GLP-1 medications have transformed the treatment of obesity. Medications such as semaglutide (Wegovy) and tirzepatide (Zepbound) can produce substantial weight loss, but deciding whether to start one involves more than looking at a number on the scale.

If you’re considering one of these medications, it’s worth understanding how they work, how much weight people typically lose, what side effects to expect, and what treatment may look like over the long term.

What are GLP-1 medications?

GLP-1, or glucagon-like peptide-1, is a hormone your body naturally releases after you eat. GLP-1 medications work in part by changing the signals between your gut and brain that regulate hunger and fullness. Medications that act on this pathway can reduce appetite, help you feel full sooner and slow the rate at which food leaves your stomach.

Two commonly used medications for chronic weight management are:

• Semaglutide (Wegovy) — acts on the GLP-1 receptor.

• Tirzepatide (Zepbound) — acts on both GLP-1 and GIP receptors.

Tirzepatide is therefore technically a dual GIP/GLP-1 receptor agonist rather than a GLP-1–only medication, although the drugs are commonly discussed together.

How much weight can you lose?

The amount of weight you lose depends on the medication, dose, duration of treatment and your individual response. Clinical trials can give us a useful benchmark, but they can’t predict exactly how much weight one person will lose.

In a large clinical trial named the “STEP 1 trial”, adults with obesity who received semaglutide 2.4 mg plus lifestyle intervention lost an average of about 15% of their starting body weight over 68 weeks, compared with about 2% among those receiving placebo plus lifestyle intervention.

In the SURMOUNT-1 trial, participants receiving tirzepatide lost an average of approximately 15% to 21% of their starting body weight over 72 weeks, depending on the dose.

To put that into perspective, 15% weight loss for someone starting at 250 pounds would be about 38 pounds.

These are averages—not promises. Some people lose considerably more or less.

What are the most common side effects?

The most common side effects of GLP-1–based medications involve the gastrointestinal tract. These can include:

• Nausea

• Vomiting

• Diarrhea

• Constipation

• Abdominal discomfort

• Feeling full unusually quickly

• Indigestion or reflux

These symptoms are especially common when treatment is started or the dose is increased. In clinical trials, most gastrointestinal side effects were mild to moderate and occurred primarily during dose escalation.

However, a recent dose increase is not the only reason to consider the medication when new symptoms develop. GLP-1–based therapies can slow gastric emptying, and some patients may develop nausea, vomiting, or early satiety even after previously tolerating the same dose.

If significant gastrointestinal symptoms develop later in treatment, the medication should still be considered as one possible contributor while other causes are evaluated.

Are there serious risks?

Most people who take GLP-1–based medications experience gastrointestinal side effects rather than serious complications. However, there are several less common risks worth knowing about.

These can include:

• Pancreatitis: Inflammation of the pancreas can cause severe, persistent upper abdominal pain, sometimes radiating to the back, and may be accompanied by nausea or vomiting.

• Gallbladder problems: Rapid weight loss and GLP-1–based treatment have both been associated with gallstones and inflammation of the gallbladder. Symptoms can include persistent right upper abdominal pain, fever, nausea, or yellowing of the skin or eyes.

• Dehydration and kidney injury: Repeated vomiting or diarrhea can lead to significant fluid loss, which in some cases can contribute to acute kidney injury.

• Severe gastrointestinal symptoms: Because these medications slow gastric emptying, persistent vomiting, inability to tolerate food or liquids, or severe abdominal distention should not simply be assumed to be a routine medication side effect.

• Low blood sugar: Hypoglycemia is more likely when GLP-1–based medications are used with other glucose-lowering medications such as insulin or sulfonylureas.

Semaglutide and tirzepatide also carry a boxed warning regarding thyroid C-cell tumors based on findings in animal studies. It is not known whether these medications cause medullary thyroid carcinoma in humans. They should not be used in people with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

Seek prompt medical evaluation for severe or persistent abdominal pain, repeated vomiting, inability to keep fluids down, signs of dehydration, jaundice, or other symptoms that feel significantly different from the expected mild gastrointestinal effects of treatment.

Do you have to stay on a GLP-1 medication forever?

Not necessarily — but these medications are generally intended as long-term treatments for obesity rather than short-term weight-loss programs.

Obesity is a chronic condition, and the effects of GLP-1–based medications depend in part on continuing treatment. When the medication is stopped, appetite and other physiologic drivers of weight gain can return.

Studies have shown that weight regain is common after treatment is discontinued. In follow-up from the STEP 1 semaglutide trial, participants regained a substantial portion of the weight they had lost after stopping treatment. Similar findings have been seen with tirzepatide, where continued therapy was more effective at maintaining weight loss than withdrawal.

That does not mean every patient needs to stay on the same medication indefinitely. Treatment may change because of:

• Side effects

• Cost or insurance coverage

• Pregnancy or plans for pregnancy

• Changes in health status

• Inadequate response to treatment

• A decision to transition to another long-term weight-management strategy

The more useful question may be less “When can I stop?” and more “What is my long-term plan for maintaining the weight I lose?”

For some people, that plan may include continued medication. For others, it may involve changing medications or using other approaches under the guidance of a healthcare professional.

Who may be a candidate for treatment?

Prescription weight-management medications may be appropriate for some adults with obesity or overweight, particularly when excess weight is contributing to other health problems.

For medications such as semaglutide and tirzepatide, treatment is generally considered for adults with:

• A BMI of 30 kg/m² or higher, or

• A BMI of 27 kg/m² or higher with at least one weight-related medical condition, such as high blood pressure, high cholesterol, obstructive sleep apnea, or type 2 diabetes.

Meeting a BMI threshold does not automatically mean that medication is the right choice. A healthcare professional may also consider:

• Weight-related medical conditions

• Previous weight-management efforts

• Current medications

• Medical and family history

• Pregnancy or plans for pregnancy

• Potential medication interactions or contraindications

• Your goals, preferences, and ability to continue treatment long term

BMI is useful as a screening tool, but it does not tell the whole story. It does not directly measure body composition or fully capture how excess weight is affecting an individual’s health.

The decision to start medication should therefore be individualized rather than based on BMI alone.

The bottom line

GLP-1–based medications such as semaglutide and tirzepatide can produce meaningful weight loss and have become important tools for treating obesity.

They are not without tradeoffs. Gastrointestinal side effects are common, more serious complications can occur, and weight regain is common after treatment is stopped. These medications are also generally intended as part of a long-term weight-management strategy rather than a short-term fix.

If you are considering treatment, the most important questions are whether the medication is appropriate for your health history, whether you understand the potential benefits and risks, and whether you have a realistic plan for monitoring and maintaining your progress over time.

A healthcare professional can help determine whether treatment is appropriate and how it fits into your broader approach to weight management.

References

1. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-216.

2. Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24:1553-1564.

3. Aronne LJ, Sattar N, Horn DB, et al. Continued treatment with tirzepatide for maintenance of weight reduction in adults with obesity: The SURMOUNT-4 randomized clinical trial. JAMA. 2024;331:38-48.

4. Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs tirzepatide for weight loss in adults with overweight or obesity. JAMA Intern Med. 2024;184:1056-1064.

5. U.S. Food and Drug Administration. Wegovy (semaglutide) prescribing information. FDA; 2026.

6. U.S. Food and Drug Administration. Zepbound (tirzepatide) prescribing information. FDA; 2026.

7. U.S. Food and Drug Administration. FDA’s concerns with unapproved GLP-1 drugs used for weight loss. FDA; 2026.

This sample is intended to demonstrate patient-facing clinical content development and is for informational purposes only. It is not a substitute for individualized medical advice.