What are GLP-1 medications like semaglutide and tirzepatide?

What they are

GLP-1 medications mimic GLP-1 (glucagon-like peptide-1), a hormone the gut releases after meals. GLP-1 is a peptide, a short chain of amino acids (the building blocks of proteins). The enzyme DPP-4 and the kidneys clear half of it from the blood within 1 to 2 minutes.^1,2

Semaglutide and tirzepatide are receptor agonists: they bind to a hormone’s receptor on cells and switch it on. Semaglutide closely matches human GLP-1 but is modified to resist DPP-4. Liraglutide, an earlier GLP-1 medication, is also modeled on human GLP-1. Tirzepatide is built on GIP (glucose-dependent insulinotropic polypeptide), a second gut hormone, and acts on both GIP and GLP-1 receptors.^3,4,5,57

Retatrutide, code name LY3437943, is an experimental peptide that acts on three receptors: GIP, GLP-1 and glucagon. Glucagon is a pancreatic hormone that raises blood sugar. Cagrilintide is an experimental peptide modeled on amylin, a pancreatic hormone that makes people feel full.^6,7,8,61,62

How they work

The semaglutide and tirzepatide labels say both drugs make the pancreas release more insulin and less glucagon when blood sugar is high. They slow how fast food leaves the stomach. GLP-1 receptors are also found in brain areas that control appetite, and both drugs lower calorie intake, likely by affecting appetite.^3,9,10

How they are taken

Semaglutide, tirzepatide and liraglutide are injected under the skin (a subcutaneous injection), from prefilled pens, syringes or vials. Semaglutide also comes as a tablet.^{3,4,9,11,57,58}

Orforglipron, also a GLP-1 tablet, is not a peptide but a small molecule, a compact chemical.^12,13,14

What the research in people shows

Most trials below supported FDA approvals; the drug’s maker paid for each.^{14,15,17,18,19,20,21,22,23,24,32,59,60,63,64}

People on these drugs lose lean mass, which includes muscle, along with fat. In a 2025 SURMOUNT-1 substudy, X-ray scans (DXA) of 160 participants after 72 weeks showed most weight lost was fat, on tirzepatide or placebo, though people on tirzepatide lost more of both. A 2026 meta-analysis found lean mass fell consistently with GLP-1 drugs across 28 studies, on low-certainty evidence, and called effects on muscle function unclear.^67,68

What happens after stopping

In STEP 4 (2021), 803 adults taking semaglutide were randomly assigned to continue it or switch to placebo for about a year. SURMOUNT-4 (2024) did the same with 670 adults taking tirzepatide. In both, those switched to placebo regained much of the lost weight, and those who continued kept losing weight.^26,27

A 2026 review of 37 studies with 9,341 adults found weight returned faster after stopping a weight-management medicine, including semaglutide and tirzepatide, than after diet and exercise programs ended.²⁸

Side effects and risks

Digestive side effects are the most common. Nausea affected 44 in 100 people on semaglutide injections in the three main weight-management trials, lasting up to 68 weeks, against 16 in 100 on placebo. Two tirzepatide trials lasting up to 72 weeks found 25 to 29 in 100, against 8. Diarrhea, vomiting and constipation were also more common.^9,10

Most were mild to moderate and eased over time. In those trials, about 7 in 100 people on semaglutide and 5 to 7 in 100 on tirzepatide stopped because of side effects, against about 3 on placebo. Other common effects include stomach pain, indigestion, tiredness, dizziness, hair loss and, with semaglutide, abnormal skin sensations (dysesthesia).^9,10,17,18

Every semaglutide, tirzepatide and liraglutide label carries a boxed warning, which the FDA can require for serious risks, even ones seen only in animals. In rodents, all three drugs caused tumors of the thyroid’s C-cells (cells that make the hormone calcitonin), including cancers. The drugs must not be used by anyone with a personal or family history of medullary thyroid cancer, or with multiple endocrine neoplasia type 2 (MEN 2), an inherited tumor syndrome. Nor may anyone who has had a serious allergic reaction to the drug use it. The labels also warn about:^{3,4,9,10,11,29,30,57,58}

In November 2026 the FDA required a warning about a potential increased risk of NAION (non-arteritic anterior ischemic optic neuropathy) on all GLP-1 medications. NAION is sudden, painless vision loss in one eye from reduced blood flow to the optic nerve, and it can be permanent.²

In the FDA’s analysis of 126 randomized trials, there were 6.4 NAION cases for every 100,000 people treated for a year with a GLP-1 drug, against 3.8 with comparison treatments. Those rates rest on 15 probable cases. The FDA’s own study of adults with type 2 diabetes, and well-designed published ones, found higher risk than with some other diabetes drugs. NAION is more likely to recur in people who have had it, and the FDA advises clinicians to consider stopping the drug if it occurs.²

In February 2026 the weight-management labels dropped a warning about suicidal thoughts and behavior, at the FDA’s request. Its review of 91 placebo-controlled trials with 107,910 people found no increased risk.^9,10,31,58

The weight-management labels say to stop once a pregnancy is recognized. The semaglutide labels advise stopping at least 2 months before a planned one. Tirzepatide can make birth-control pills less reliable, so its labels advise a non-oral or added barrier method for 4 weeks after starting and after each dose increase. The semaglutide tablet labels advise against breastfeeding.^4,9,10,11,58

By slowing stomach emptying, the drugs can change how other medicines taken by mouth are absorbed. The labels advise closer checks on drugs with a narrow safe range, such as the blood thinner warfarin. Semaglutide tablets raised exposure to the thyroid medicine levothyroxine by about a third in one study. The weight-management labels advise against combining them with other GLP-1 medicines.^4,9,10,11,58

Retatrutide’s and cagrilintide’s side effects were also mostly digestive. In TRIUMPH-2, up to 6 in 100 people on retatrutide had low blood pressure and up to 7 in 100 abnormal skin sensations, against 1 in 100 or fewer on placebo. Serious health problems were more common with retatrutide in two 2026 knee osteoarthritis trials.^25,32,62,63

FDA status

The FDA has approved semaglutide and tirzepatide products for the uses below. Liraglutide products were approved for type 2 diabetes in 2010, chronic weight management in 2014, and lowering heart risk in adults with type 2 diabetes and cardiovascular disease in 2017. Other companies’ liraglutide products have been approved since December 2024. No approval covers a compounded version of any of them, one made by a compounding pharmacy rather than the approved product’s manufacturer.^{3,4,33,34,35,36,53,54,55,57,58}

Accelerated approval, used for serious conditions with an unmet medical need, rests on a measure thought to predict real benefit, here liver biopsy results. Keeping it may depend on a further trial confirming that benefit.^9,41

Orforglipron tablets were approved on April 1, 2026, only for chronic weight management in adults with obesity, or with overweight and a weight-related condition.^12,13

Retatrutide and cagrilintide are not FDA-approved or part of any approved drug. “Retatrutide and cagrilintide cannot be used in compounding under federal law,” the FDA says. It has warned telehealth companies for marketing retatrutide, ingredient distributors for selling it to compounders, and outsourcing facilities (FDA-registered compounders) for repackaging it.^34,36

Compounded versions

The FDA does not review compounded drugs for safety, effectiveness or quality before they are sold. It says they “should only be used in patients whose medical needs cannot be met by an FDA-approved drug.”³⁴

Federal law restricts compounding that copies an approved drug, but the restriction lifts while the drug is on the FDA’s shortage list. Semaglutide and tirzepatide, listed from 2022, came off in February 2025 and late 2024 respectively, so copying them is again restricted. A federal appeals court upheld both decisions in August 2026. Liraglutide injection has been listed since July 2023 and still was on November 14, 2026.^{36,42,43,44,56}

A September 2026 FDA warning letter said a pharmacy’s tirzepatide with niacinamide, a B vitamin, and semaglutide with B12 appeared to be copies. It said ready-made menus of prescriber statements justifying such changes, on third-party technology platforms, call into question whether each decision was made for the individual patient.^42,45

By May 31, 2026, the FDA had received more than 1,700 reports of health problems with compounded semaglutide and tirzepatide. It says such problems are likely underreported, and it cannot always tell whether the drug caused them.³⁴

A 2026 study of compounders’ websites, searched in February and March 2025, found 33 compounded semaglutide and tirzepatide products that differed from approved ones in strength, route or form. About half added ingredients such as vitamin B12, and most others were meant to dissolve under the tongue (sublingual). The authors found little evidence on their safety or effectiveness.⁴⁶

FDA-approved semaglutide tablets contain an added ingredient that helps absorption in the stomach, yet their labels estimate no more than 2 parts in 100 reach the blood. In a May 2026 proposal on outsourcing facilities, the FDA found no basis to conclude that patients medically need semaglutide or tirzepatide held under the tongue or inside the cheek (buccal).^9,11,69

What isn’t known

Questions to ask a clinician