Orforglipron vs. Tirzepatide: 6 Ways These Weight-Loss Medications Compare

There has been a lot of research recently into new weight-loss medications. This has led to the FDA approval of products such as tirzepatide (Mounjaro, Zepbound) and orforglipron (Foundayo).

But when there are multiple medications available that have similar uses, it’s common to wonder how they compare. So how is orforglipron different from tirzepatide?

Orforglipron vs. tirzepatide at a glance

To compare medications, it helps to have all the details about them side by side. The table below highlights the main similarities and differences between orforglipron and tirzepatide.

Below are six things to keep in mind when comparing orforglipron versus tirzepatide.

1. Orforglipron and tirzepatide have different FDA-approved uses

One of the biggest differences between orforglipron and tirzepatide is what they’re FDA approved to treat. Orforglipron is approved for weight loss among adults who are considered obese. It’s also approved for weight loss among adults considered overweight who also have at least one weight-related health condition, such as high cholesterol or high blood pressure.

Tirzepatide is approved as two brand-name medications:

• Mounjaro for Type 2 diabetes among people ages 10 and older

• Zepbound for weight loss and obstructive sleep apnea (OSA) among adults considered obese. It’s also approved for weight loss for adults considered overweight who also have at least one weight-related health condition.

2. Orforglipron and tirzepatide work in slightly different ways

Another difference between orforglipron and tirzepatide is how they work. Both medications act like the gut hormone GLP-1. But tirzepatide also acts like a second gut hormone: GIP.

Despite this slight difference, both orforglipron and tirzepatide have the following effects in the body:

• Signaling the pancreas to release insulin when you eat

• Reducing the amount of new glucose (sugar) your liver makes

• Slowing the passage of food through your digestive tract, helping you feel fuller longer

• Targeting areas of your brain that help regulate appetite and food cravings

• Counteracting certain hunger hormones that affect weight gain

Tirzepatide may also help reduce inflammation that contributes to OSA. It’s unknown whether orforglipron has this effect.

3. Orforglipron is a once-daily pill, and tirzepatide is a once-weekly injection

Dosage forms are another difference to consider. Orforglipron is a pill, and tirzepatide is an injection.

Orforglipron is an oral pill that you take once a day. Unlike other GLP-1 pills, such as Wegovy (semaglutide), you don’t need to time your dose around meals. You can take orforglipron with or without food, at any time of day. But make sure to take it around the same time every day.

Tirzepatide is an injection that you give to yourself once a week. It comes as both single-use and multi-use injector pens and single-use vials. You can inject tirzepatide with or without food at any time of day. But you should inject your dose on the same day each week.

4. Orforglipron and tirzepatide both work well for weight loss

Orforglipron and tirzepatide both lead to significant weight loss.

Tirzepatide is one of the most effective weight-loss medications available. People using tirzepatide in clinical trials lost an average of 15% to 21% of their starting body weight over 72 weeks (about 16.5 months).

Orforglipron also works well for weight loss. People in clinical trials lost an average of 7% to 11% after 72 weeks (16.5 months). It’s one of the more effective oral weight-loss medications.

Orforglipron may also be helpful for people switching from an injectable GLP-1 medication to an oral version. Studies found that people using either Zepbound or Wegovy were able to maintain the weight they lost after switching to orforglipron.

5. Orforglipron and tirzepatide have similar common side effects

Because orforglipron and tirzepatide act like GLP-1, they share many common side effects. These mainly affect the digestive tract and include:

• Diarrhea

• Nausea

• Upset stomach

• Constipation

• Vomiting

• Burping

• Stomach pain

Orforglipron’s and tirzepatide’s labels also contain warnings for rare but serious side effects and risks. These include:

• Gallbladder problems, including gallstones

• Reports of pancreatitis (swelling of the pancreas)

• Kidney damage if vomiting or diarrhea is severe

• Severe gastrointestinal complications, such as gastroparesis (delayed stomach emptying)

• Hypoglycemia (low blood sugar)

• Allergic reactions

Orforglipron and tirzepatide also have a boxed warning (the FDA’s strictest warning for medications) for thyroid C-cell tumors. These tumors were seen in animal studies of the medication. This risk hasn’t been confirmed in human studies. But to be safe, you shouldn’t use tirzepatide if you have a personal or family history of medullary thyroid cancer. You also shouldn’t use it if you have multiple endocrine neoplasia syndrome type 2 (MEN 2).

6. Orforglipron and tirzepatide have different interactions

Orforglipron and tirzepatide have a low risk of causing low blood sugar. But if you also take certain diabetes medications, such as insulin, you’re more likely to experience this side effect.

Beyond this, other drug interactions vary with orforglipron and tirzepatide. It’s a good idea to share a complete medication list with your prescriber and pharmacist before starting either orforglipron or tirzepatide. Be sure to include both prescription and over-the-counter medications, as well as vitamins and supplements, on this list.

Can you take orforglipron and tirzepatide together?

No, you shouldn’t take orforglipron and tirzepatide together. Both medications work in somewhat similar ways and have the same side effects. Combining them can raise your risk for or worsen existing side effects.

If orforglipron or tirzepatide isn’t working well enough on its own, talk to your prescriber. They can work with you to develop a plan that works for your needs.

How to save on Mounjaro, Zepbound, and Foundayo

There are ways to save on Mounjaro, Zepbound, and Foundayo, which are available as brand-name medications. All three have copay savings programs available from the manufacturer. If you have commercial insurance, you may be eligible to pay as little as $25 per prescription for Mounjaro, Zepbound, or Foundayo.

If your plan doesn’t cover Zepbound, you may still be able to save with the copay card, but prices vary by formulation. You can access Zepbound KwikPen through GoodRx starting at $299 per month. You can also access Foundayo through GoodRx starting at $149 per month. Subscribers to GoodRx for Weight Loss can access FDA-approved, brand-name GLP-1 medications like Zepbound and Foundayo.

Lower-cost single-dose Zepbound vials and KwikPens are available through LillyDirect for $299 (2.5 mg), $399 (5 mg), and $449 (7.5 mg, 10 mg, 12.5 mg, and 15 mg) per month. Foundayo is also available through LillyDirect for $149 (0.8 mg), $199 (2.5 mg), and $299 (5.5 mg, 9 mg, 14.5 mg, and 17.2 mg).

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Written by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

Alyssa Billingsley, PharmD

Alyssa Billingsley, PharmD, is the director of pharmacy content for GoodRx. She has over a decade of experience as a pharmacist and has worked in clinical, academic, and administrative roles.

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