Is Zepbound a GLP-1? How its dual-action approach works

If you’ve been wondering whether Zepbound is a GLP-1, the short answer is yes, but it actually acts on receptors for two gut hormones. Its active ingredient, tirzepatide, targets GLP-1 receptors, as do several other weight-management medications, like Wegovy. The second hormone Zepbound acts on is glucose-dependent insulinotropic polypeptide (GIP).

This means the official prescribing label lists Zepbound as both a GIP and GLP-1 receptor agonist. It’s that extra hormone that may help explain the weight loss results people experienced in trials.

Here’s how each hormone works, how Zepbound compares with similar drugs, and which ones it shouldn’t be used with.

Zepbound is a GLP-1 medication because its active ingredient, tirzepatide, switches on GLP-1 receptors. But tirzepatide also acts on GIP receptors, which puts Zepbound in a different group from GLP-1-only drugs like Wegovy.

Through GIP and GLP-1 receptors, tirzepatide can help lower how many calories people eat, most likely by curbing appetite.

Wegovy takes a single-target approach. Its active ingredient, semaglutide, closely matches human GLP-1 and works on the GLP-1 receptor alone.

Zepbound does share its active ingredient with another prescription medication. Mounjaroalso contains tirzepatide, but the two brands are approved for different uses. 

• Mounjaro treats type 2 diabetes and can lower heart attack and stroke risk and even death in adults with type 2 diabetes who are at high risk of these events.  

• Zepbound is approved for weight management and moderate to severe obstructive sleep apnea in certain adults. 

Because Zepbound and Mounjaro contain the same active ingredient, there’s no need to take these medications together.

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GLP-1 is a hormone your gut releases after you eat. One of its main jobs is helping your pancreas make more insulin when blood sugar rises, which helps bring blood sugar back down after a meal.

GLP-1 medications act on the same receptor as natural GLP-1, but at much higher levels than your body makes on its own. They slow how fast food leaves your stomach, an effect that’s strongest early in treatment, and they can also act on brain areas that control hunger. Together, these effects can help you feel less hungry and eat less.

Tirzepatide slows stomach emptying too, especially after the first doses, so Zepbound shares this GLP-1 effect with other medications in its drug class.

GIP is a gut hormone whose main job is helping your body release more insulin after meals. In healthy people, it does more of this work than GLP-1 does.

GIP has receptors in fat tissue, where it may help control how your body stores and breaks down fat, while GLP-1 receptors there are largely absent.

GIP’s role in appetite is still being studied. Receptors for both GIP and GLP-1 sit in parts of the brain linked to appetite, and adding GIP to GLP-1may curb food intake even more, though this has been seen in animal studies and hasn't been confirmed in people. Unlike GLP-1, GIP doesn’t slow stomach emptying. 

Tirzepatide can switch on both receptors because it’s a modified version of the natural GIP hormone, engineered to alsowork on GLP-1 receptors.

Another change, a fatty acid chain, helps tirzepatide latch onto albumin, a protein in your blood. As a result, tirzepatide has a half-life of about 5 days, meaning your body takes that long to clear half a dose. This slow clearance supports once-weekly dosing, which is why Zepbound is a weekly injection.

Tirzepatide doesn’t work on both receptors equally. In studies, it appears to act on GIP receptors more than GLP-1 receptors, and it behaves much like natural GIP at the GIP receptor. This imbalance, along with differences in how it acts at the GLP-1 receptor, may help explain how well tirzepatide works, though its exact role is still being studied.

Zepbound shares its dual GIP and GLP-1 action with Mounjaro, which contains the same active ingredient. Wegovy, Ozempic, Saxenda, and Foundayo work on GLP-1 receptors alone.

These medications also differ in how they’re taken and whether the US Food and Drug Administration (FDA) has approved them for weight management.

*These results come from separate trials with different designs, so they aren’t a direct head-to-head comparison. People with type 2 diabetes tend to lose less weight on these medications. Mounjaro and Ozempic labels only report weight change from type 2 diabetes trials.

Ozempic contains the same active ingredient as Wegovy and comes as both a weekly shot and a daily pill. Both forms are approved for adults with type 2 diabetes, but not for weight management. Wegovy also comes in higher maximum doses, which is another way the two differ.

How a medication is taken may also help narrow your options. Zepbound and Wegovy injections are both once-weekly shots, while Saxenda is taken as a daily shot.

If you’d prefer oral medication, the Wegovy pill and Foundayo are daily tablets approved for weight management. Both act on GLP-1 receptors alone, so neither includes the GIP action found in Zepbound. The Wegovy pill needs to be taken on an empty stomach with a small sip of water, at least 30 minutes before eating; Foundayo can be taken with or without food. 

Two large trials help put numbers on tirzepatide’s results: SURMOUNT-1, which compared it with a placebo, and SURMOUNT-5, which compared it head-to-head with semaglutide, the active ingredient in Wegovy. Tirzepatide led to more average weight loss than semaglutide, and its added GIP action may be part of the reason.

In the72-week SURMOUNT-1 trial, 2,539 adults with obesity, or with overweight plus a weight-related health problem, took tirzepatide or a placebo. None of them had diabetes. People on tirzepatide lost 15%-20.9% of their body weight on average, depending on the dose, while people on the placebo lost 3.1%.

Most people on tirzepatide lost at least 5% of their body weight (85%-91%, depending on the dose), compared with 35% of people on the placebo.

SURMOUNT-1 didn’t include a GLP-1-only drug, which is where SURMOUNT-5 comes in. It enrolled 751 adults with obesity or with overweight and a weight-related health problem, who didn’t have type 2 diabetes. After 72 weeks, participants on tirzepatide lost 20.2% of their body weight on average, compared with 13.7% with semaglutide.

Semaglutide was given at up to 2.4 mg, the standard Wegovy maintenance dose at the time. Wegovy has since been approved at a higher 7.2 mg dose, which hasn’t been tested head-to-head against tirzepatide.

Waist size followed the same pattern. It shrank by an average of about 7.2 inches (18.4 cm) with tirzepatide and about 5.1 inches (13 cm) with semaglutide.

In both groups, the most common side effects were digestive, and most were mild to moderate and happened mainly while doses were being raised.

SURMOUNT-5 does have limits, though. It was open-label, meaning people knew which drug they were taking, and Eli Lilly, the company that makes Zepbound, paid for it. And because tirzepatide and semaglutide are different molecules, not the same drug with and without GIP, the trial can’t show how much of the difference comes from GIP.

Weight loss results are one of several factors to talk through with your healthcare provider as you compare the two drugs.

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Because Zepbound acts on GLP-1 receptors, it shouldn’t be taken with any other GLP-1 drug or any other product that contains tirzepatide. That means you shouldn’t pair it with drugs such as Mounjaro, Wegovy, Ozempic, or Foundayo.

Zepbound also carries a boxed warning about a risk of thyroid C-cell tumors. Tirzepatide caused these tumors in rats, and it’s unknown whether it causes them in people, including a type of thyroid cancer called medullary thyroid carcinoma (MTC).

For that reason, Zepbound isn’t for people with a personal or family history of MTC. It’s also off-limits for anyone with an endocrine system condition called multiple endocrine neoplasia syndrome type 2 (MEN 2), or anyone who’s had a serious allergic reaction to tirzepatide or its ingredients. Tell your healthcare provider if you notice a lump in your neck, hoarseness, trouble swallowing, or shortness of breath.

The most common Zepbound side effects are stomach-related, like nausea, diarrhea, vomiting, and constipation. The first three mostly happen while your dose is being increased and tend to ease over time.

Because Zepbound slows how fast your stomach empties, it may makebirth control pills less effective. If you take them, your healthcare provider may suggest switching to a non-oral method or adding a barrier method like condoms for four weeks after you start Zepbound and after each dose increase. Zepbound isn’t recommended for use during pregnancy, so tell your healthcare provider if you are pregnant or planning to become pregnant.

Other Zepbound risks

Zepbound’s label lists other serious risks, including inflammation of the pancreas (pancreatitis), gallbladder problems, kidney problems caused by dehydration, severe allergic reactions, severe stomach problems, and temporary worsening of diabetes-related eye damage (diabetic retinopathy) in people with type 2 diabetes. It isn’t recommended for people with severe gastroparesis, a condition where the stomach empties very slowly.

Zepbound may also increase the chance of food or liquid getting into your lungs during surgery or procedures that use anesthesia or deep sedation. So tell your healthcare provider before any planned procedure since they may recommend you hold some of your doses before surgery.

Zepbound can lower blood sugar, and low blood sugar is more likely if you take it with insulin or certain other diabetes medications, so be sure to tell your healthcare provider about all medications you take.

Zepbound is a GLP-1 medication, and its second target, GIP, makes it a dual agonist. If you’re considering it against other GLP-1 meds, here are the key points to keep in mind:

• Zepbound works on two hormone receptors. Tirzepatide, the drug inside Zepbound, turns on receptors for both GLP-1 and GIP.

• Each hormone plays a different role. GLP-1 targets hunger and how fast your stomach empties, while GIP does more of the insulin work after meals in people without diabetes.

• Tirzepatide came out ahead in a direct comparison with another GLP-1. In a 72-week trial against semaglutide at up to 2.4 mg, it led to 6.5 percentage points more average weight loss.

• Zepbound has clear safety limits as outlined in its prescribing information. It isn’t recommended alongside other GLP-1 drugs or tirzepatide products, it carries a boxed warning about thyroid C-cell tumors, and it isn’t recommended for people with MEN 2 or a personal or family history of medullary thyroid carcinoma.

If you’re curious whether Zepbound or another GLP-1 medication could fit your goals, a Ro healthcare provider can review your health history and help you explore your options.