For years, the conversation around medical treatments for obesity and type 2 diabetes has revolved around injectables such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound). Now, the future may fit inside a pill.
In late August, pharmaceutical giant Eli Lilly announced breakthrough results from late-stage trials of orforglipron, its experimental oral GLP-1 receptor agonist. The findings represent a significant step toward making weight-loss and diabetes care more accessible to millions of patients worldwide who have been hesitant about injections.
The Study in Numbers
The Phase 3 trial followed overweight adults with type 2 diabetes for 72 weeks. Patients who took orforglipron once daily lost an average of 10.5% of their body weight—about 23 pounds—compared to just 2.2% in the placebo group.
The benefits extended well beyond weight loss. Roughly 75% of participants on the highest dose reached an A1C of 6.5% or lower, the threshold considered well-controlled diabetes. For patients struggling with both weight and blood sugar management, this could be a game changer.
Tolerability and Side Effects
As with other GLP-1 therapies, gastrointestinal issues were the most common side effects. About one-third of participants reported nausea, nearly a quarter experienced vomiting, and around 10% discontinued treatment. These rates are broadly comparable to injectable GLP-1 drugs already on the market.
What It Is and How It Works
Orforglipron is a once-daily, oral, non-peptide GLP-1 receptor agonist. Unlike injectable GLP-1 drugs, it is a small molecule that can be taken at any time of day, with or without food or water.
In the Phase 3 ATTAIN-2 trial, in adults with obesity/overweight and type 2 diabetes, orforglipron achieved 10.5% weight loss at 72 weeks, A1C reductions of –1.3% to –1.8%, and 75% of patients reaching an A1C ≤ 6.5% at the highest dose. The safety profile was consistent with the GLP-1 class, dominated by mild-to-moderate gastrointestinal symptoms and discontinuation rates of 6–11%.
Because it is a small-molecule pill rather than a peptide injection, orforglipron is easier to manufacture and distribute, potentially improving access worldwide.
Market Impact
The global obesity and diabetes drug market is booming, projected to reach $150 billion by the early 2030s. Analysts believe an effective oral GLP-1 could broaden the reach of the class dramatically, especially in lower-income countries where injectable storage and administration pose barriers.
While orforglipron’s weight-loss results were slightly behind Novo Nordisk’s Wegovy, analysts still see strong commercial potential. Lilly has already begun stockpiling supply ahead of launch to avoid early shortages.
Orforglipron is being developed for both weight management in adults with obesity/overweight (with and without diabetes) and for type 2 diabetes treatment. It is also under investigation for obesity-related sleep apnea and hypertension.
Pricing and Access
Lilly has pledged to set orforglipron’s price “based on value” and to offer direct-to-consumer programs to help bridge gaps in insurance coverage for obesity treatment. No official price has been announced, but expectations are that, as a small molecule, it will be less costly to produce and distribute than injectable peptides.
For comparison:
Wegovy (semaglutide 2.4 mg): list price of $1,349/month in the U.S.
Ozempic (semaglutide for diabetes): around $499/month through some cash-pay programs.
Regulatory Outlook
Lilly plans to submit orforglipron for approval in 2025. The company has confirmed it is already manufacturing supply to avoid shortages at launch. If approved, orforglipron would be the first oral GLP-1 therapy for obesity and a strong contender in a market that is redefining the way the world approaches weight loss and diabetes.
SOURCE: Eli Lilly
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