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What is Orforglipron?
Medically reviewed by
Craig Marsh, Specialist Pharmacist Prescriber (UK)
It’s still under development as an oral pill that’s taken once daily. But its manufacturer, Eli Lily (the company that makes Zepbound), expects it to be on the market by late 2026.
Table of contents
Medically reviewed by
Mr Craig Marsh
Specialist Pharmacist Prescriber (UK)
on May 07, 2025.
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Last updated on Feb 27, 2026.
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- Orforglipron is an oral once-daily medication for weight loss and type 2 diabetes.
- In clinical trials, Orforglipron helped participants lose up to 14.7% of their body weight, or around 34 lbs.
- Research suggests it may also help with liver, kidney, and heart disease.
- It hasn’t been approved yet, but may become available in 2026.
How is Orforglipron different from current GLP-1 medications?
Unlike many GLP-1s for weight loss, which are injected, Orforglipron will be available as a pill you take every day. This is made possible because Orforglipron is a small molecule, while current GLP-1 RAs are peptides (proteins). Peptides are easily broken down in your digestive system, so they’re usually given as injections.
For the same reason, Orforglipron is likely to be cheaper and more easily accessible. Since it’s a small, non-peptide molecule, it’ll be easier and potentially cheaper to produce and package into a pill (rather than an injection like Wegovy and Zepbound).
How does Orforglipron work?
Orforglipron is a GLP-1 receptor agonist, which means it activates the same receptors as a hormone found naturally in your body called GLP-1, mimicking its effects in your body. These include:
- Increased insulin secretion: Insulin is a hormone that helps your body use glucose (a type of sugar) for energy. Orforglipron increases insulin production, allowing muscles and the liver to use glucose more effectively. This leads to improved blood sugar control, which can reduce cravings and help treat diabetes.
- Decreased glucagon secretion: Orforglipron reduces the release of glucagon, a hormone that signals the liver to produce glucose. With less glucagon, the liver makes less sugar, helping to lower blood sugar levels.
- Delayed gastric emptying: GLP-1RAs reduce stomach contractions and slow down how quickly food travels from your stomach to your gut. This helps you feel full after eating less, which can lead to reduced food intake. But this can also cause side effects like nausea, bloating, and stomach discomfort.
- Decreased appetite: Orforglipron works on your brain to increase feelings of fullness and satiety while reducing hunger and food cravings (especially for sweet, high-fat, and savory foods).
- Improved heart function: GLP-1 receptors are found in heart cells and blood vessels, which is why Orforglipron may help protect the heart, support better heart function, and lower blood pressure.
- Weight loss: By reducing appetite, cravings, and calorie intake, Orforglipron can support weight loss. On average, participants in a clinical trial lost between 8.6% and 12.6% of their body weight, or about 19.8 to 29.3 pounds, after 26 weeks of taking Orforglipron. In comparison, the placebo group lost only 2%, or about 4.6 pounds. After 36 weeks, the placebo group had lost an average of 2.3%, or 5.3 pounds, while those on Orforglipron lost between 9.4% and 14.7%, or 21.6 to 34 pounds.
What are the potential uses of Orforglipron?
Orforglipron is currently being tested in clinical trials to see if it can help treat type 2 diabetes and obesity, with promising early results.
Since Orforglipron mimics the natural hormone GLP-1, which is found in organs like the kidney, liver, and heart, it’s also believed to offer benefits for other health conditions. These may include chronic kidney disease, non-alcoholic fatty liver disease, and heart disease.
Another GLP-1 receptor agonist, Wegovy, has already been approved by regulators like Health Canada and the U.S. FDA to reduce the risk of cardiovascular problems like strokes, heart attacks, and cardiovascular death in people with cardiovascular disease alongside overweight or obesity. So Orforglipron may have a similar potential for improving heart health.
However, Orforglipron hasn’t been approved for any of these conditions yet. Clinical trials are still underway to prove its safety and effectiveness.
What does the current research say?
Results from clinical studies show that Orforglipron (LY3502970) may help with both blood sugar control and weight loss.
In clinical trials, people with obesity who took Orforglipron saw significant weight loss. Over 36 weeks, those on a 12mg dose lost an average of 9.4% of their body weight or 21.6 pounds, while those on a 45mg dose lost 14.7% or 34 pounds. In comparison, the placebo group only lost 2.3% or 5.3 pounds. Between 46% and 75% of people taking Orforglipron (compared to just 9% in the placebo group) lost at least 10% of their body weight.
For people with type 2 diabetes, Orforglipron also showed very good results in lowering blood sugar. A phase 2 study found that it reduced HbA1c levels—an important measure of long-term blood sugar control—by up to 2.10%. This was better than dulaglutide (Trulicity), which lowered HbA1c by 1.10%, and much higher than the placebo group, which only saw a 0.43% drop.
Like other GLP-1 receptor agonists, Orforglipron is also believed to have potential benefits beyond blood sugar control and weight loss. Researchers think it may help with kidney, liver, and heart disease, though more studies are needed to confirm these effects.
What are the advantages of Orforglipron compared to other GLP-1 medications?
Orforglipron has some advantages compared to other GLP-1 agonists. Unlike Wegovy or Zepbound, which are injectable peptides, Orforglipron is a small, non-peptide molecule. This means it can be made into a pill that you can take by mouth, which is more convenient for some people than injectable medications.
Because it’s smaller and simpler to make, Orforglipron pills will also likely be cheaper to produce, store, and package. This could make it more affordable and easier to access, as it wouldn’t face the same supply shortages that sometimes affect injectable treatments.
Orforglipron is also less likely to become less effective over time, so you might not develop resistance as quickly as with other GLP-1 agonists. This is because it has a greater effect on a process called cAMP signaling (which regulates functions like metabolism and hormone release) and less effect on β-arrestin recruitment (which helps turn off cell receptors once they’ve been activated).
What’s more, clinical trials suggest that Orforglipron may be even more effective than GLP-1 injections like Wegovy or Zepbound for weight loss.
Will Orforglipron work better than Wegovy and Zepbound?
Early data suggests that Orforglipron could be more effective than semaglutide (Wegovy) and tirzepatide (Zepbound and Mounjaro). Zepbound is the version of tirzepatide specifically approved for weight loss and is authorized for sale in Canada.
Here’s how the highest doses of these weight loss medications compared in clinical trials:
- Orforglipron 45mg: 14.7% weight loss over 36 weeks.
- Wegovy (semaglutide) 2.4mg: 14.9% weight loss at week 68.
- Zepbound (tirzepatide) 15mg: 20.9% weight loss at week 72.
It’s difficult to directly compare these treatments, since the clinical trials had different conditions like BMI, population size, and treatment duration.
But it seems that Orforglipron 45mg was similarly effective to Wegovy 2.4mg in just over half the time. This suggests that Orforglipron might work faster than other GLP-1 agonists.
Since Orforglipron is a small molecule rather than a peptide-based medication like Wegovy and Zepbound, it’s absorbed more easily by the body. This allows more of the drug to reach the bloodstream and work effectively.
Orforglipron also affects key processes that regulate hormone levels and receptor sensitivity, like cAMP signaling and β-arrestin recruitment. Because of this, you may be less likely to develop resistance to the medication over time than you would with other GLP-1 agonists.
So although there hasn’t been a direct study comparing it to other GLP-1 agonists for weight loss, early results suggest that Orforglipron could be just as or even more effective than Wegovy and Zepbound.
What are the potential side effects of Orforglipron?
Like all medications, Orforglipron can have potential side effects. Similar to other GLP-1 medications, the most common side effects in clinical trials were gastrointestinal issues, such as nausea, vomiting, constipation, diarrhea, and acid reflux.
These side effects are dose-dependent, meaning they become more intense at higher doses. And they usually get better over time, as your body adjusts to the medication.
More clinical trials are currently underway with a larger group of people to look into any possible serious side effects.
When will Orforglipron be approved?
Orforglipron, which is being developed by Eli Lilly (the same company behind Zepbound and Mounjaro), is still undergoing late-stage clinical trials for treating type 2 diabetes and obesity, but the results aren’t out yet. Eli Lilly plans to share these results by the end of 2025.
After that, Eli Lilly will submit the results to the U.S. Food and Drug Administration (FDA), with submissions to other regulatory bodies like Health Canada expected to follow. The company is projecting that Orforglipron could be approved by late 2026.
What does this mean for the future of GLP-1 medications?
The future of GLP-1 medications is looking more convenient and accessible. As scientists continue to improve how often and how these medications are taken, we can expect them to become easier to use, with fewer side effects and a lower price tag.
Right now, most GLP-1s require daily or weekly doses. But in the coming years we could see options that only need to be taken once a month or even less, making it even easier for people to manage conditions like type 2 diabetes and obesity.
What weight loss medications are available now?
Although Orforglipron hasn’t been approved yet, there are other medications currently available for weight loss. Here are some examples:
- Wegovy (semaglutide): A weekly GLP-1 injection that helps regulate appetite and reduce calorie intake.
- Zepbound (tirzepatide): A weekly injection that targets both GLP-1 and GIP receptors to help control cravings and manage calorie intake.
- Saxenda (liraglutide): A daily GLP-1 injection that helps you feel fuller and regulate appetite.
- Orlistat (brand names Xenical and Alli): A pill taken three times a day with your meals that reduces fat absorption.
- Contrave (Bupropion and Naltrexone): A daily pill that affects brain receptors to help control appetite.
But no matter which treatment option you choose, these medications work best when combined with a balanced diet and regular physical activity.
Most of these medications, except for Alli, need a prescription. In most cases, you’ll qualify to get a prescription from your doctor if you have a BMI of 30 or higher or a BMI of 27 or higher with weight-related health issues like type 2 diabetes or cardiovascular disease.
Reference Popover #ref1
Treated trusted source
Wharton, S., et al. (2023).
Daily Oral GLP-1 Receptor Agonist Orforglipron for Adults with Obesity. The New England Journal of Medicine, 389(10).
Reference Popover #ref2
Treated trusted source
Zheng, Z., et al. (2024).
Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduction and Targeted Therapy, 9(1), pp.1–29.
Reference Popover #ref3
Treated trusted source
Ferhatbegović, L. Mršić, D. and Macić-Džanković, A. (2023).
The benefits of GLP1 receptors in cardiovascular diseases. Frontiers in clinical diabetes and healthcare, 8(4): 1293926.
Reference Popover #ref4
Treated trusted source
Frias, J.P., et al. (2023).
Efficacy and safety of oral orforglipron in patients with type 2 diabetes: a multicentre, randomised, dose-response, phase 2 study. 402(10400), pp. 472 - 483.
Reference Popover #ref5
Treated trusted source
von Scholten, et al. (2022).
The potential of GLP-1 receptor agonists in type 2 diabetes and chronic kidney disease: from randomised trials to clinical practice. Therapeutic Advances in Endocrinology and Metabolism, 13, p.20420188221112490.
Reference Popover #ref6
Treated trusted source
Mantovani, A., et al. (2021).
Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Metabolites, 11(2), p.73.
Reference Popover #ref7
Treated trusted source
FDA (2024).
FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight. FDA.
Reference Popover #ref8
Treated trusted source
Wilding, J.P.H., Batterham, R.L. and Calanna, S. (2021).
Once-Weekly Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 384(11), pp.989–1002.
Reference Popover #ref9
Treated trusted source
Jastreboff, A.M., et al. (2022).
Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387(3).
Reference Popover #ref10
Treated trusted source
Dutta, D., et al. (2024).
Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis. Obesity science & practice, 10(2).
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