Weight-Loss Medications: GLP-1s and the Rest, Explained

The short version

• Modern medications such as semaglutide and tirzepatide produced average weight loss of about 15 to 21% in major trials.
• They're generally for adults with a BMI of 30 or more, or 27 or more with a weight-related condition.
• Stomach side effects are common, and serious risks are possible, so these need medical supervision.
• Most people regain weight after stopping, and they should be thought of as long-term treatment.

Who they're for

Most prescription options are approved for adults with:

• A BMI of 30 or more, or
• A BMI of 27 or more with a weight-related condition such as high blood pressure, type 2 diabetes or high cholesterol.

They're meant to be used along with changes to eating and activity. Some are also approved for teens. These aren't for cosmetic loss in people at a healthy weight.

How GLP-1 medications work

Your gut makes hormones after you eat, and these signal fullness to your brain and regulate blood sugar. GLP-1 medications imitate one of those hormones. Tirzepatide also acts on a second one, GIP. People often describe less "food noise," smaller appetites and feeling full sooner.

This doesn't mean a lack of willpower caused the problem. It suggests that appetite is biology, and biology can be treated.

The main options

These are trial averages, and individual results differ widely. Some people lose much more, and others barely respond. Ozempic and Mounjaro are the diabetes brands of semaglutide and tirzepatide. If you haven't lost at least 5% of your weight after 12 weeks on the full dose, your prescriber will probably suggest stopping or switching.

Benefits beyond the scale

In the SELECT trial of 17,604 adults with heart disease and overweight or obesity, but no diabetes, semaglutide lowered major cardiovascular events by 20%. Other uses include treating sleep apnea and fatty liver disease in some patients. Researchers continue to study more conditions.

Side effects and risks

Common: Nausea, vomiting, diarrhea, constipation, and reflux. These are usually strongest as doses go up, and doses are raised slowly for this reason. In the SELECT trial, about 17% of people on semaglutide stopped because of side effects, compared with about 8% on placebo.

Less common but serious: Pancreatitis, gallbladder disease, kidney problems from dehydration, and severe stomach problems. The labels of these drugs include warnings to watch for.

Boxed warning: GLP-1 medications carry a warning about thyroid C-cell tumors, seen in rodents. Don't use them if you or a family member has had medullary thyroid cancer, or if you have MEN2 syndrome.

Birth control: Tirzepatide can make birth control pills less reliable. Its label advises switching to a non-pill method, or adding a barrier method, for 4 weeks after starting and for 4 weeks after each dose increase. Ask whether anything similar applies to your medication.

Also talk to your clinician about: Pregnancy plans, since these medications aren't for use during pregnancy and you should stop before trying to conceive, as directed by your clinician. They also aren't recommended while breastfeeding. Tell your surgical team before any anesthesia. And if you take insulin or sulfonylureas, your doses may need to change.

Mood: Report any changes in mood, or any thoughts of self-harm, right away.

Protecting your muscle

Rapid weight loss on any treatment takes some muscle with it. Eat enough protein, even if your appetite is small, and do strength training. Stay hydrated, and choose nutritious foods since you may be eating less overall.

What happens when you stop

In the STEP 1 extension, people regained about two-thirds of the lost weight within a year of stopping. Appetite tends to come back. So this is more like a blood pressure drug than a course of antibiotics. If you need to stop, for example because of cost, plan it with your prescriber and build up your maintenance habits first.

Avoid fakes and unapproved copies

Sources

1. NIDDK: Prescription Medications to Treat Overweight and Obesity
2. Wilding et al., NEJM (2021): Once-weekly semaglutide in adults with overweight or obesity (STEP 1)
3. Jastreboff et al., NEJM (2022): Tirzepatide once weekly for obesity (SURMOUNT-1)
4. Lincoff et al., NEJM (2023): Semaglutide and cardiovascular outcomes (SELECT)
5. Wilding et al., Diabetes Obes Metab (2022): Weight regain after stopping semaglutide
6. FDA: Approval of orforglipron (Foundayo), April 2026
7. American College of Cardiology: OASIS 4 trial summary
8. American College of Cardiology: ATTAIN-1 trial summary
9. Lilly Medical: Zepbound and oral contraceptives
10. FDA: Concerns With Unapproved GLP-1 Drugs Used for Weight Loss

This guide is general information, not medical advice. Please check with a clinician before making big changes, especially if you have a health condition, take medication, or are pregnant. Read the full disclaimer.