GLP-1 medications for weight loss: how they work and who they suit

What these medications are

GLP-1 receptor agonists are injectable or oral medicines that imitate glucagon-like peptide-1, a hormone your gut releases after you eat. They were developed for type 2 diabetes. The weight effect was noticed in those diabetes trials, studied properly, and eventually approved as an indication of its own.

That history explains a lot of the confusion around them. The same molecule is often sold under two brand names at two different doses for two different conditions, which is why Ozempic and Wegovy keep getting discussed as though they were different drugs.

How the class works

Binding the GLP-1 receptor does several things at once. It prompts insulin release when blood glucose is high, suppresses glucagon, slows the rate at which the stomach empties, and acts on appetite regulation in the hypothalamus and hindbrain.

What that feels like is getting full sooner, staying full longer, and thinking about food less. The reduction in what researchers call food noise is the effect people describe most often and the one that is hardest to capture in a trial endpoint.

The slowed stomach emptying is also where most of the nausea comes from, which is why every one of these drugs is started low and raised slowly rather than begun at the dose it ends at.

What is approved for weight management

• Semaglutide 2.4 mg weekly, sold as Wegovy, approved by the FDA in 2021. The same molecule at lower doses is Ozempic for type 2 diabetes.
• Tirzepatide up to 15 mg weekly, sold as Zepbound, approved in 2023. It agonises both the GIP and GLP-1 receptors, so it is a dual agonist rather than a pure GLP-1, and it is grouped with the class by convention.
• Liraglutide 3.0 mg daily, sold as Saxenda, approved in 2014. The oldest of the three and now largely superseded, but it is available as a generic in some markets, which changes the cost picture.
• Oral semaglutide 50 mg daily was studied for weight management in the OASIS programme. Rybelsus, the existing oral tablet, is approved for type 2 diabetes at lower doses.

What the trials actually found

Mean weight change over roughly the same trial length, in adults without diabetes, against placebo:

• Semaglutide 2.4 mg: about 15% at 68 weeks in STEP 1, against roughly 2.4% on placebo. Around a third of participants lost 20% or more.
• Tirzepatide 15 mg: about 20.9% at 72 weeks in SURMOUNT-1, against roughly 3% on placebo.
• Liraglutide 3.0 mg: about 8% at 56 weeks in the SCALE programme.
• Two things get lost when these numbers are quoted. They are means, and the spread around them is wide, with a meaningful minority of people responding much less than the average. And people with type 2 diabetes consistently lose less on the same dose, which is a reproducible finding across the whole class rather than a quirk of one trial.

Benefits that are not weight

The most consequential result in this field was not a weight result. SELECT randomised 17,604 adults with cardiovascular disease and overweight or obesity, but without diabetes, to semaglutide 2.4 mg or placebo. Major adverse cardiovascular events fell by about 20% over roughly three years.

That matters because it is the first hard outcome evidence in this population, and it changes the argument from cosmetic to cardiovascular. Tirzepatide has a separate indication for moderate to severe obstructive sleep apnoea with obesity, granted in 2024 on the strength of its own trial.

Where the risks actually sit

The gastrointestinal effects are near universal and mostly manageable. The things worth understanding are the less common ones.

• Pancreatitis and gallbladder disease. Gallbladder and biliary events occur more often than on placebo, and the risk rises with faster weight loss. Severe persistent abdominal pain, particularly radiating to the back, needs assessment rather than waiting.
• A boxed warning for thyroid C-cell tumours, based on rodent studies. Human relevance is not established, but the contraindication for medullary thyroid carcinoma and MEN2 is absolute.
• Aspiration under anaesthesia. Retained stomach contents raise the risk during sedation, and anaesthetic guidance changed as a result. Tell any surgical team you are on one of these.
• Dehydration from vomiting or diarrhoea, which is the mechanism behind a meaningful share of the serious adverse events. Acute kidney injury in this setting is preventable and is mostly about fluids.
• A signal for non-arteritic anterior ischaemic optic neuropathy, a rare eye condition, reported in 2024 and reviewed by European regulators, who concluded it is a very rare side effect. Sudden vision loss is an emergency regardless of cause.
• Reports of suicidal ideation prompted formal reviews by both the FDA and the European Medicines Agency. Both concluded the available evidence does not support a causal association. That is a reassurance, not a dismissal, and anyone whose mood changes on these drugs should say so.

Who they are for

The approved criteria in the United States are a BMI of 30 or above, or 27 or above with at least one weight-related condition such as hypertension, type 2 diabetes, dyslipidaemia or obstructive sleep apnoea. Wegovy also carries an adolescent indication from age 12.

BMI is a blunt instrument and everyone involved knows it. It is the entry criterion because it is what the trials enrolled on, not because it is a good description of an individual.

What happens when you stop

This is the part most coverage skips. In the STEP 1 trial extension, participants who came off treatment regained about two thirds of the weight they had lost within a year, and the cardiometabolic improvements largely went with it. STEP 4 showed the mirror image: people who continued kept losing, and those switched to placebo regained.

Read together, these are the clearest evidence that this is a treatment for a chronic condition rather than a course with an end date. Whatever you think about that, it is the finding to plan around.

What is still unknown

• What ten or twenty years of continuous use looks like. The longest randomised data runs to about two years.
• How much of the lost weight is lean mass over long periods, and what that means for people who are already older or sarcopenic.
• Whether there is a way to stop without regaining, which nobody has yet demonstrated.
• How the outcome benefits distribute across groups who were underrepresented in the trials.

Sources

• Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021;384(11):989-1002.
• Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). N Engl J Med. 2022;387(3):205-216.
• Lincoff AM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT). N Engl J Med. 2023;389(24):2221-2232.
• Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564.
• Rubino D, et al. Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance (STEP 4). JAMA. 2021;325(14):1414-1425.
• He L, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases. JAMA Intern Med. 2022;182(5):513-519.
• Sodhi M, et al. Risk of Gastrointestinal Adverse Events Associated With GLP-1 Receptor Agonists for Weight Loss. JAMA. 2023;330(18):1795-1797.
• Hathaway JT, et al. Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmol. 2024;142(8):732-739.
• Wegovy (semaglutide) injection, prescribing information. Novo Nordisk.
• Zepbound (tirzepatide) injection, prescribing information. Eli Lilly.