Orforglipron: What to Know About Eli Lilly's New Weight Loss Pill for Obesity

Health Line

3 days ago

Eli Lilly's new oral GLP-1 medication orforglipron produced an average weight loss of 12.4% (27.3 pounds) in clinical trials.
The weight loss pill also significantly improved heart health markers like cholesterol and blood pressure.
Experts note that some may prefer the flexibility of a weight loss pill compared to the injectable version.
Eli Lilly is on track to apply for FDA approval by late 2025, the drugmaker announced.
A groundbreaking new oral medication for weight management has shown promising results in a recent large-scale clinical trial, offering hope to millions with obesity and related health issues.
Orforglipron, developed by Eli Lilly, is an investigational daily pill that mimics the effects of injectable GLP-1 receptor agonists, a class of drugs known to help with weight loss and blood sugar control.
In its pivotal Phase 3 ATTAIN-1 trial, which involved over 3,000 adults with obesity or overweight, orforglipron demonstrated significantly higher weight loss compared to a placebo.
Participants titrating up to the highest dose of 36 milligrams lost an average of 12.4% of their initial body weight (27.3 pounds) over the course of the 72-week study.
Lower doses (6 milligrams and 12 milligrams) also showed clinically significant weight reductions of 7.8% and 9.3%, respectively.
Beyond weight loss, orforglipron improved heart health markers while maintaining a safety profile similar to existing treatments. These improvements included lower levels of non-HDL cholesterol, triglycerides, and systolic blood pressure. At the highest dose, it also reduced high-sensitivity C-reactive protein (hsCRP) by 47.7%
With regulatory submissions planned by the end of 2025 and a global launch on the horizon, here is everything you need to know about the new weight loss pill from Eli Lilly.
What is orforglipron?
Injectable glucon-like peptide-1 (GLP-1) medications have skyrocketed in popularity due to their clinically significant effects on weight loss and the management of certain health conditions.
This class of drugs, sometimes referred to as GLP-1 receptor agonists, includes Wegovy (semaglutide) and Zepbound (tirzepatide). Diabetes medications Ozempic and Mounjaro are often prescribed off-label for weight management.
Unlike injectable GLP-1 drugs, orforglipron is not a peptide. Peptides are naturally occurring short chains of amino acids whose synthetic versions have found applications in many areas, such as skin care, bodybuilding, and weight loss, due to their ability to trigger desirable effects in the human body.
While orforglipron is not a peptide, it can activate the glucagon-like peptide-1 receptor in the same way as GLP-1 medications.
'Orforglipron is a new kind of GLP-1 medication known as a small-molecule oral GLP-1 receptor agonist,' explained Rekha Kumar, MD, an obesity medicine specialist and head of medical affairs at Found.
This means orforglipron can be taken in pill form to achieve similar effects, including weight loss and other improvements in metabolic health, like better blood sugar control, lower blood pressure, and reduced cholesterol.
Are weight loss pills as effective as injectable GLP-1s?
Once-daily oral versions of GLP-1 drugs could replace the need for once-weekly injections, but Eli Lilly isn't the only drug manufacturer with a weight loss pill in the works.
Competitor Novo Nordisk's weight loss pill has also produced meaningful weight loss results in clinical trials. The Food and Drug Administration (FDA) recently accepted Novo Nordisk's application to produce its oral version of Wegovy.
While clinical trials for both drugmakers' weight loss pills have yielded positive results for weight loss, experts say they may not always be as effective as injectable counterparts.
'That's because orforglipron is a non-peptide, small-molecule pill, so it doesn't bind to the GLP-1 receptor quite as strongly as injectable peptide medications, which mimic our body's natural GLP-1 hormone,' Kumar explained.
'Even so, the results are still very good by any health standard, and for people who prefer a pill over an injection, it's an effective alternative to help reach weight-care goals,' Kumar told Healthline.
Some people might prefer weight loss pills over injectables
Some people may prefer current injectable GLP-1 medications due to their potential for greater weight loss or the simplicity of weekly injections.
For others, the convenience of a once-daily pill like orforglipron might seem more appealing.
Kumar noted that many people might prefer a pill over needles, or not having to worry about refrigeration or structured rules about when to inject the medication.
According to Eli Lilly's press release, orforglipron can be taken at any time of the day without restrictions on food and water intake.
'It's a great option for people who want a simpler, needle-free treatment that fits easily into busy or unpredictable schedules — like parents, frequent travelers, or anyone who dislikes injections,' Kumar said.
There are also the dual factors of cost and availability.
Kumar said you can 'expect manufacturing and storage to be easier and cheaper for a pill like this, so once someone starts, they're less likely to face the shortages we saw after Wegovy and Zepbound launched.'
This could make orforglipron more accessible to many people, Kumar noted.
Side effects of weight loss pill similar to other GLP-1s
Meghan Garcia-Webb, MD, triple board certified in internal medicine, lifestyle medicine, and obesity medicine, and an internist at an academic medical center in Boston, noted that orforglipron has shown potentially mild to moderate gastrointestinal side effects.
These include nausea, vomiting, constipation, and diarrhea.
As Eli Lilly stated in a press release, this is consistent with the overall safety profile of other drugs in this class.
About 1 in 10 individuals at the highest tested dose dropped out of the study due to these adverse effects.
Importantly, Eli Lilly also stated that there were no observed signs of liver-related side effects.
'Overall it seems like a very promising alternative offering similar results to Wegovy with a similar side effect profile to current GLP-1 RA weight medications,' said Garcia-Webb.
When will Lilly's weight loss pill be available?
Eli Lilly announced they're planning to submit orforglipron to the FDA for weight loss this year. Garcia-Webb said this means the pill could be approved as early as 2026.
The drugmaker stated that Orforglipron's positive Phase 3 ATTAIN-1 trial results have put it on track to submit to global regulatory agencies by the end of 2025.
They are also making substantial investments to meet anticipated demand at launch. This indicates that orforglipron could become available to consumers following regulatory approval.
However, Eli Lilly cautions about the risks and uncertainties in drug development. There are no guarantees that orforglipron will be approved or make it to market on the anticipated timeline.
In the meantime, Novo Nordisk's weight loss pill could come to market sooner, but an exact timeline remains unclear.