Orforglipron: what to know about this new oral GLP-1 for weight loss

Weight loss medications are a-plenty. But weight loss pills that offer benefits similar to injectable GLP-1 drugs? They may be hitting the market soon, with one promising option called orforglipron (pronounced or-FOR-glip-ron).

Orforglipron is an oral GLP-1 medication for weight loss and diabetes that’s in the final stages of development by Eli Lilly. (Yes, the same company that makes slim-down superstar, Zepbound.) While it’s not yet approved by the US Food and Drug Administration (FDA), the pill may be soon enough. 

So, there’s no better time than the present to get to know orforglipron, how it works, its potential side effects, and more. 

Orforglipron is a new oral medication for weight loss and type 2 diabetes that’s being developed by Eli Lilly. 

Key details to know about this next-gen GLP-1 receptor agonist:

• It’s a once-daily pill that doesn’t require any fasting. The current GLP-1 pill option, oral semaglutide or Rybelsus, must be taken on an empty stomach with a small amount of water, followed by a 30-minute wait before any other pills, food, or drinks. (FYI, Rybelsus is approved for type 2 diabetes, not weight loss.)

• Orforglipron is not a peptide. Most GLP-1 medications are peptides that are easily damaged by digestive enzymes and poorly absorbed in the gut. As such, the injection route works better for current GLP-1 drugs. Orforglipron is a non-peptide. Its molecular structure allows it to stay more stable and better absorbed through the gut.  

• Results from Lilly’s studies have shown that orforglipron can lead to major improvements in both blood sugar and weight. Research thus far has been done in adults with type 2 diabetes whose blood sugar remains high despite lifestyle changes and adults with obesity or overweight who do not have diabetes 

• The brand name isn’t known yet. If approved by the FDA, Lilly will announce the brand name (which hopefully will be easier to say and spell!) and dosage details. It may also have separate versions for diabetes vs. weight loss, similar to semaglutide (Ozempic vs. Wegovy).

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Ro members taking branded GLP-1 medications were paid for their testimonials.

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The orforglipron pill generally works the same way as other GLP-1 medications, such as semaglutide. These drugs mimic a natural gut hormone called glucagon-like peptide-1 (GLP-1) to help regulate blood sugar levels, digestion, and appetite. 

When orforglipron attaches to GLP-1 receptors, it:

• Increases insulin secretion to keep blood sugar steady.

• Slows stomach emptying so food stays in your stomach longer, helping you feel full sooner and longer after eating. 

• Reduces appetite so you feel less hungry and consume fewer calories to support weight loss.

Clinical studies suggest that orforglipron can significantly improve both weight loss and blood sugar control in adults with obesity or type 2 diabetes. 

Weight loss: 

• In a Phase 2 clinical trial, adults with overweight or obesity lost an average of 9.4%--14.7% of their starting weight after 36 weeks of taking orforglipron. Those who took a placebo lost just 2.3% of their body weight.  

• In a Phase 3 ATTAIN-1 trial, adults who took orforglipron for 72 weeks lost an average of 7.5%--11.2%. The placebo group had merely a 2% average weight loss.

Type 2 diabetes:

• In the Phase 3 ACHIEVE-1 trial, adults with “early” type 2 diabetes who took orforglipron experienced a drop in their A1C from 8% to 6.5%–6.7% after 40 weeks. (FYI, participants were not on any other diabetes medications at the start of the trial.)

• Participants also had an average weight loss of 4.5%–7.6% over the same period, with those who took higher doses experiencing the higher end of the range of weight loss. 

Common orforglipron side effects reported in trials are similar to other GLP-1 drugs and mainly affect the digestive system:

• Nausea

• Constipation

• Vomiting

• Diarrhea

• Burping (eructation)

• Indigestion (dyspepsia)

As with other GLP-1s, more serious side effects are possible, such as an inflamed pancreas or low blood sugar (hypoglycemia). Lilly plans to release additional safety data in early 2026. And once the medication is FDA-approved, there will be more complete information about adverse effects on the drug label.

Interaction information at this point is limited. But it’s likely that other medications or supplements could affect how orforglipron works or may raise the risk of side effects. For example, if you take other diabetes medications — like insulin or pills that lower blood sugar — your healthcare provider may need to adjust your doses if you start orforglipron. 

Because orforglipron is still being studied, its official contraindications have not yet been confirmed. However, as with other GLP-1 medications, it will likely not be recommended for people with a personal or family history of thyroid tumors or multiple endocrine neoplasia type 2 (MEN2). 

Additionally, there’s not enough data to determine whether orforglipron is safe during pregnancy or breastfeeding. People planning to become pregnant will probably be advised to stop orforglipron several weeks before conception — once official guidance becomes available.

Orforglipron may be available sometime in 2026. 

Lilly plans to submit its new drug application for orforglipron to the FDA in two phases: first for obesity in late 2025, then for type 2 diabetes sometime in 2026. 

Once the FDA accepts a new drug application, the standard review process typically takes up to 10 months. That means, if everything stays on track, orforglipron could be available by mid-to-late 2026.

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So, how does orforglipron compare to other injectable weight loss medications, such as fellow GLP-1s semaglutide (Wegovy) and dual GLP-1/GIP medications like tirzepatide (Zepbound)? 

First, quick refresher on orforglipron:

• It is not (yet) FDA approved. 

• It’s an oral GLP-1 receptor agonist in late-stage development for obesity and type 2 diabetes. 

• It activates GLP-1 receptors to lower blood sugar levels, slow how fast food moves through the digestive system, and curb appetite. 

• It doesn’t have an official dose or dosage yet, but it was taken once daily in clinical trials. 

In comparison:

• Semaglutide is a once-weekly injection that’s FDA-approved for weight loss under the brand name Wegovy. It’s a GLP-1 like orforglipron. 

• Tirzepatide is a once-weekly injection that’s FDA-approved for weight loss and chronic weight management under the brand name Zepbound.  It’s a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1.

How do average weight loss results compare? While real-life experience can vary, here’s what clinical trial results have found:

• Orforglipron: Phase 3 obesity trials in people without diabetes show up to 11% weight loss after 72 weeks when taking 36 mg daily (the highest dosage option).

• Semaglutide (Wegovy): STEP studies found 15% average weight loss after 68 weeks in adults with obesity or overweight (without diabetes) with a weight-related health condition.

• Tirzepatide (Zepbound): SURMOUNT-1/--2 trials show 15%–22% average weight loss at 72 weeks, depending on dose and whether participants had diabetes.

Keep in mind that the best way to compare medications is a head-to-head clinical trial. That’s because different trial results can vary significantly depending on the participants, the study design, the study duration, and the outcomes measured. 

Orforglipron is a next-generation oral GLP-1 that could help many people reach and maintain their health goals, particularly in terms of weight and blood sugar. Here’s a recap of what we’ve covered:

• Orforglipron is an oral GLP-1 medication made by Eli Lilly that’s still undergoing clinical trials. 

• It is not (yet) approved by the FDA, so it does not have a brand name at the moment

• There’s also no official dosage yet. In studies, people took orforglipron as an oral capsule once daily in the morning. 

• Research thus far shows strong benefits for weight loss and blood sugar control — similar to injectable GLP-1s, such as semaglutide and tirzepatide. 

• If all goes well, Lilly plans to submit for FDA approval in late 2025 and early 2026.