GLP-1 Medications for Weight: Semaglutide and Tirzepatide Explained

You may have tried many times to lose weight, and the weight kept coming back. Now you hear about weekly shots that help people lose 15% or more. You want to know if they work, if they are safe, and if they are right for you. This guide explains what the trials showed and what clinicians weigh.

What these medicines are

GLP-1 is a hormone your gut makes after you eat. GLP-1 medicines act like this hormone, but they last much longer.

• Semaglutide is a GLP-1 receptor agonist. For weight management, it is sold as Wegovy. A lower-dose version for diabetes is sold as Ozempic.
• Tirzepatide acts on GLP-1 and a second gut hormone receptor, GIP. For weight management in the US, it is sold as Zepbound [6]. For diabetes, it is sold as Mounjaro.

These medicines:

• Reduce hunger and help you feel full sooner
• Slow how fast food leaves the stomach
• Lower blood sugar when it is high

Most are injected once a week, with the dose raised slowly over several months.

What the trials showed

Semaglutide

In the STEP 1 trial, about 2,000 adults with obesity, or overweight with a related health problem, took weekly semaglutide 2.4 mg or placebo for 68 weeks [1]. Everyone also got lifestyle support.

• Average weight loss was 14.9% with semaglutide and 2.4% with placebo [1].
• About 1 in 3 people on semaglutide lost 20% or more [1].

Tirzepatide

In the SURMOUNT-1 trial, about 2,500 adults with obesity, or overweight with a related problem, took tirzepatide or placebo for 72 weeks [2].

• Average weight loss was about 15%, 19.5%, and 20.9% with the 5 mg, 10 mg, and 15 mg doses [2].
• Weight loss with placebo was about 3% [2].

Heart benefits

The SELECT trial studied about 17,600 adults with heart disease and overweight or obesity, but without diabetes [3]. Over about 3 years, semaglutide lowered heart attacks, strokes, and heart deaths together from 8.0% to 6.5% [3]. That is a 20% relative reduction.

What happens after stopping

In the STEP 1 extension, people stopped semaglutide and lifestyle support after 68 weeks. One year later, they had regained about two thirds of the weight they had lost [4]. Blood pressure and blood sugar gains also faded [4]. This is why obesity is treated as a long-term condition.

What your doctor looks at

Who may qualify

• In the US, FDA-approved labels for weight management generally cover adults with a BMI of 30 or higher, or 27 or higher with at least one weight-related condition, such as high blood pressure, type 2 diabetes, or high cholesterol [6].
• The 2020 Canadian adult obesity guideline from Obesity Canada says medicines can be used with lifestyle therapy for adults with a BMI of 30 or higher, or 27 or higher with weight-related complications [5].
• The Canadian guideline also stresses that obesity care should focus on health and complications, not on weight or BMI alone [5].

Approved products and coverage differ between Canada and the US. Ask your clinician or pharmacist which products are approved and covered where you live.

Side effects

The most common side effects are in the gut [1] [2]:

• Nausea, vomiting, diarrhea, and constipation, mostly when starting or raising the dose
• Feeling full quickly or losing interest in food

Less common but more serious risks include:

• Gallbladder problems, such as gallstones
• Pancreatitis
• Dehydration from vomiting or diarrhea, which can strain the kidneys
• The US labels carry a boxed warning about thyroid C-cell tumours seen in rodents. These drugs are not used in people with a personal or family history of medullary thyroid cancer or a condition called MEN 2.

Some of the weight lost is muscle, not only fat. Eating enough protein and doing strength exercise can help protect muscle.

Pregnancy

These medicines are not used during pregnancy. If you could become pregnant, ask your clinician how far ahead to stop before trying to conceive. Tirzepatide may also make birth control pills less effective at certain times. Ask your pharmacist.

Living with treatment

Many people find that side effects ease after the first weeks at each dose. Tips that often help with nausea:

• Eat smaller meals, and stop when you first feel full.
• Eat slowly.
• Avoid very fatty, fried, or greasy foods.
• Drink enough fluids, especially if you have vomiting or diarrhea.
• Ask whether a slower dose increase would help.

Because you may eat much less, it is important to get enough protein, fruits, vegetables, and fluids. A dietitian can help.

Questions to ask your clinician

• Do I meet the criteria for a weight medicine?
• Which medicine would suit me best, and why?
• What side effects should I expect, and how can I manage them?
• How long would I need to take it?
• What happens if I stop?
• How can I protect my muscle while I lose weight?
• Is it covered by my plan, and what are lower-cost options?

When to get care quickly

Go to the emergency department for:

• Severe belly pain, especially if it spreads to the back
• Pain in the upper right belly with fever or yellow skin or eyes
• Vomiting that will not stop, or signs of dehydration such as very little urine or dizziness
• Signs of a severe allergic reaction, such as swelling of the face or trouble breathing

Bottom line

Semaglutide and tirzepatide lead to large weight loss for many people, and semaglutide lowered heart events in people with heart disease. Side effects are common but often ease with time. Weight tends to return after stopping, so treatment is usually long term. Talk to your clinician or pharmacist before you start or stop any of these medicines.

Primary AI can show you the guideline and study sources behind this topic in plain language, so you can bring better questions to your appointment.