What Are GLP-1 Medications? How They Work and Which Ones Exist

GLP-1 (glucagon-like peptide-1) is a hormone your gut releases when you eat. It helps the pancreas release insulin when blood sugar rises, slows the passage of food from the stomach into the intestine and turns down appetite^[1,2]. The “GLP-1s” people talk about are medications that mimic this hormone or switch on its receptor. In the US, the FDA has approved semaglutide (Ozempic, Wegovy, Rybelsus), tirzepatide (Mounjaro, Zepbound), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, the first one, now discontinued) and orforglipron (Foundayo). Tirzepatide also acts on a second gut hormone, GIP.

I built this guide from two reviews of the hormone, by Müller and colleagues (2019) and Drucker (2018), each drug’s FDA label and approval record, the EU prescribing information and the trials I cite. Label facts have a dotted underline and the date I checked them. There are separate guides to semaglutide, tirzepatide and liraglutide.

The GLP-1 hormone: where it’s made and what it does

GLP-1 is made mainly by L cells in the lining of the gut, which are most abundant toward the end of the small intestine (the ileum) and in the colon. A small group of neurons in the brainstem makes it too, according to Müller’s review. L cells release it into the blood when nutrients reach the intestine^[1].

Once in circulation, GLP-1 does four main things, as Drucker summarizes^[2]:

• Raises insulin from the pancreas, but only when blood sugar is high. This is called a glucose-dependent effect.
• Lowers glucagon, the hormone that tells the liver to release glucose.
• Slows stomach emptying, so food stays in the stomach longer.
• Reduces food intake, partly by acting on appetite centers in the brain.

The result is that blood sugar rises less after meals and people eat less. GLP-1 is one of the incretins: gut hormones that explain why glucose taken by mouth triggers more insulin than the same glucose given into a vein^[1,2]. The other key incretin is GIP (glucose-dependent insulinotropic polypeptide), which comes back with tirzepatide.

Because the insulin effect depends on glucose, there’s a practical consequence. The US labels flag low blood sugar (hypoglycemia) mainly when these drugs are used with insulin or an insulin secretagogue, such as a sulfonylurea, another type of diabetes medication^[17]. In SURPASS-3 (trial summary), with 1,444 adults with type 2 diabetes taking metformin, alone or with an SGLT2 inhibitor, blood sugar below 54 mg/dL or severe hypoglycemia occurred in 1 to 2% on tirzepatide and 7% on insulin degludec over 52 weeks^[54].

From hormone to medication

The natural hormone is nearly useless as a drug because it doesn’t last. An enzyme in the blood and tissues, DPP-4, cuts it up almost immediately, and the kidneys clear the rest^[1]. Its half-life (the time it takes the body to clear half of it) is 1 to 2 minutes in Müller’s review^[1] and 1.5 to 2 minutes in the US Victoza label^[22].

The Gila monster

In 1992, Eng and colleagues isolated a peptide they called exendin-4 from the venom of the Gila monster (Heloderma suspectum), a venomous lizard^[3]. It resembles human GLP-1, sharing about 53% of its first 30 amino acids, and it activates the same receptor, according to Müller’s review^[1].

Its synthetic version, exenatide (Byetta), injected twice a day, was the first drug in this family^[1]. The FDA approved it on April 28, 2005^[4], and the EU authorized it on November 20, 2006, both for type 2 diabetes^[26]. Drugs@FDA now lists both Byetta pens as discontinued in the US^[4]; the EU still lists it as authorized^[26].

How the effect was stretched out

Since then, each generation has aimed to last longer, so people need fewer doses:

Source: each drug’s US label (linked), sections 11, 12.1 and 12.3^{[16,19,22,23,24,25]}.

That’s why semaglutide and liraglutide are called GLP-1 analogs: tweaked versions of the human hormone. According to their US labels, semaglutide shares 94% of its sequence with human GLP-1^[16], and liraglutide 97%^[22]. All of them are also GLP-1 receptor agonists: they bind to that receptor and switch it on, as the hormone does. Orforglipron activates the receptor without resembling the hormone. It’s a small molecule, not a peptide, and it’s taken by mouth^[24].

Which GLP-1 medications exist

The table covers the approved drugs and the two furthest along in development, checked against Drugs@FDA, the FDA labels and the European Medicines Agency (EMA). Years are each brand’s first approval in that region.

Sources: Drugs@FDA^{[4,5,6,7,8,9,10,11,12,13,14]} and the EU prescribing information (linked in the table)^{[26,27,28,29,30,31,32,33]}; the EMA’s list of applications under review^[34] (September 2026); announcements from Novo Nordisk^[50] and Eli Lilly^[51] for the drugs in development and Foundayo’s diabetes application.

A few details the table can’t hold:

• Ozempic tablets. In January 2026, the FDA approved a newer semaglutide tablet under the Rybelsus application, sold as Ozempic tablets^[9]. They share one label with Rybelsus, which warns that the two are not substitutable on a mg-to-mg basis^[18].
• Wegovy tablets. The daily pill, its trials and its side effects are covered in the Wegovy pill.
• Wegovy 7.2 mg. On March 19, 2026, the FDA approved a higher weekly dose, sold as Wegovy HD^[10]. The label reserves it for adults who tolerate 2.4 mg for at least 4 weeks and for whom additional weight reduction is clinically indicated^[16]. The EU prescribing information includes a 7.2 mg dose too^[28].
• Generics. The FDA approved the first generics of exenatide and Victoza in late 2024^[15], and Drugs@FDA lists generics of Saxenda too^[6].
• Orforglipron elsewhere. The UK’s medicines regulator (MHRA) authorized it on August 10, 2026, for weight management and type 2 diabetes^[35]. Its type 2 diabetes trials include ACHIEVE-1 (summary), against placebo^[66], and ATTAIN-2 (summary), focused on weight: −9.6% on 36 mg versus −2.5% on placebo at 72 weeks^[67].

GLP-1 receptor agonists, dual and triple agonists: how they differ

They all share the same base: they activate the GLP-1 receptor. What changes is whether they activate other receptors too.

GLP-1 receptor agonists (exenatide, liraglutide, dulaglutide, semaglutide, orforglipron). They act on that receptor only. This is the family with the longest track record.

Dual GIP/GLP-1 agonists (tirzepatide). They activate the GLP-1 receptor and the receptor for GIP, the other incretin. Both hormones stimulate insulin when blood sugar is high.

Triple GIP/GLP-1/glucagon agonists (retatrutide, in development). These add the glucagon receptor. That sounds contradictory, since glucagon raises blood sugar. The idea, according to Müller’s review, is to harness other effects of glucagon, such as higher energy expenditure and less liver fat, while GLP-1 offsets its effect on glucose^[1].

Amylin combinations (CagriSema, in development). This isn’t one molecule but two: semaglutide plus cagrilintide, an amylin analog. Amylin is another hormone, released by the pancreas along with insulin when you eat. It also helps regulate how much you eat, acting on appetite through the brain^[68].

Each of the drugs in development has its own guide: retatrutide, survodutide, CagriSema, amycretin and maridebart cafraglutide (MariTide).

What the trials show on weight

These are the main placebo-controlled trials for each type.

These are averages, with a lot of variation between people, and the rows can’t be compared with each other: population, length and design all differ. SCALE reports weight loss in kilograms, and the retatrutide trial is a small phase 2 study. People with type 2 diabetes lose less, as STEP 1 vs. STEP 2, SURMOUNT-1 vs. SURMOUNT-2 and REDEFINE 1 vs. REDEFINE 2 show. The manufacturers funded all of them: Novo Nordisk the SCALE, STEP, OASIS and REDEFINE trials, Eli Lilly the SURMOUNT trials, ATTAIN-1 and the retatrutide trial^{[36,37,38,41,42,45,46,47,55,56,57]}. Retatrutide’s first phase 3 obesity results were published on September 29, 2026, and I haven’t added them to the table yet. In TRIUMPH-1, with 2,339 adults with obesity and without diabetes, weight fell by 17.6% to 25.0% depending on the dose over 80 weeks, vs. 3.9% on placebo^[69]. In TRIUMPH-2, with 1,152 adults with obesity and type 2 diabetes, it fell by 11.9% to 18.8%, vs. 5.1%^[70]. Eli Lilly funded both^[69,70]. An earlier phase 3 trial, TRANSCEND-T2D-1 (trial summary), was in type 2 diabetes^[48]. Each of these trials, and more, has a plain-language summary in our studies section.

Head-to-head: tirzepatide vs. semaglutide

Two published trials have compared them directly:

• SURMOUNT-5 (trial summary), in 751 adults with obesity or overweight without diabetes, over 72 weeks. Weight fell 20.2% on tirzepatide and 13.7% on semaglutide, each at the maximum tolerated dose: a difference of 6.5 percentage points. It was open-label (participants knew which drug they got) and funded by Eli Lilly, which makes tirzepatide^[43].
• SURPASS-2 (trial summary), in 1,879 adults with type 2 diabetes taking metformin, over 40 weeks. HbA1c (average blood sugar over the past few months) fell 2.01 to 2.30 points on tirzepatide vs. 1.86 on semaglutide 1 mg. Tirzepatide also took off 1.9 to 5.5 kg (4 to 12 lb) more^[44]. The comparison was against semaglutide 1 mg, not the higher doses approved later.

Other head-to-head trials compare other drugs in the family. In STEP 8 (trial summary), with 338 adults without diabetes, weight changed by −15.8% on semaglutide 2.4 mg weekly and −6.4% on liraglutide 3.0 mg daily at 68 weeks^[58]. In ACHIEVE-3 (trial summary), with 1,698 adults with type 2 diabetes taking metformin, HbA1c fell 1.91 points on orforglipron 36 mg and 1.47 on oral semaglutide 14 mg at 52 weeks, with more digestive side effects on orforglipron^[59].

Without a trial that compares two drugs directly, any “this one beats that one” claim mixes studies that can’t be compared.

Brands that share an active ingredient, and the two weekly weight-management shots, are compared in Ozempic vs. Wegovy, Mounjaro vs. Zepbound and Zepbound vs. Wegovy.

What they’re approved for

A drug is approved only for what its label says. Here’s the picture by use, US first:

Sources: section 1 of the US labels for Wegovy, Ozempic, Rybelsus and Ozempic tablets, Mounjaro, Zepbound, Saxenda, Victoza, Trulicity, Foundayo and Byetta^{[16,17,18,19,20,21,22,23,24,25]}; sections 4.1 and 5.1 of the EU prescribing information linked above^{[26,27,28,29,30,31,32,33]}.

Who the weight-management labels cover. The US labels name adults with obesity, or adults with overweight and at least one weight-related condition, always alongside a reduced-calorie diet and more physical activity^{[16,20,21,24]}. The EU labels spell out the numbers: a body mass index (BMI) of 30 or more, or 27 to 30 with at least one weight-related condition, such as high blood pressure or prediabetes^[28,30,32]. What BMI captures and what it misses is in what BMI measures.

Heart risk. In the SELECT trial, 17,604 adults aged 45 or older with existing cardiovascular disease, a BMI of 27 or more and no diabetes were followed for an average of 39.8 months. Heart attack, stroke or cardiovascular death occurred in 6.5% on semaglutide 2.4 mg and 8.0% on placebo^[40]. Based on this, the US Wegovy label includes reducing the risk of major adverse cardiovascular events in adults with established cardiovascular disease and either obesity or overweight^[16].

In type 2 diabetes, two trials measured the same kind of events. In SUSTAIN-6 (trial summary), with 3,297 adults with type 2 diabetes and high cardiovascular risk, a major cardiovascular event occurred in 6.6% on semaglutide and 8.9% on placebo over a median of 2.1 years^[60]. In SURPASS-CVOT (trial summary), with 13,299 adults with type 2 diabetes and atherosclerotic cardiovascular disease, it occurred in 12.2% on tirzepatide and 13.1% on dulaglutide over a median of 4.0 years: tirzepatide was noninferior, but it wasn’t shown to be superior^[61].

Kidney disease. In the FLOW trial (trial summary), with 3,533 people with type 2 diabetes and chronic kidney disease, semaglutide 1 mg weekly lowered the risk of the primary outcome, a combination of kidney failure, a drop of at least 50% in glomerular filtration rate and death from kidney or cardiovascular causes, by 24% versus placebo (hazard ratio 0.76), over a median follow-up of 3.4 years^[62].

MASH. Wegovy’s liver indication covers MASH without cirrhosis and with moderate to advanced fibrosis (stages F2 to F3) in adults. It’s an accelerated approval: it may depend on a confirmatory trial showing clinical benefit^[16]. It rests on the planned 72-week interim analysis of the ESSENCE trial (trial summary), in 800 patients with MASH and stage 2 or 3 fibrosis: steatohepatitis resolved without worsening of fibrosis in 62.9% on semaglutide 2.4 mg and 34.3% on placebo^[63].

Sleep apnea. The trial behind Zepbound’s sleep apnea approval, and where things stand outside the US, are in Zepbound for sleep apnea.

Everything else is off-label use or research. For example, in a phase 2 trial (trial summary) of 48 adults with alcohol use disorder, 9 weeks of semaglutide reduced cravings^[49]. That’s early evidence, not an approved use. There are also trials in heart failure with preserved ejection fraction and obesity. In STEP-HFpEF (trial summary), with 529 adults without diabetes, the KCCQ-CSS symptom and physical limitation score improved by 16.6 points on semaglutide 2.4 mg and 8.7 on placebo over 52 weeks^[64]. In SUMMIT (trial summary), with 731 adults, cardiovascular death or worsening heart failure occurred in 9.9% on tirzepatide and 15.3% on placebo over a median follow-up of 104 weeks^[65].

How they’re taken

There are three ways:

• Weekly injection under the skin: Ozempic, Wegovy, Mounjaro, Zepbound and Trulicity.
• Daily injection: Victoza, Saxenda and generic liraglutide.
• Daily tablet: Rybelsus, Ozempic tablets and Wegovy tablets, which are semaglutide, and Foundayo, which is orforglipron.

Semaglutide tablets come with specific instructions, because they affect how much drug is absorbed. According to the US labels for Wegovy and Rybelsus and Ozempic tablets, they’re taken once a day on an empty stomach in the morning, swallowed whole with up to 4 ounces of water and no other liquid, followed by a wait of at least 30 minutes before eating, drinking or taking other oral medications^[16,18]. The EU Rybelsus label adds a recommended fast of at least 8 hours beforehand^[29]. Orforglipron doesn’t have these restrictions: the Foundayo label says it’s taken once daily, with or without food^[24].

Almost every label starts with a low dose that’s stepped up over weeks or months. The Wegovy, Zepbound and Foundayo labels give the reason: to reduce the risk of gastrointestinal adverse reactions^[16,20,24]. Which drug, which dose and how fast to step up depends on your medical history, and your prescriber decides the schedule. That’s why this guide doesn’t give one.

Side effects, in brief

The most common side effects across the family are digestive. On Wegovy 2.4 mg, the US label reports nausea in 44% vs. 16% on placebo, and diarrhea in 30% vs. 16%^[16]. On Zepbound, nausea in 25% to 29% depending on the dose vs. 8% on placebo, and diarrhea in 19% to 23% vs. 8%^[20]. I cover food strategies in GLP-1 nausea and what to eat and constipation on GLP-1 medications.

Every US label in this guide except Byetta’s^[25] carries a boxed warning about thyroid C-cell tumors^{[16,17,18,19,20,21,22,23,24]}. For Wegovy, it says that in rodents, semaglutide caused thyroid C-cell tumors; it’s unknown whether it does in humans, and it’s contraindicated (must not be used) in people with a personal or family history of medullary thyroid carcinoma or with MEN 2^[16], a rare inherited condition. The other labels give the same warning for their own drug^{[17,18,19,20,21,22,23]}, except Foundayo’s: orforglipron isn’t active in rats or mice and didn’t cause tumors in them, but the label keeps the same contraindication because the human relevance of these rodent tumors with GLP-1 drugs hasn’t been determined^[24]. The full contraindications and warnings are in the label section of the guides to semaglutide, tirzepatide and liraglutide. For changes to the face, skin and hair that come with large weight loss, see Ozempic face and hair loss on GLP-1 medications.

What GLP-1 medications are not

They’re not fat burners. The US Wegovy label says that semaglutide decreases calorie intake, and the effect is likely mediated by appetite^[16]. People lose weight because they eat less. With less food, it gets harder to eat enough protein and keep muscle. I explain how in protein and muscle on GLP-1 medications, and you can estimate your target with the protein calculator.

They’re not for everyone. Each label defines who the drug is for and who shouldn’t use it. In the US, Ozempic, Rybelsus, Mounjaro, Victoza and Trulicity are approved only for uses tied to type 2 diabetes^{[17,18,19,22,23]}.

Compounded versions are not FDA-approved. The FDA explains that it doesn’t review compounded drugs for safety, effectiveness or quality before they’re sold. As of May 31, 2026, it had received 990 adverse event reports for compounded semaglutide and more than 730 for compounded tirzepatide, some linked to dosing errors and some requiring hospitalization. It considers them likely underreported, since state-licensed pharmacies that aren’t outsourcing facilities don’t have to report them. Retatrutide and cagrilintide can’t be used in compounding under federal law^[52].

“Natural GLP-1” supplements are not GLP-1 medications. Supplements, drops or patches marketed that way haven’t been approved or evaluated for safety and effectiveness. In December 2024, the FDA sent a warning letter to a company selling weight-loss drops promoted with “The Science of GLP-1” and an “FDA APPROVED” badge. The agency found they were unapproved new drugs with false or misleading labeling^[53]. The same FDA page warns about fraudulent products labeled as compounded semaglutide or tirzepatide, some naming pharmacies that don’t exist^[52].

Frequently asked questions

Is Ozempic a GLP-1?

Yes. Ozempic is semaglutide, a GLP-1 analog that switches on the GLP-1 receptor. In the US, it’s approved for adults with type 2 diabetes, including to lower heart and kidney risk in some of them^[17]. Wegovy is the same molecule at different doses, approved for weight management; Rybelsus and Ozempic tablets are the pill versions for diabetes^[16,18].

Is Ozempic approved for weight loss?

No. Its US label covers only uses tied to type 2 diabetes^[17]. The semaglutide approved for weight management is Wegovy, as a weekly injection (since 2021) or a daily tablet (since December 2025)^[10,11]. Using Ozempic for weight loss is off-label: outside what the FDA reviewed for that product. Which drug fits you is a question for your prescriber.

Is Mounjaro or Zepbound a GLP-1?

Partly. Tirzepatide, the drug in both, activates the GLP-1 receptor and the GIP receptor, which is why it’s called a dual agonist. In everyday speech it’s lumped in with “the GLP-1s”, and it shares their main effects and most of their warnings. Mounjaro is the brand for type 2 diabetes and Zepbound the one for weight management and sleep apnea^[19,20].

Which GLP-1 is the strongest?

Among approved drugs, the largest average weight losses in people without diabetes are with tirzepatide and semaglutide 2.4 mg (see the trial table). The head-to-head trial in obesity, SURMOUNT-5, found 20.2% with tirzepatide vs. 13.7% with semaglutide^[43]. But “strongest” doesn’t mean “best for you”: tolerance, your other health conditions and the approved use all matter, and that’s for your appointment.

Are there GLP-1 pills?

Yes. In the US: Rybelsus and Ozempic tablets (semaglutide) for type 2 diabetes^[18]; Wegovy tablets (semaglutide) for weight management, approved December 22, 2025^[11]; and Foundayo (orforglipron) for weight management, approved April 1, 2026^[14]. In the EU, Rybelsus and Wegovy tablets are authorized^[28,29], and orforglipron is under review^[34].

What’s the difference between a GLP-1 agonist, a GLP-1 analog and a “GLP-1 drug”?

A GLP-1 receptor agonist is any drug that switches on that receptor. A GLP-1 analog is an agonist that also resembles the hormone, like semaglutide or liraglutide; orforglipron is an agonist but not an analog. GLP-1 drug is the everyday term, which usually includes tirzepatide.

Do they work for type 1 diabetes?

They aren’t approved for it: none of the US or EU labels I reviewed lists it as an indication. The US Wegovy label notes that use in patients with type 1 diabetes has not been evaluated^[16], and the EU Trulicity label says dulaglutide should not be used in patients with type 1 diabetes^[33]. If you have type 1 diabetes, take any questions about these drugs to your endocrinologist.

Are GLP-1 medications only for people with diabetes?

No. Some are approved only for type 2 diabetes, such as Ozempic (see Is Ozempic approved for weight loss?), and others for weight management whether or not you have diabetes. The US labels for Wegovy, Zepbound and Saxenda approve them to reduce excess body weight and maintain weight reduction long term in adults with obesity, or with overweight and at least one weight-related comorbid condition, alongside a reduced-calorie diet and more physical activity^[16,20,21]. The full list of approved uses is in what they’re approved for. Whether one fits you is your prescriber’s call.

Is it dangerous to take them for years without diabetes?

Trials in people without diabetes run to about four years. In SELECT, in adults with cardiovascular disease, semaglutide 2.4 mg was linked to fewer serious adverse events than placebo through week 208, but more people stopped taking it^[72]. In STEP 5, over 104 weeks, digestive side effects, mostly mild to moderate, affected 82.2% on semaglutide vs. 53.9% on placebo^[71]. In SURMOUNT-1, after 176 weeks of tirzepatide in people with obesity and prediabetes, no new safety signals were identified^[73]. The Wegovy and Zepbound labels cover maintaining weight reduction long term and set no maximum duration^[16,20]. Beyond those timelines, there’s no data. Talk to your prescriber about how long to continue; more in the long-term effects answer and Do you have to stay on the medication for life?.

What happens if you stop taking them?

Appetite comes back and, on average, much of the weight does too. In the STEP 1 extension (study summary), a year after stopping semaglutide and the lifestyle program, participants had regained about two-thirds of the weight they’d lost^[39]. Stopping is a decision to make with your prescriber. More in what happens when you stop Ozempic, Wegovy or Zepbound.

Do I need to change what I eat?

It helps a lot. With less appetite, each meal needs to deliver more: enough protein, fiber and fluids. There’s a full guide to what to eat on GLP-1 medications, plus nutrient data for each food in our food pages and the protein calculator to estimate how much you need.