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January 20, 2024

Weight Loss Medication Side Effects: Know Before You Start

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Anti-obesity medications help many patients lose weight and keep it off. Medication can be part of a comprehensive obesity treatment plan. If you treat patients for overweight or obesity, you likely have patients asking you about these drugs, including newer ones like semaglutide and liraglutide. These medications are frequently in the news, and one topic that tends to arise is the side effects.

Research has begun to analyze side effects, particularly for GLP-1 agonists like semaglutide. For example, a paper published in late 2023 in JAMA quantified gastrointestinal adverse events ranging from nausea to pancreatitis.

Because stopping one of these medications comes with a high risk of weight regain, a person taking them should understand the risks.

If a patient is hesitant to try a certain medication due to concerns about side effects, you may wish to prescribe an alternative. There are many options available that target different mechanisms of hunger, fullness, and weight loss. Finding a medication that meets a patient’s individual needs is important for successful outcomes.

If you are a provider prescribing a weight loss medication, or you’re someone considering asking your doctor about a weight loss medication, familiarize yourself with the potential side effects. This information can help you prepare and understand what to expect.

Who Qualifies for Weight Loss Medications?

Eligibility for weight loss medications is typically based on body mass index (BMI). provides an Adult BMI Calculator.

For semaglutide or liraglutide, a patient must must be an adult or child age 12 or more, with a BMI of 30 or greater or with a BMI of 27 or greater with comorbidities such as high blood pressure, diabetes, or high cholesterol. People who have a BMI of 30 or above do not need to have a chronic disease associated with their BMI, because obesity is considered a chronic disease.

Requirements are similar for many other weight loss medications, including phentermine, naltrexone-bupropion, and orlistat, although not all are FDA-approved for use in children.

The more recently approved tirzepatide is approved only for adults with a BMI of 30 or greater. Note that tirzepatide is both a GLP-1 and a GIP receptor agonist, as are other medications currently in the pipeline.

Growing Concern over Digestive Side Effects of Popular Weight Loss Medications

As medications are on the market longer, knowledge of their side effects increases. However, with much attention on GLP-1 receptor agonists as well as GIP receptor agonists, patients are likely to ask about their side effects.

A 2023 analysis found that 68% of people taking semaglutide or liraglutide for weight loss stopped within a year.

That population may have stopped for a variety of reasons, including side effects, cost coupled with lack of insurance coverage, or simply shortages of the medications. Whatever the reason, when prescribing one of these drugs to a patient, keep in mind their likelihood of adherence, as it may affect the choice of what to prescribe.

In the study above, 4.5% of users stopped the drugs due to side effects. A different study showed that 7% of people taking once-weekly semaglutide stopped within a year because of the side effects.

The side effects that many people cite as their reason for quitting are digestive ones, including nausea, vomiting, and upset stomach. For example, nausea occurs in about 44% of people taking semaglutide, followed by diarrhea (30%), vomiting (24%), constipation (24%), stomach-area pain (20%), feeling bloated (7%), heartburn (5%), belching or gas (6%).

Side Effects of Common Weight Loss Medications

Here will look at the side effects of phentermine with and without topiramate, naltrexone-bupropion, liraglutide, semaglutide, orlistat, and tirzepatide. For complete information on each individual drug, please consult the manufacturer’s website.

1. Phentermine

The oldest and most widely used weight loss medication is phentermine. It has been around since 1959 and has been used in combination with topiramate since the 1990s.

Phentermine works at the brain level to decrease hunger. This medication is not appropriate for those with hyperthyroidism, glaucoma, or heart disease or who have had a stroke.

Side effects include headache, overstimulation, high blood pressure, insomnia, rapid or irregular heart rate, and tremor. Interactions may occur during or within 14 days following the use of monoamine oxidase (MAO) inhibitors, sympathomimetics, alcohol, adrenergic neuron-blocking drugs, and possibly some anesthetic agents.

2. Phentermine combined with topiramate

Phentermine combined with topiramate cannot be taken during pregnancy. The benefit of this combination is that two medications are working together to decrease hunger and increase fullness.

Side effects of taking phentermine-topiramate include abnormal sensations, dizziness, altered taste, insomnia, constipation, and dry mouth. Contraindications include uncontrolled hypertension and coronary artery disease, hyperthyroidism, glaucoma, and sensitivity to stimulants.

3. Naltrexone-bupropion

Naltrexone-bupropion is another combination medication that can help with fullness and cravings. A person should not take this medication if they have a seizure disorder or take opioids for chronic pain.

The most common side effects include nausea, constipation, headache, vomiting, dizziness, insomnia, dry mouth, and diarrhea.

4 & 5. Liraglutide and semaglutide

Liraglutide and semaglutide are both injectable, although oral forms of both are approved to treat type 2 diabetes. Liraglutide is injected daily and semaglutide, weekly. They both increase satiety or fullness.

Side effects of taking liraglutide include nausea, diarrhea, constipation, vomiting, headache, decreased appetite, dyspepsia, fatigue, dizziness, abdominal pain, increased lipase, renal insufficiency, and increased heart rate.

Gastrointestinal issues are the most common complaint among people who are just starting semaglutide. For this reason, many patients start at a lower dose and work up to their eventual dose. Other side effects can include fatigue, dizziness, headache, belching, bloating or “gassiness,” heartburn, recurrent fever, stomach pain or discomfort, fullness, and yellow eyes or skin.

Headlines have warned of increased suicidal ideation associated with semaglutide. However, a study published in January 2024 in Nature Medicine found that the drug was associated with “a 49% to 73% lower risk of first-time or recurring suicidal ideations compared to other medications for controlling obesity.”

The JAMA study mentioned above compared GLP-1 agonists against naltrexone-bupropion. Researchers concluded that the use of the GLP-1 agonists was associated with an increased risk of pancreatitis, bowel obstruction, and gastroparesis.

Undoubtedly, research on this class of medications will continue rapidly, so it’s a good idea to keep up with the literature.

6. Orlistat

Orlistat is a lipase inhibitor that works by blocking the enzyme that breaks down fats consumed through food, thereby inhibiting the absorption of dietary fats.

The undigested fat is then passed through the body. The most common side effects are oily discharge from the rectum, flatus with discharge, increased defecation, and fecal incontinence.

7. Tirzepatide

Tirzepatide was initially approved to treat type 2 diabetes. In 2023, it was approved for weight loss. As a GLP-1 and GIP receptor agonist, it increases feelings of fullness and helps people maintain a more restrictive diet.

Common side effects include constipation, upset stomach, bloating, and diarrhea. Potential serious side effects also include stomach problems, kidney problems or failure, gallbladder problems, pancreatitis, or hypoglycemia, among others.

Its manufacturer, warns that tirzepatide may cause thyroid tumors or thyroid cancer, so patients should be monitored for symptoms such as swelling in the neck, hoarseness, trouble swallowing, or shortness of breath.

Consider side effects when prescribing weight loss medications

Weight loss medications can be helpful in promoting and maintaining weight loss as part of a comprehensive obesity treatment plan. However, there are side effects, so it’s essential to help patients consider the pros and cons to find the right fit for them.

If you are a patient seeking a doctor with whom to discuss taking weight loss medication, visit our provider directory.

Related Obesity Pillars® Journal Articles

Anti-Obesity Medications and Investigational Agents: An Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) 2022

Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study

Once-weekly semaglutide administered after laparoscopic sleeve gastrectomy: Effects on body weight, glycemic control, and measured nutritional metrics in Japanese patients having both obesity and type 2 diabetes

Leach, Joseph MD, Chief Medical Officer, Prime Therapeutics. Real-World Analysis of Glucagon-Like Peptide-1 Agonist (GLP-1a) Obesity Treatment One Year Cost-Effectiveness and Therapy Adherence. 11 July 2023. Prime Therapeutics.

Sodhi, M., MSc; et al. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. 5 October 2023. 2023;330(18):1795-1797. doi:10.1001/jama.2023.19574

Verovnik B, Vovk A. Semaglutide, suicidal ideation and behaviour: A resting state functional magnetic resonance imaging perspective. Diabetes Obes Metab. 9 Nov 2023. doi: 10.1111/dom.15363. Epub ahead of print. PMID: 37945545.

Wang, W., Volkow, N.D., Berger, N.A. et al. Association of semaglutide with risk of suicidal ideation in a real-world cohort. Nat Med (2024).

John P. H. Wilding D.M, et. al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes, Obesity and Metabolism. 19 April 2022.

Wilding, John P.H., D.M., Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384:989-1002. March 18, 2021. DOI: 10.1056/NEJMoa2032183