Few medicines have drawn as much attention as the GLP-1 class. Behind the headlines is a real advance in obesity medicine, and some real questions about who should use these medicines and how.
What GLP-1 actually is
Glucagon-like peptide-1 (GLP-1) is a hormone released by the gut after eating. It signals fullness to the brain, slows how quickly the stomach empties and helps regulate blood sugar. GLP-1 receptor agonists such as semaglutide and liraglutide mimic this signal for much longer than the natural hormone. Tirzepatide acts on both the GLP-1 receptor and the receptor for a second gut hormone, GIP.
The practical effect for many people is that hunger quiets down and smaller portions feel satisfying. That makes the rest of the plan, food choices, activity and habits, easier to sustain.
These medicines don’t replace effort. They change the biology that has been working against it.
What the major trials found
In the STEP 1 trial, 1,961 adults with obesity or overweight (without diabetes) received weekly semaglutide or placebo for 68 weeks, both alongside lifestyle support. Average body-weight change was −14.9% with semaglutide versus −2.4% with placebo.[1] In SURMOUNT-1, 2,539 adults without diabetes received tirzepatide or placebo for 72 weeks. Average weight change ranged from about −15% to −21% across the three doses studied, compared with −3.1% on placebo.[2]
These are group averages from carefully run trials. Some people respond more, some less, and a few stop because of side effects. They are not a prediction for any one person.
Who these medicines are for
Clinical guidelines consider anti-obesity medication for adults with a body mass index (BMI) of 30 or higher, or 27 or higher with a weight-related condition such as type 2 diabetes, high blood pressure, abnormal cholesterol or sleep apnea, as an add-on to a lifestyle program.[4] The American Gastroenterological Association suggests adding medication for adults with obesity who haven’t had an adequate response to lifestyle changes alone.[3]
They are not right for everyone. GLP-1 and GIP/GLP-1 medications aren’t used during pregnancy or in people with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2, and a careful history matters for anyone with past pancreatitis or gallbladder disease.[3]
Side effects and safety
- Digestive symptoms such as nausea, vomiting, diarrhea and constipation are the most common, especially when the dose is increased. They often ease with time.
- Gallbladder problems and pancreatitis are less common but serious. Know the warning signs listed below.
- Dehydration can follow vomiting or diarrhea and may affect the kidneys, so fluids matter.
- Low blood sugar is uncommon on these medicines alone but more likely with insulin or sulfonylureas, which may need adjusting.
What happens if you stop
In the STEP 1 extension, people who stopped semaglutide regained about two-thirds of the weight they had lost within a year, and some of the improvements in blood pressure and blood sugar faded too.[5] That is why guidelines treat these medicines as long-term therapy for a chronic disease, and why a plan for maintenance is part of the conversation from the start.
Sources and references
- Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al.; STEP 1 Study Group. Once-weekly semaglutide in adults with overweight or obesity. N Engl J Med. 2021;384(11):989-1002. View source
- Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, et al.; SURMOUNT-1 Investigators. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387(3):205-216. View source
- Grunvald E, Shah R, Hernaez R, Chandar AK, Pickett-Blakely O, Teigen LM, et al.; AGA Clinical Guidelines Committee. AGA clinical practice guideline on pharmacological interventions for adults with obesity. Gastroenterology. 2022;163(5):1198-1225. View source
- Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD. Pharmacological management of obesity: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2015;100(2):342-362. View source
- Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, et al.; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: the STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. View source
This answer is general education for adults and isn’t a substitute for a personal medical evaluation. Individual results vary. In an emergency, call 911.