Semaglutide

What is semaglutide?

Semaglutide is a GLP-1 receptor agonist made by Novo Nordisk. It is sold as Ozempic, a weekly injection for type 2 diabetes approved in 2017; Rybelsus, a daily tablet for type 2 diabetes approved in 2019; and Wegovy, a higher-dose weekly injection for chronic weight management approved in 2021. Wegovy is also approved to lower the risk of heart attack, stroke and cardiovascular death in people with established heart disease and overweight or obesity.

Semaglutide changed expectations for obesity medicine. Before it, approved weight-loss drugs typically produced average losses of around 10% or less. In the STEP 1 trial, people taking semaglutide 2.4 mg lost about 15% of their body weight over 68 weeks³. It has since become one of the most prescribed drugs in the US, and one of the most discussed.

How semaglutide works

After you eat, your gut releases a hormone called GLP-1. It tells the pancreas to release insulin when blood sugar is high, slows the rate at which food leaves the stomach, and signals the brain that you are full. Natural GLP-1 lasts only a couple of minutes in the blood. Semaglutide is a modified version that lasts about a week, so a single weekly injection keeps that 'I have eaten' signal switched on. People typically feel less hungry, get full sooner and think about food less.

Chemically, semaglutide shares about 94% of its sequence with human GLP-1. An alpha-aminoisobutyric acid substitution at position 8 protects it from breakdown by the enzyme DPP-4, and a C18 fatty diacid side chain binds it to albumin in the blood, slowing clearance and giving a half-life of about seven days. It stimulates glucose-dependent insulin secretion and suppresses glucagon, which lowers blood sugar with little risk of hypoglycemia on its own. Its weight effect comes mainly from GLP-1 receptors in the hypothalamus and brainstem that reduce appetite and energy intake, rather than from burning more calories. The oral version uses an absorption enhancer to survive the stomach.

What the research shows on semaglutide

Semaglutide has one of the largest evidence bases of any obesity drug. In STEP 1, 1,961 adults without diabetes received semaglutide 2.4 mg or placebo weekly for 68 weeks, alongside lifestyle support. Average weight change was -14.9% with semaglutide versus -2.4% with placebo, and half of those on the drug lost at least 15%³. In STEP 8, semaglutide produced -15.8% weight change compared with -6.4% for daily liraglutide, the previous standard².

The SELECT trial enrolled 17,604 people with heart disease and overweight or obesity but no diabetes. Over about 40 months, semaglutide cut major cardiovascular events (cardiovascular death, heart attack or stroke) by 20%, from 8.0% to 6.5%⁷. That made it the first obesity drug shown to reduce heart attacks and strokes in this population.

The trials also show limits. Weight returns when treatment stops. In STEP 4, people who switched to placebo after 20 weeks regained 6.9% of body weight over the next 48 weeks, while those who continued lost a further 7.9%⁴. In the STEP 1 extension, participants regained about two-thirds of their lost weight within a year of stopping, and most cardiometabolic improvements faded¹. This points to obesity as a chronic condition needing ongoing treatment.

Newer drugs now outperform it on weight. In SURMOUNT-5, tirzepatide produced -20.2% weight change versus -13.7% for semaglutide at 72 weeks⁵, and tirzepatide also lowered HbA1c and weight more than semaglutide 1 mg in type 2 diabetes⁸. A higher 7.2 mg semaglutide dose produced -18.7% weight change in the STEP UP trial, compared with -15.6% on 2.4 mg⁶. Nearly all the major trials were funded by the manufacturers.

Studied for: Type 2 diabetes, Chronic weight management, Cardiovascular risk reduction.

Semaglutide reference data

Semaglutide dosage in published research

How semaglutide is used in practice

Semaglutide is started at a low weekly dose and increased every four weeks over about 16 weeks to reduce nausea. Branded pens are prescribed by primary care doctors, endocrinologists, obesity specialists and many telehealth services. Cost and insurance coverage remain major barriers, particularly for weight management, and manufacturer direct-to-consumer cash programs have expanded access somewhat.

During the national shortage from 2022 to early 2025, compounding pharmacies were allowed to make copies, and many telehealth companies sold compounded semaglutide at lower prices. The FDA declared the shortage resolved in February 2025, which sharply restricted routine compounding. Some compounded products had used salt forms such as semaglutide sodium that differ from the approved drug, and FDA received reports of dosing errors with multi-dose vials. Semaglutide is also sold online as a research chemical, with no guarantee of content or sterility.

Semaglutide risks and side effects

Gastrointestinal effects are the most common: nausea, diarrhea, vomiting, constipation and abdominal pain. In STEP 1 they were usually mild to moderate and eased with time, but 4.5% of semaglutide users stopped treatment because of them, compared with 0.8% on placebo³. In SELECT, 16.6% of semaglutide users discontinued because of adverse events versus 8.2% on placebo⁷. At 7.2 mg, unpleasant skin sensations (dysesthesia) were reported by 22.9% of participants⁶.

Less common but more serious risks include pancreatitis, gallbladder disease, kidney injury from dehydration, and worsening diabetic retinopathy in people with existing eye disease and rapid blood sugar improvement. The label carries a boxed warning about thyroid C-cell tumors seen in rodents, so it is not used by people with a personal or family history of medullary thyroid carcinoma or MEN2. Slowed stomach emptying can affect oral drug absorption and raise aspiration risk during anesthesia. Combined with insulin or sulfonylureas, it increases hypoglycemia risk. It should be stopped before a planned pregnancy. Weight loss includes some muscle loss, so protein intake and resistance exercise matter.

Reported side effects

Alternatives to semaglutide

Tirzepatide (Zepbound, Mounjaro) is the main alternative and produced greater weight loss in a direct comparison⁵. Liraglutide (Saxenda, Victoza) is a daily GLP-1 drug with lower efficacy but generic versions. Older oral options include phentermine-topiramate and naltrexone-bupropion. Metabolic and bariatric surgery remains the most effective long-term treatment for severe obesity. For type 2 diabetes, SGLT2 inhibitors and metformin are common alternatives or companions.

Questions for a clinician

• What evidence applies to my situation, and at what level?
• What established alternatives should I consider first?
• What monitoring would be necessary, and how often?