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Eli Lilly’s Oral Obesity Pill Shows Promising Results in Late-Stage Trial
PoraShuno Health Update | August 2025
Pharmaceutical giant Eli Lilly has announced encouraging results from its late-stage clinical trial of orforglipron, its experimental daily oral pill for obesity. The highest dose of the drug helped patients lose nearly 12% of their body weight, or approximately 27 pounds, over a period of 72 weeks.
While analyzing the full set of participants — including those who discontinued treatment — the average weight loss stood at 11.2%. This marks a significant advancement in the weight loss drug market, particularly as it offers a needle-free alternative to currently available injectable treatments.
Market Reaction and Analyst Expectations
Despite the strong results, Eli Lilly’s shares dropped over 13% in premarket trading following the announcement. Analysts had anticipated weight loss figures closer to 15%, aligning with the results achieved by Novo Nordisk’s injectable GLP-1 drug Wegovy, a leading product in the market.
Some healthcare professionals noted that although orforglipron’s efficacy is slightly lower than injectables, it remains a clinically meaningful achievement for an oral medication.
“This is a strong and promising result for an oral agent,” said Dr. Jaime Almandoz, Director at UT Southwestern Medical Center. “It reinforces the potential for an oral GLP-1 to be transformative in obesity care, particularly for patients hesitant to take injections.”
Discontinuation and Side Effects
One concern highlighted in the trial was the discontinuation rate due to side effects. About 10.3% of patients on the highest 36mg dose stopped treatment, compared to 2.6% in the placebo group. The most common side effects were gastrointestinal, including:
- Vomiting (24%)
- Nausea (33.7%)
- Diarrhea (23.1%)
Analysts had anticipated lower side effect-related dropout rates. For comparison, Wegovy and Eli Lilly’s injectable Zepbound show discontinuation rates of 7% or less.
“Nearly a quarter of patients on the highest dose discontinued the pill for any reason, which may temper the current enthusiasm,” cautioned Dr. Caroline Apovian of Brigham and Women’s Hospital.
Strong Efficacy Indicators
Despite concerns, the pill achieved notable success in other key metrics:
- 59% of patients lost at least 10% of their body weight
- 39% lost at least 15%
These results were described as “very impressive” by experts, especially given the oral form of administration. The drug also showed promise in reducing cardiovascular risk factors.
“Prescribing decisions will depend on individual patient needs,” said Dr. Almandoz. “While some may prefer injectables for more weight loss or cardiometabolic improvements, others may prioritize the simplicity of a daily pill.”
Regulatory Path and Market Impact
Eli Lilly plans to submit data to regulators by the end of 2025, with a projected market launch in 2026. According to Ken Custer, President of Lilly Cardiometabolic Health, orforglipron has the potential to fundamentally reshape the obesity treatment landscape.
There are currently 8 million patients on injectable GLP-1 drugs, but over 170 million could benefit from such medications globally. An oral formulation like orforglipron could:
- Ease manufacturing and supply constraints
- Reach patients wary of injections
- Reduce logistical challenges in distribution
“We’ll need options like oral small molecules that don’t rely on sophisticated cold-chain supply systems,” Custer stated.
Affordability and Access
Cost is a critical factor. Current injectable GLP-1s like Wegovy retail at approximately $1,000/month before insurance, largely due to device costs. Experts like Dr. Amy Sheer from the University of Florida hope that an oral option will:
- Be more affordable
- Encourage insurance coverage
- Improve patient access, especially in underserved populations
She also noted that some physicians are hesitant to prescribe injectables due to lack of training, but a pill format could increase their willingness to offer GLP-1 therapies.
Looking Ahead
Detailed findings from the orforglipron trial will be presented at a European medical conference in September and published in a peer-reviewed journal. Additional phase three trial data is expected later this year, including results from patients with Type 2 diabetes.
Orforglipron works by targeting the GLP-1 gut hormone, similar to Wegovy and Novo Nordisk’s Rybelsus, but with a key difference — it is not a peptide medication. This gives it advantages in absorption and flexibility, as it doesn’t require the same dietary restrictions as Rybelsus.
Currently, Eli Lilly leads the race among companies developing oral weight-loss pills, ahead of competitors like Pfizer, AstraZeneca, Roche, and others.
Analysts forecast the GLP-1 drug market could exceed $150 billion annually by the early 2030s, with oral GLP-1s accounting for $50 billion of that.
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