Could Eli Lilly's Oral GLP-1, Orforglipron, Be the Next Major Player in Weight Loss Therapy?

✎Dr. Katherine Gabriel, PharmD, RPh

ORCiD: 0009-0004-0341-9744

Background

The weight loss drug market is on fire, fueled by unprecedented demand and a surge of pharmaceutical ambition. With projections leaping from $6 billion in 2023 to $105 billion by 2030, the space has become the industry’s next battleground ¹. Now, Eli Lilly enters the ring with Orforglipron, its first oral GLP-1 candidate and a potential game changer in the fight for market share.

GLP-1s: The Game-Changer in Metabolic Health

Over the past few years, GLP-1 receptor agonists have upgraded from quiet contenders to headline makers and they are living up to the growing attention. These medications are changing the way that we treat Type 2 diabetes, obesity, and a range of metabolic conditions. But, what exactly are GLP-1s, and why are they such a big deal?

GLP-1s, short for glucagon-like peptide-1 receptor agonists, are a class of medications that mimic a hormone your body already makes to help regulate blood sugar and appetite. What makes them stand out is how they work across multiple systems in the body, subtly but powerfully. In the stomach, GLP-1s slow down how quickly food is digested, which helps prevent the blood sugar spikes that often follow meals. In the pancreas, they stimulate insulin, but only when it is actually needed, while dialing down glucagon, a hormone that can elevate blood sugar unnecessarily. And in the brain, GLP-1s promote a feeling of satiety, making it easier to consume less food without feeling deprived ².

Unlike conventional therapies, which often function as blunt instruments, including widespread systemic effects with limited precision, GLP-1 receptor agonists orchestrate a coordinated, multi-system response. By targeting critical points in appetite regulation, insulin sensitivity, and gastrointestinal function, they address the underlying drivers of metabolic dysfunction.

In the present day, medications like Ozempic, Wegovy, and Mounjaro are popular topics of conversation in both doctors’ offices and at the dinner table. While GLP-1 receptor agonists have conventionally been administered via injection, the approval of Rybelsus in 2019 as the first oral formulation by the FDA represents a pivotal development in the therapeutic landscape. Additionally, Orforglipron, an oral GLP-1 currently in development by Eli Lilly, is showing promising results in Phase 3 trials. Research in this area continues to evolve rapidly.

The results speak for themselves: many individuals experience 15-20% weight loss, improved blood sugar levels, and even protection for the hearts and kidneys³. For individuals living with Type 2 diabetes or struggling with obesity, GLP-1s offer a new kind of hope, one rooted in science, balance and long-term health.

In short, GLP-1s are not just another medication. They are a smarter, more personalized way forward in metabolic care.

Small Pill, Big Impact: The Promise of Orforglipron

The success of Orforglipron in Phase 3 trials marks a pivotal moment, not just for Eli Lilly, but for the future of obesity and diabetes care. As the final and most rigorous stage of clinical development, a positive Phase 3 outcome shows that Orforglipron has demonstrated both safety and efficacy at scale, overcoming the final major regulatory barrier on the path to FDA approval. While oral GLP-1s like Rybelsus exist, Orforglipron stands out for its once-daily dosing and non-peptide formulation, making it a potentially more convenient option for patients. For patients wary of needles or seeking more convenient options, Orforglipron could be a game-changer. Its efficacy isn’t just promising, it is proven, delivering statistically significant results in weight loss and blood glucose control that rival leading injectable therapies. Equally important, its safety profile aligns with the well-established standards of existing GLP-1s, reinforcing physician confidence in its potential as a safe and efficacious treatment option⁴. If approved, Orforglipron has the potential to reshape how metabolic diseases are treated, broadening access, improving adherence, and reinforcing Lilly’s leadership in one of the most competitive and high-impact areas of modern medicine.

The Final Word on Orforglipron

As the weight loss drug market accelerates into a new era, the arrival of Orfoglipron could mark a meaningful shift into how we approach obesity and metabolic disease. Its oral formulation, proven efficacy, and favorable safety profile elevate it beyond the role of an alternative, positioning it as a disruptive force in an injectable-dominated market. Upon regulatory approval, Orforglipron won’t just be another product on the shelf. It could expand access, enhance patient adherence, and further solidify GLP-1s as the cornerstone of modern metabolic care. For Eli Lilly, it is a strategic play. For patients, it might just be a simpler, smarter path to long-term health.  Only time and regulators will tell, but all signs point to Orforglipron becoming a major player in the next chapter of weight loss therapy.

References

1. Morgan Stanley. Obesity Drugs’ Ripple Effects | Morgan Stanley. Morgan Stanley. Published 2024. https://www.morganstanley.com/ideas/obesity-drugs-market-expanded-opportunity

2. ‌Collins L, Costello RA. Glucagon-like peptide-1 receptor agonists. PubMed. Published February 29, 2024. https://www.ncbi.nlm.nih.gov/books/NBK551568/

3. Jan 11 EGB / P, 2024. The pros, cons, and unknowns of popular weight-loss drugs. The Hub. Published January 11, 2024. https://hub.jhu.edu/2024/01/11/ozempic-wegovy-weight-loss-drugs-pros-cons/

4. ‌Lilly’s oral GLP-1, orforglipron, demonstrated statistically significant efficacy results and a safety profile consistent with injectable GLP-1 medicines in successful Phase 3 trial | Eli Lilly and Company. Eli Lilly and Company. Published 2024. https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-demonstrated-statistically