the treatment of type 2 diabetes and obesity. Following the announcement, Lilly’s stock price surged by 14.30%, closing at $839.96 USD.

Designed to be taken once daily without food or water restrictions, Orforglipron could dramatically improve medication adherence and convenience for hundreds of millions of diabetes patients worldwide. According to estimates by the World Health Organization (WHO) and International Diabetes Federation (IDF), 760 million adults will be living with type 2 diabetes by 2050.

U.S. Manufacturing Strategy: Reducing Global Supply Chain Risks

In an exclusive interview, David A. Ricks, Lilly’s Chairman and CEO, emphasized that Orforglipron will be manufactured at Lilly’s upcoming API (Active Pharmaceutical Ingredient) facility — projected to be the largest in the United States. 

Lilly is actively expanding its U.S.-based manufacturing footprint to support drug supply security. According to Ricks, the company is building four new facilities across the United States, in states including Indiana, Wisconsin, and North Carolina, aiming to boost production capacity by more than 50%.

This capacity will not only support the production of Orforglipron, but also meet the growing global demand for other Lilly incretin-based drugs such as tirzepatide (Zepbound). Ricks emphasized that this is not only a matter of economic optimization, but also a strategic response to geopolitical and healthcare security concerns. During events such as pandemics or trade disruptions, domestic production can ensure consistent drug supply.

He also addressed challenges linked to current U.S. trade and tariff policies, particularly the pharmaceutical industry’s reliance on international suppliers. Many starting materials used in Lilly’s products still depend on Chinese chemical manufacturers, and potential trade conflicts or tariffs could significantly raise production costs and disrupt operations.

To mitigate these risks, Ricks called for a “friend-shoring” approach — bringing manufacturing back to the U.S. or to friendly allied regions. He urged the U.S. government to adopt positive incentive policies, such as tax credits and infrastructure grants, rather than punitive trade measures, in order to enhance the resilience and autonomy of the nation’s pharmaceutical supply chain.

ACHIEVE-1 Phase 3 Trial: Dual Benefits in Blood Sugar and Weight Control

ACHIEVE-1 is the first of seven Phase 3 trials in the Orforglipron clinical development program. The study evaluated adults with type 2 diabetes inadequately controlled through diet and exercise alone. Conducted over a 40-week period, the trial primarily assessed glycemic control (via A1C reduction) and monitored weight loss as a key secondary endpoint.

Orforglipron achieved statistically significant A1C reductions at all tested doses — 1.3% (3 mg), 1.6% (12 mg), and 1.5% (36 mg) from a baseline A1C of 8.0%, compared to only 0.1% in the placebo group. Notably, over 65% of patients receiving the highest dose achieved an A1C of ≤6.5%, the threshold defined by the American Diabetes Association (ADA) for diabetes diagnosis.

In terms of weight loss, Orforglipron also delivered impressive results. Participants began with an average baseline weight of 90.2 kg. Those on the highest dose (36 mg) lost an average of 7.3 kg — 7.9% of their total body weight — even before reaching a weight loss plateau. The 12 mg dose group lost 5.5 kg or 6.1%, while the placebo group lost only 1.3 kg or 1.6%.

Safety Profile Comparable to Injectable GLP-1s, No Liver Safety Concerns

Orforglipron’s safety and tolerability were comparable to established injectable GLP-1 therapies, with no liver toxicity signals observed during the trial. The most common side effects were gastrointestinal, including diarrhea (19–26%), nausea (13–18%), dyspepsia (10–20%), constipation (8–17%), and vomiting (5–14%), with most cases being mild to moderate. These adverse events were observed during early treatment and could be managed through dose adjustments.

Overall discontinuation rates due to side effects remained within acceptable levels: 6% (3 mg), 4% (12 mg), and 8% (36 mg), compared to 1% in the placebo group.

Regulatory Outlook: Weight Loss in 2025, Diabetes in 2026

The success of Orforglipron represents more than a scientific achievement — it could transform the delivery model for GLP-1 therapies. This will offer patients a needle-free, convenient oral option with comparable outcomes.

Lilly will present the full results of the ACHIEVE-1 study at the 85th Scientific Sessions of the American Diabetes Association (ADA) in 2025 and will submit them for peer-reviewed publication. Additionally, Lilly will release the results of the ATTAIN Phase 3 program—focused on Orforglipron’s effectiveness in weight management—later this year.

The company plans to submit regulatory filings for weight loss indications by the end of 2025, followed by type 2 diabetes indications in 2026.

If approved, Orforglipron could become a game-changer in the global fight against obesity and diabetes — offering powerful metabolic benefits through the simplicity of a daily pill.

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Author

Steven Chung

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